A trial with 3'-azido-2',3'-dideoxythymidine and human interferon-α in cats naturally infected with feline leukaemia virus . Feline leukaemia virus ( FeLV ) infection is still one of the leading causes of infection-related deaths in domestic cats . Treatment with various drugs has been attempted , but none has resulted in cure or complete virus elimination . Human interferon-α2a ( huIFN-α2a ) and 3'-azido-2',3'-dideoxythymidine ( AZT ) have been proven to decrease antigenaemia in cats infected experimentally with FeLV . The purpose of this study was to assess the efficacy of huIFN-α2a , AZT and a combination of both drugs in cats infected naturally with FeLV in a placebo-controlled double-blinded trial . Fourty-four FeLV-infected cats in which free FeLV p27 antigen was detected in serum by enzyme-linked immunosorbent assay were included in the study . Cats were assigned to one of four treatment groups that received either high dose huIFN-α2a ( 10 ( 5 ) IU/kg q24h ; 12 cats ) , AZT ( 5 mg/kg q12h ; 10 cats , both of these treatments ( 12 cats ) or placebo ( 10 cats ) . All cats were treated for 6 weeks . Clinical variables , including stomatitis , and laboratory parameters , such as CD4 ( + ) and CD8 ( + ) counts and serum FeLV p 27 antigen concentration , were recorded throughout the treatment period . No significant difference among the groups was observed during the treatment period for any of the parameters . Aside from anaemia in one cat treated with AZT , no adverse effects were observed . It was not possible to demonstrate efficacy of huIFN-α2a or AZT alone or together in cats infected naturally with FeLV when given according to this regimen for 6 weeks ; however , no notable side effects were detected .

efficacy

stomatitis

CD8 ( + ) counts

serum FeLV p 27 antigen concentration

anaemia


Divergence in student and educator conceptual structures during auscultation training . CONTEXT Simulation-based medical education allows trainees to engage in self-regulated learning ( SRL ) , yet research aimed at elucidating the mechanisms of SRL in this context is relatively absent . We compared 'unguided ' SRL with 'directed ' SRL ( DSRL ) , wherein learners followed an expert-designed booklet . METHODS Year 1 medical students ( n = 37 ) were randomly assigned to practise identifying seven cardiac murmurs using a simulator and video only ( SRL group ) or a simulator and video plus the booklet ( DSRL group ) . All participants completed a 22-item test 3 weeks later . To compare interventions , we analysed students ' diagnostic accuracy . As a novel source of evidence , we documented how participants autonomously sequenced the seven murmurs during initial and delayed practice sessions . In addition , we surveyed clinical educators ( n = 17 ) to find out how they would sequence their teaching of these murmurs . RESULTS The DSRL group used 50 % more training time than the SRL group ( p < 0.001 ) . The groups ' diagnostic accuracy , however , did not differ significantly on the post-test , retention test or transfer test items ( p > 0.12 ) . Despite practising with the expert-defined 'timing-based ' approach to murmur diagnosis ( i.e . systolic versus diastolic ) , 84 % of DSRL participants implemented a location-based approach ( i.e . practising aortic murmurs separately from mitral murmurs ) during a second , unguided practice session . Notably , most SRL participants used that same approach spontaneously . By contrast , clinical educators were split in their use of the timing-based ( n = 10 ) and the location-based ( n = 6 ) approaches . Chi-squared analyses suggested educators ' conceptions for organising murmurs differed significantly from students ' conceptions . CONCLUSIONS Contrary to our predictions , directing students ' SRL produced no additional benefit and increased their practice time . Our findings suggest one potential source of these results was a divergence between student and educator conceptions for structuring the practice of cardiac auscultation skills . This phenomenon has not been well articulated in the medical education literature , and may have important implications in many ( especially technology-mediated ) educational contexts .

'unguided ' SRL

'directed ' SRL

simulator and video only ( SRL group )

simulator and video plus the booklet

additional benefit

practice time .

auscultation training

n = 37


Effect of aliskiren on proteinuria in non-diabetic chronic kidney disease : a double-blind , crossover , randomised , controlled trial . AIM To evaluate the proteinuria-lowering effect of a renin inhibitor ( aliskiren ) , compared to placebo and to an angiotensin-converting enzyme inhibitor ( perindopril ) , in patients with non-diabetic chronic kidney disease . METHODS A randomised , double-blind , crossover trial was performed in 14 patients with nondiabetic chronic kidney disease with 24-h mean proteinuria of 2.01 g ( 95 % CI , 1.36–2.66 ) and estimated creatinine clearance of 93±6.8 ml/min . The study consisted of five treatment periods . The patients were randomly assigned to receive aliskiren ( 150 mg ) , aliskiren ( 300 mg ) , perindopril ( 5 mg ) , perindopril ( 10 mg ) or placebo . RESULTS Aliskiren and perindopril reduced proteinuria . These effects were dose-dependent . Furthermore , 24-h proteinuria was reduced by 23 % ( mean 95 % CI ; 2–44 ) by treatment with aliskiren ( 150 mg ) , by 36 % ( 95 % CI , 17–55 ; P < 0.001 ) with aliskiren ( 300 mg ) , by 7.1 % ( 95 % CI , 11–26 ) with perindopril ( 5 mg ) and by 25 % ( 95 % CI , 11–39 ; P < 0.05 ) with perindopril ( 10 mg ) , compared to placebo . No significant difference was found between the effects of aliskiren and perindopril . CONCLUSIONS Aliskiren significantly reduced proteinuria . The antiproteinuric effect is probably similar to that of perindopril , for equivalent hypotensive dosages . The renin inhibitor provides a promising alternative approach for the treatment of patients with chronic proteinuric non-diabetic kidney disease .

aliskiren

renin inhibitor

aliskiren

placebo

angiotensin-converting enzyme inhibitor

perindopril

proteinuria

proteinuria-lowering effect

proteinuria

proteinuria

antiproteinuric

non-diabetic chronic kidney disease

nondiabetic chronic kidney disease

chronic proteinuric non-diabetic kidney


Are tyrosine kinase inhibitors still active in patients with metastatic renal cell carcinoma previously treated with a tyrosine kinase inhibitor and everolimus ? Experience of 36 patients treated in France in the RECORD-1 Trial . BACKGROUND Because the response to treatment is limited , patients with metastatic renal cell carcinoma ( mRCC ) typically receive multiple treatments . Guidelines recommend everolimus for patients previously treated with tyrosine kinase inhibitors ( TKI ) sunitinib or sorafenib . This study evaluated the efficacy of TKI re-treatment in patients with disease progression after a TKI-everolimus sequence . PATIENTS AND METHODS Data were reviewed for patients enrolled in RECORD-1 ( Renal Cell Cancer Treatment With Oral RAD001 Given Daily ) at French sites . Response , progression-free survival ( PFS ) , and overall survival were evaluated in patients treated with a TKI-everolimus-TKI sequence . RESULTS Thirty-six patients received a TKI after everolimus : sunitinib in 17 patients , sorafenib in 15 , and dovitinib ( TKI258 ) in 4 . The response rate with TKI re-treatment was 8 % , and the disease-control rate ( response plus stable disease ) was 75 % . The median PFS with each component of the TKI-everolimus-TKI sequence was 10.7 months ( 95 % CI , 1.8-28.5 months ) , 8.9 months ( 95 % CI , 1.7-34.6 months ) , and 8.2 months ( 95 % CI , 5.2-11.9 months ) , respectively . The median overall survival from the start of everolimus was 29.1 months ( 95 % CI 21.1 to not reached months ) , which suggests a benefit in using TKI in this setting . CONCLUSIONS Administration of a TKI-everolimus-TKI sequence may be associated with clinical benefit and should be prospectively investigated .

tyrosine kinase inhibitors

tyrosine kinase inhibitor

everolimus

everolimus

sorafenib

TKI

TKI-everolimus sequence

TKI-everolimus-TKI sequence

TKI

everolimus

sunitinib

sorafenib

dovitinib

TKI

TKI-everolimus-TKI

everolimus

TKI

TKI-everolimus-TKI sequence

efficacy

Response

response rate

median PFS

median overall survival

clinical benefit

Thirty-six


Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease : a phase I , randomized , placebo-controlled , double-blind , dose-escalation study . OBJECTIVES Ponezumab is a humanized antiamyloid beta ( Aβ ) monoclonal antibody designed to treat Alzheimer disease ( AD ) . METHODS This randomized , double-blind , single-dose-escalation study evaluated the safety , pharmacokinetics , and pharmacodynamics of 0.1 , 0.3 , 1 , 3 , and 10 mg/kg ponezumab ( n = 4 , 4 , 4 , 6 , and 8 , respectively ) versus placebo ( n = 11 ) after a 2-hour intravenous infusion in subjects with mild-to-moderate AD . Cerebrospinal fluid ( CSF ) samples were obtained from the 1- and 10-mg/kg groups at baseline and at day 29 . The subjects were followed for 1 year . RESULTS All subjects completed the trial . Ponezumab was well tolerated with no drug-attributed serious adverse events . The most common adverse events were upper respiratory tract infection , headache , and back pain , all mild to moderate . One subject ( 10 mg/kg ) experienced a mild hypersensitivity reaction . Another subject ( 0.1 mg/kg ) demonstrated slight enlargement of a preexisting midbrain lesion . Electrocardiography and laboratory values ( including CSF ) were unremarkable . No evidence of new microhemorrhage , vasogenic edema , or meningoencephalitis was noted . Plasma maximum observed concentration increased approximately dose proportionally , and the area under the plasma concentration-time profile from time zero extrapolated to infinite time ( AUC ( inf ) ) increased slightly more than dose proportionally . Mean terminal half-life was approximately 6 weeks . Two subjects ( 10 mg/kg ) had measurable CSF ponezumab concentrations ( ~0.5 % of plasma values ) at day 29 . Plasma Aβ ( 1-x ) and Aβ ( 1-40 ) increased dose dependently , and mean CSF Aβ ( 1-x ) increased 38 % from baseline with 10 mg/kg ( P = 0.002 vs placebo ) . CONCLUSIONS A 2-hour infusion of 0.1 to 10 mg/kg ponezumab was well tolerated in subjects with mild-to-moderate AD . Plasma pharmacokinetic profile was approximately linear . Plasma Aβ increased with dose , and CSF Aβ increased at the highest dose , suggesting that intravenous ponezumab alters central Aβ levels .

ponezumab

placebo-controlled

Ponezumab

tolerated

mild hypersensitivity reaction

CSF ponezumab concentrations

mild-to-moderate Alzheimer disease


[ Antiinflammatory potential of seven plant extracts in the ultraviolet erythema test . A randomized , placebo-controlled study ] . BACKGROUND Phytotherapeutics are widely used in medicine . The aim of this study was the evaluation of the antiinflammatory potential of seven medical plant extracts using the ultraviolet- ( UV ) -erythema test . PATIENTS AND METHODS Randomized , placebo-controlled study on 40 healthy subjects . Test areas on the upper back were irradiated with the 1.5 fold UV-B minimal erythema dose ( MED ) . Formulations of Aloe vera , Chamomilla recutita , Hamamelis virginiana , Melissa officinalis , Mentha arvensis , Melaleuca alternifolia , Coriandrum sativum as well as 1 % hydrocortisone acetate and 0.1 % betamethasone valerate as positive controls and unguentum leniens as vehicle control were applied under occlusion on the irradiated areas and on non-irradiated area on the contralateral side . Photometric assessment of the erythema was performed before the application of the substances ( t0 ) , at 24 h ( t1 ) and at 48 h ( t2 ) . RESULTS Aloe vera , Chamomilla recutita , Melissa officinalis , Melaleuca alternifolia and Coriandrum sativum showed an antiinflammatory effect compared to UV-control and unguentum leniens . However , the results were only statistically significant for Aloe vera . All tested plant extracts were well tolerated . CONCLUSION Aloe vera possesses an antiinflammatory effect on UV-induced erythemas .

seven plant extracts

placebo-controlled

seven medical plant extracts

placebo-controlled

1.5 fold UV-B minimal erythema dose

Aloe vera

Chamomilla recutita

Hamamelis virginiana

Melissa officinalis

Mentha arvensis

Melaleuca alternifolia

Coriandrum sativum

1 % hydrocortisone acetate

0.1 % betamethasone valerate

unguentum leniens

tolerated

healthy


A pilot randomised controlled trial of cognitive behavioural therapy for antenatal depression . BACKGROUND Few trials have evaluated the effectiveness of psychological treatment in improving depression by the end of pregnancy . This is the first pilot randomised controlled trial ( RCT ) of individual cognitive behavioural therapy ( CBT ) looking at treating depression by the end of pregnancy . Our aim was to assess the feasibility of delivering a CBT intervention modified for antenatal depression during pregnancy . METHODS Women in North Bristol , UK between 8-18 weeks pregnant were recruited through routine contact with midwives and randomised to receive up to 12 sessions of individual CBT in addition to usual care or to continue with usual care only . Women were eligible for randomisation if they screened positive on a 3-question depression screen used routinely by midwives and met ICD-10 criteria for depression assessed using the clinical interview schedule - revised version ( CIS-R ) . Two CBT therapists delivered the intervention . Follow-up was at 15 and 33 weeks post-randomisation when assessments of mental health were made using measures which included the CIS-R . RESULTS Of the 50 women assessed for the trial , 36 met ICD-10 depression criteria and were randomised : 18 to the intervention and 18 to usual care . Thirteen of the 18 ( 72 % ) women who were allocated to receive the intervention completed 9 or more sessions of CBT before the end of pregnancy . Follow-up rates at 15 and 33 weeks post-randomisation were higher in the group who received the intervention ( 89 % vs. 72 % at 15 weeks and 89 % vs. 61 % at 33 weeks post-randomisation ) . At 15 weeks post-randomisation ( the end of pregnancy ) , there were more women in the intervention group ( 11/16 ; 68.7 % ) who recovered ( i.e . no longer met ICD-10 criteria for depression ) , than those receiving only usual care ( 5/13 ; 38.5 % ) . CONCLUSIONS This pilot trial shows the feasibility of conducting a large RCT to assess the effectiveness of CBT for treating antenatal depression before the end of pregnancy . The intervention could be delivered during the antenatal period and there was some evidence to suggest that it could be effective . TRIAL REGISTRATION ISRCTN44902048 .

cognitive behavioural therapy

CBT intervention

of mental health

criteria for depression


Effects of coronary sinus occlusion on myocardial ischaemia in humans : role of coronary collateral function . OBJECTIVE This study tested the hypotheses that intermittent coronary sinus occlusion ( iCSO ) reduces myocardial ischaemia , and that the amount of ischaemia reduction is related to coronary collateral function . DESIGN Prospective case-control study with intraindividual comparison of myocardial ischaemia during two 2-min coronary artery balloon occlusions with and without simultaneous iCSO by a balloon-tipped catheter . SETTING University Hospital . PATIENTS 35 patients with chronic stable coronary artery disease . INTERVENTION 2-min iCSO . MAIN OUTCOME MEASURES Myocardial ischaemia as assessed by intracoronary ( i.c . ) ECG ST shift at 2 min of coronary artery balloon occlusion . Collateral flow index ( CFI ) without iCSO , that is , the ratio between mean distal coronary occlusive ( Poccl ) and mean aortic pressure ( Pao ) both minus central venous pressure . RESULTS I.c . ECG ST segment shift ( elevation in all ) at the end of the procedure with iCSO versus without iCSO was 1.33±1.25 mV versus 1.85±1.45 mV , p < 0.0001 . Regression analysis showed that the degree of i.c . ECG ST shift reduction during iCSO was related to CFI , best fitting a Lorentzian function ( r ( 2 ) =0.61 ) . Ischaemia reduction with iCSO was greatest at a CFI of 0.05-0.20 , whereas in the low and high CFI range the effect of iCSO was absent . CONCLUSIONS ICSO reduces myocardial ischaemia in patients with chronic coronary artery disease . Ischaemia reduction by iCSO depends on coronary collateral function . A minimal degree of collateral function is necessary to render iCSO effective . ICSO can not manifest an effect when collateral function prevents ischaemia in the first place .

2-min iCSO .

myocardial ischaemia

ischaemia

Myocardial ischaemia

intracoronary ( i.c . ) ECG ST shift

ECG ST segment shift


Influence of Aloe arborescens Mill . extract on selected parameters of pro-oxidant-antioxidant equilibrium and cytokine synthesis in rowers . This investigation examined the effect of supplementation with Biostimine , extract from Aloe arborescens Mill . leaves , on the levels of pro-oxidant-antioxidant equilibrium markers and anti- and proinflammatory cytokines in rowers subjected to exhaustive exercise . This double-blind study included 18 members of the Polish Rowing Team . Subjects were randomly assigned to the supplemented group ( n = 9 ) , which received one ampoule of Biostimine once daily for 4 weeks , or to the placebo group ( n = 9 ) . Subjects performed a 2,000-meter-maximum test on a rowing ergometer at the beginning and end of the preparatory camp . Blood samples were obtained from the antecubital vein before each exercise test , 1 min after completing the test and after a 24-hr recovery period . Superoxide dismutase and glutathione peroxidase activity as well as the concentration of thiobarbituric acid reactive substances ( TBARS ) were assessed in erythrocytes . In addition , total antioxidant capacity ( TAC ) and creatine kinase activity were measured in plasma samples , and cytokine ( IL-6 , IL-10 ) concentrations were determined in the serum . Before and after Biostimine supplementation , exercise significantly increased the values of SOD , IL-6 , IL-10 , and TBARS in both groups . However , postexercise and recovery levels of TBARS were significantly lower in athletes receiving Biostimine than in controls . After supplementation , TAC was the only variable with the level being significantly higher in the supplemented group than in the placebo group . Consequently , we can conclude that Biostimine supplementation reduces the postexercise level of TBARS by increasing the antioxidant activity of plasma but has no effect on inflammatory markers .

Aloe arborescens Mill . extract

Biostimine

placebo

Biostimine supplementation

Biostimine

placebo

Biostimine supplementation

pro-oxidant-antioxidant equilibrium

cytokine synthesis

proinflammatory cytokines

total antioxidant capacity ( TAC )

creatine kinase activity

TBARS

TAC

TBARS

antioxidant activity of plasma

inflammatory markers

rowers .


Influence of SNPs in nutrient-sensitive candidate genes and gene-diet interactions on blood lipids : the DiOGenes study . Blood lipid response to a given dietary intervention could be determined by the effect of diet , gene variants or gene-diet interactions . The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet , among overweight European adults participating in the Diet Obesity and Genes study . By multiple linear regressions , 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP-diet interaction effects on total cholesterol , LDL-cholesterol , HDL-cholesterol and TAG after an 8-week low-energy diet ( only main effect ) , and a 6-month ad libitum weight maintenance diet , with different contents of dietary protein or glycaemic index . After adjusting for multiple testing , a SNP-dietary protein interaction effect on TAG was identified for lipin 1 ( LPIN1 ) rs4315495 , with a decrease in TAG of 20.26 mmol/l per A-allele/protein unit ( 95 % CI 20.38 , 20.14 , P=0.000043 ) . In conclusion , we investigated SNP-diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes , selected for their involvement in lipid metabolism pathways , and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration .

given dietary intervention

given diet

8-week low-energy diet

dietary protein

glycaemic index

SNP-diet interactions

blood lipids

Blood lipid

lipid profile

decrease in TAG

DiOGenes study .

overweight

Diet Obesity and Genes study


Temporal expectation in focal hand dystonia . Patients with writer 's cramp present sensory and representational abnormalities relevant to motor control , such as impairment in the temporal discrimination between tactile stimuli and in pure motor imagery tasks , like the mental rotation of corporeal and inanimate objects . However , only limited information is available on the ability of patients with dystonia to process the time-dependent features ( e.g . speed ) of movement in real time . The processing of time-dependent features of movement has a crucial role in predicting whether the outcome of a complex motor sequence , such as handwriting or playing a musical passage , will be consistent with its ultimate goal , or results instead in an execution error . In this study , we sought to evaluate the implicit ability to perceive the temporal outcome of different movements in a group of patients with writer 's cramp . Fourteen patients affected by writer 's cramp in the right hand and 17 age- and gender-matched healthy subjects were recruited for the study . Subjects were asked to perform a temporal expectation task by predicting the end of visually perceived human body motion ( handwriting , i.e . the action performed by the human body segment specifically affected by writer 's cramp ) or inanimate object motion ( a moving circle reaching a spatial target ) . Videos representing movements were shown in full before experimental trials ; the actual tasks consisted of watching the same videos , but interrupted after a variable interval ( 'pre-dark ' ) from its onset by a dark interval of variable duration . During the 'dark ' interval , subjects were asked to indicate when the movement represented in the video reached its end by clicking on the space bar of the keyboard . We also included a visual working memory task . Performance on the timing task was analysed measuring the absolute value of timing error , the coefficient of variability and the percentage of anticipation responses . Patients with writer 's cramp exhibited greater absolute timing error compared with control subjects in the human body motion task ( whereas no difference was observed in the inanimate object motion task ) . No effect of group was documented on the visual working memory tasks . Absolute timing error on the human body motion task did not significantly correlate with symptom severity , disease duration or writing speed . Our findings suggest an alteration of the writing movement representation at a central level and are consistent with the view that dystonia is not a purely motor disorder , but it also involves non-motor ( sensory , cognitive ) aspects related to movement processing and planning .

temporal outcome

temporal expectation task

Videos representing movements

visual working memory task

Absolute timing error

focal hand dystonia

writer 's cramp

dystonia

writer 's cramp

Fourteen

writer 's cramp


Contribution of endogenous bradykinin to fibrinolysis , inflammation , and blood product transfusion following cardiac surgery : a randomized clinical trial . Bradykinin increases during cardiopulmonary bypass ( CPB ) and stimulates the release of nitric oxide , inflammatory cytokines , and tissue-type plasminogen activator ( t-PA ) , acting through its B2 receptor . This study tested the hypothesis that endogenous bradykinin contributes to the fibrinolytic and inflammatory response to CPB and that bradykinin B2 receptor antagonism reduces fibrinolysis , inflammation , and subsequent transfusion requirements . Patients ( N = 115 ) were prospectively randomized to placebo , ε-aminocaproic acid ( EACA ) , or HOE 140 , a bradykinin B2 receptor antagonist . Bradykinin B2 receptor antagonism decreased intraoperative fibrinolytic capacity as much as EACA , but only EACA decreased D-dimer formation and tended to decrease postoperative bleeding . Although EACA and HOE 140 decreased fibrinolysis and EACA attenuated blood loss , these treatments did not reduce the proportion of patients transfused . These data suggest that endogenous bradykinin contributes to t-PA generation in patients undergoing CPB , but that additional effects on plasmin generation contribute to decreased D-dimer concentrations during EACA treatment .

fibrinolysis

inflammation

blood product transfusion

following cardiac surgery :

cardiopulmonary bypass ( CPB )

Patients ( N = 115 )


Effects of a dietetic treatment in older , undernourished , community-dwelling individuals in primary care : a randomized controlled trial . PURPOSE Undernutrition is a prevalent problem in older , community-dwelling individuals . Aim of this study was to determine the effects of a dietetic treatment in older , undernourished , community-dwelling individuals . METHODS A parallel randomized controlled trial was performed in 146 non-institutionalized , undernourished individuals aged ≥65 years in primary care . Participants were randomly assigned to the intervention ( referral to and treatment by a trained dietitian ) or control group ( no referral ) . Body weight , physical performance , handgrip strength , energy intake , protein intake and fat-free mass were assessed at baseline , after 3 months and after 6 months . RESULTS All randomized participants ( n = 146 ) were included in the intention-to-treat generalized estimating equations analysis ( 72 in intervention and 74 in control group ) . No treatment effect was found on the primary outcomes body weight ( β = 0.49 kg , 95 % CI : -0.15-1.12 ) , physical performance ( β = 0.15 points , 95 % CI : -0.33-0.64 ) and handgrip strength ( β = 0.49 kg , 95 % CI : -0.62-1.60 ) . Furthermore , no treatment effect was found for the secondary outcomes . Predefined subgroup analyses showed a treatment effect on body weight in physically active participants ( β = 1.25 kg , 95 % CI : 0.70-2.11 ) and not in inactive participants ( β = -0.20 kg , 95 % CI : -1.16-0.75 ) . CONCLUSIONS After 6 months , a dietetic treatment by trained dietitians does not lead to increases in body weight and physical functioning in older , undernourished , community-dwelling individuals .

dietetic treatment

dietetic treatment

Body weight

physical performance

handgrip strength

older

undernourished

undernourished

non-institutionalized , undernourished

aged ≥65 years


Design and development of a Virtual Dolphinarium for children with autism . The recent proliferation of virtual reality ( VR ) technology applications in the autism therapy to promote learning and positive behavior among such children has produced optimistic results in developing a variety of skills and abilities in them . Dolphin-assisted therapy has also become a topic of public and research interest for autism intervention and treatment . This paper will present an innovative design and development of a Virtual Dolphinarium for potential autism intervention . Instead of emulating the swimming with dolphins , our virtual dolphin interaction program will allow children with autism to act as dolphin trainers at the poolside and to learn ( nonverbal ) communication through hand gestures with the virtual dolphins . Immersive visualization and gesture-based interaction are implemented to engage children with autism within an immersive room equipped with a curved screen spanning a 320 ( ° ) and a high-end five-panel projection system . This paper will also report a pilot study to establish trial protocol of autism screening to explore the participants ' readiness for the virtual dolphin interaction . This research will have two potential benefits in the sense of helping children with autism and protecting the endangered species .

Virtual Dolphinarium

Dolphin-assisted therapy

Virtual Dolphinarium

Immersive visualization

gesture-based interaction


Supplementation with n3 fatty acid ethyl esters increases large and small artery elasticity in obese adults on a weight loss diet . Increased arterial stiffness is associated with enhanced risk of cardiovascular disease in obese individuals . Whether n3 fatty acid ethyl ester ( FAEE ) supplementation improves arterial stiffness in obese participants on a weight loss diet has not yet been investigated . The objective of the study was to carry out a 12-wk randomized , single-blind trial to test the effect of a 25 % energy deficit weight loss diet alone ( WL ) ( n = 12 ) or WL plus 4 g/d Omacor ( 46 % EPA and 38 % DHA ) supplementation ( WL+FAEE ) ( n = 13 ) on arterial elasticity in obese adults . Large ( C1 ) and small artery elasticity ( C2 ) were measured by pulse contour analysis of the radial artery . WL alone reduced ( P < 0.05 in all ) body weight ( -3 % ) , waist circumference ( -4 % ) , systolic ( -3 % ) and diastolic ( -3 % ) blood pressures , cardiac output ( -4 % ) , plasma TG concentration ( -25 % ) , and the homeostasis model assessment ( HOMA ) score ( -12 % ) and increased plasma HDL cholesterol ( +9 % ) and adiponectin ( +18 % ) concentrations . However , WL alone did not alter C1 and C2 . The WL+FAEE intervention significantly reduced body weight ( -4 % ) , waist circumference ( -4 % ) , systolic ( -8 % ) and diastolic ( -5 % ) blood pressures , pulse pressure ( -5 % ) , heart rate ( -8 % ) , plasma TG concentration ( -36 % ) , and HOMA score ( -12 % ) and increased stroke volume ( +3 % ) , plasma HDL cholesterol ( +6 % ) and adiponectin concentrations ( +28 % ) , and C1 ( +20 % ) and C2 ( +22 % ) artery elasticity . The changes in systolic blood pressure , heart rate , plasma TGs , C1 , and C2 were significantly greater in the WL+FAEE group than in the WL group . Supplementation with n3 FAEEs improves C1 and C2 independently of weight loss in obese adults .

n3 fatty acid ethyl esters

energy deficit weight loss diet

WL

plus 4 g/d Omacor

46 % EPA

38 % DHA ) supplementation ( WL+FAEE )

WL

WL+FAEE intervention

WL+FAEE

WL

n3 FAEEs

body weight

increased plasma HDL cholesterol

systolic

diastolic

pulse pressure

plasma TG concentration

increased stroke volume

systolic blood pressure

heart rate

plasma TGs

weight loss

obese adults on a weight loss diet .

obese adults .


[ Afala in the treatment of patients with BPH : efficacy and safety ] . The double-blind , placebo-controlled , randomized clinical trial involving 94 patients has evaluated the efficacy and safety of domestic preparation afala in patients with symptoms of I-II stages benign prostatic hyperplasia ( BPH ) . It was shown that a 6-month course of treatment with afala at a dose of 2 tablets 4 times a day resulted in a significant reduction in the severity of urinary disorders , estimated by total IPSS score , relative to baseline values and compared to placebo therapy . The most pronounced therapeutic effects of the drug were registered in respect of irritative symptoms of BPH . According uroflowmetry , peak flow rate after 6 months of treatment was increased by more than 50 % . Significant clinical benefit persisted not only within the 6-month course of therapy , but 3 months after . Long-term therapy had no effect on the concentration of total , free and complex PSA , testosterone ( total and free ) , dihydrotestosterone , and prolactin in the blood . Absence of adverse effects , biochemical abnormalities , changes in clinical blood and urine confirmed the safety of 6-month therapy .

[ Afala

placebo-controlled

afala

placebo

peak flow rate after

prolactin in the blood .

BPH


Pretreatment and co-administration of oral anti-diabetic agent with clomiphene citrate or rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome . AIM The objective of this study was to explore the result of pretreatment and concomitant use of metformin with clomiphene citrate ( CC ) and rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS This randomized controlled trial was done in the Dhaka Medical College and Hospital and the Infertility Care and Research Centre , Dhaka , Bangladesh . A total of 165 infertile patients with CC-resistant PCOS who attended for treatment were the target population for this study . Patients were divided into three groups : groups A and B were given metformin and group C was the control . Along with metformin , group A received CC and group B received rFSH . Group C was treated with only rFSH . Metformin was given 1500 mg daily for 4 weeks . Afterwards CC or rFSH were added for induction of ovulation along with metformin . Six ovulatory cycles were assessed . Treatment was terminated when there was no response with maximum dose of CC and rFSH or after six ovulatory cycles without pregnancy or after achieving pregnancy . A P-value of < 0.5 was considered as significant . RESULTS Ovulation ( 89.09 % ) and pregnancy ( 54.55 % ) rates were higher in group B. Ovulation ( 74.55 % ) and pregnancy ( 29.09 % ) rates were also satisfactory in group C but a dose of rFSH requirement was significantly higher ( P = 0.000 ) . In group A , both ovulation and pregnancy rate were much lower than the other two groups ( 27.27 % and 12.73 % , respectively ) . CONCLUSIONS Use of metformin increases the response of ovulation-inducing agents and can be used safely in PCOS .

oral anti-diabetic agent

clomiphene citrate

rFSH

metformin

clomiphene citrate ( CC )

rFSH

metformin

control .

metformin

CC

rFSH .

rFSH . Metformin

CC

rFSH

CC

rFSH

rFSH

pregnancy


Practice makes improvement : how adults with autism out-perform others in a naturalistic visual search task . People with autism spectrum disorder ( ASD ) often exhibit superior performance in visual search compared to others . However , most studies demonstrating this advantage have employed simple , uncluttered images with fully visible targets . We compare the performance of high-functioning adults with ASD and matched controls on a naturalistic luggage screening task . Although the two groups were equally accurate in detecting targets , the ASD adults improve in their correct elimination of target-absent bags faster than controls . This feature of their behavior is extremely important for many real-world monitoring tasks that require sustained attention for long time periods . Further analyses suggest that this improvement is attributable neither to the motor speed nor to the level of intelligence of the adults with ASD . These findings may have possible implications for employment opportunities of adult individuals with ASD .

naturalistic luggage screening task .

correct elimination of target-absent

adults

autism

autism spectrum disorder ( ASD )

adults

ASD

ASD

adults

adults

ASD

adult

ASD


Drug-drug interaction study of ACT-178882 , a new renin inhibitor , and diltiazem in healthy subjects . BACKGROUND AND OBJECTIVE The cytochrome P450 ( CYP ) enzyme , CYP3A4 , metabolizes ACT-178882 , a new direct renin inhibitor . This study investigated the effect of diltiazem , a moderate inhibitor of CYP3A4 , on the single-dose pharmacokinetics of ACT-178882 in healthy subjects . METHODS In this open-label , two-way crossover , drug-drug interaction study , healthy young male subjects received treatments A and B in a randomized fashion . Treatment A consisted of a single dose of 100 mg ACT-178882 and treatment B of diltiazem 300 mg once a day for 13 days and a single dose of 100 mg ACT-178882 on day 4 . Serial blood samples for the measurement of ACT-178882 were drawn pre-dose and up to 120 h post-dose during treatment A and pre-dose ACT-178882 and up to 240 h post-dose during treatment B. Trough blood samples for the measurement of diltiazem were taken on days 1-5 of dosing during treatment B . Safety was assessed by recording of vital signs and electrocardiogram , clinical laboratory tests and adverse event reporting . RESULTS Fourteen subjects were enrolled and completed the study . In the absence of diltiazem , the mean ( 95 % confidence interval [ CI ] ) maximum concentration ( Cmax ) and area under the curve from time zero to infinity ( AUC∞ ) were 26.8 ( 20.1-35.8 ) ng/mL and 454 ( 351-587 ) ng·h/mL , respectively . In the presence of diltiazem these values were 43.5 ( 36.8-51.4 ) ng/mL and 918 ( 781-1078 ) ng·h/mL , respectively . The median time to Cmax ( tmax ) for ACT-178882 was prolonged from 3.5 to 5.0 h by diltiazem whereas its apparent terminal half-life ( t½ ) was unaffected by diltiazem , 22.9 and 24.2 h for treatments A and B , respectively . Using treatment A as reference , the geometric mean ratio ( 90 % CI ) was 1.62 ( 1.36-1.94 ) for Cmax and 2.02 ( 1.75-2.34 ) for AUC∞ , indicating a significant interaction between ACT-178882 and diltiazem . One ( 7.1 % ) and 3 ( 21.3 % ) of 14 subjects reported an adverse event during treatment A and B , respectively , with headache being the most frequently reported , with three events . There were no clinically relevant effects of treatments on vital signs , electrocardiogram or clinical laboratory variables . CONCLUSION Concomitant administration of diltiazem doubled the exposure to ACT-178882 without affecting t½ . The clinical significance of this increase is at present unknown and will need to be investigated in future clinical studies . Treatment with ACT-178882 alone or in combination with diltiazem was safe and well tolerated .

diltiazem

diltiazem

effect

healthy

healthy

healthy

young

male


Wheelchair skills training to improve confidence with using a manual wheelchair among older adults : a pilot study . OBJECTIVE To examine the effects of wheelchair skills training on confidence in older adults who are inexperienced wheelchair users . DESIGN Parallel group , single-blind randomized controlled trial . SETTING Research laboratory in a rehabilitation hospital . PARTICIPANTS Participants ( N=20 ) who were community-living older adults at least 65 years old ( mean age , 70y ) , 50 % women , and who had no experience of using a wheelchair were randomly allocated to an intervention ( n=10 ) or control ( n=10 ) group . INTERVENTIONS The intervention group received two 1-hour training sessions that followed the Wheelchair Skills Training Program ( WSTP ) protocol . The control group received a single socialization contact . MAIN OUTCOME MEASURE The Wheelchair Use Confidence Scale-Manual ( WheelCon-M ) was used to evaluate confidence with using a manual wheelchair . The WheelCon-M is a self-report questionnaire that comprises 65 items in 6 conceptual areas . RESULTS A 1-way between-groups analysis of covariance revealed a significant difference in postintervention WheelCon-M scores between the intervention and control groups ( F1,17=10.9 , P=.004 ) after controlling for baseline WheelCon-M scores . A large effect size was also observed ( partial η ( 2 ) =.39 ) . Secondary analyses revealed that the WSTP had greater effects on confidence in areas related to maneuvering around the physical environment , knowledge and problem solving , advocacy , and managing emotions than in areas related to performing activities and behaving in social situations . CONCLUSION Two 1-hour WSTP sessions improve confidence with using a manual wheelchair among older adults who are inexperienced wheelchair users .

Wheelchair skills training

wheelchair skills training

single socialization contact

confidence

confidence

evaluate confidence

significant difference

postintervention WheelCon-M scores

effect size

older adults

older adults

inexperienced wheelchair users

older adults at least 65 years old

women


Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma : correlative analysis from a large North American cooperative group trial . Epstein-Barr virus ( EBV ) is associated with Hodgkin lymphoma ( HL ) and can be detected by in situ hybridization ( ISH ) of viral nucleic acid ( EBER ) in tumor cells . We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL . Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH . A cutoff of > 60 viral copies/100 µL plasma yielded 96 % concordance with EBER-ISH . Pretreatment and month 6 plasma specimens were designated EBV ( - ) or EBV ( + ) by this cutoff . Patients with pretreatment EBV ( + ) plasma ( n = 54 ) had inferior failure-free survival ( FFS ) compared with those with pretreatment EBV ( - ) plasma ( n = 274 ) , log-rank P = .009 . By contrast , no difference in FFS was observed when patients were stratified by EBER-ISH . Pretreatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses . At month 6 , plasma EBV ( + ) patients ( n = 7 ) had inferior FFS compared with plasma EBV ( - ) patients ( n = 125 ) , log-rank P = .007 . These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility both at baseline and after therapy . This trial was registered at www.clinicaltrials.gov as # NCT00003389 .

EBV tumor status

by

EBER-ISH

EBER-ISH

tumor status

EBER-ISH

advanced Hodgkin lymphoma


A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection : analysis of week 96 results . We report week 96 results from a phase 3 trial of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate ( EVG/COBI/FTC/TDF , n = 348 ) vs efavirenz/emtricitabine/tenofovir disoproxil fumarate ( EFV/FTC/TDF , n = 352 ) . At week 48 , EVG/COBI/FTC/TDF was noninferior to EFV/FTC/TDF ( 88 % vs 84 % , difference +3.6 % , 95 % confidence interval : -1.6 % to 8.8 % ) . Virologic success ( HIV-1 RNA < 50 copies/mL ) was maintained at week 96 ( 84 % vs 82 % , difference +2.7 % , 95 % CI : -2.9 % to 8.3 % ) . Discontinuation due to adverse events was low ( 5 % vs 7 % ) . Median changes in serum creatinine ( mg/dL ) at week 96 were similar to week 48 . These results support the durable efficacy and long-term safety of EVG/COBI/FTC/TDF .

EVG/COBI/FTC/TDF

EFV/FTC/TDF

EVG/COBI/FTC/TDF

Virologic success

Discontinuation due to adverse events

Median changes in serum creatinine

durable efficacy

long-term safety

HIV-1 infection :

n = 352


Antihistamines do not inhibit the wheal induced by the intradermal injection of autologous serum in resistant chronic idiopathic urticaria . Some patients with chronic idiopathic urticaria ( CIU ) are resistant to conventional doses of antihistamines ( AHs ) . This study was designed to check whether the skin wheal and flare reaction produced by the intradermal injection of autologous serum ( AS ) and by histamine differs in AH-resistant and AH responder CIU patients . CIU patients with treatment failure under fexofenadine at 180 mg q.d . increased their daily dose of AH to 4 tablets daily . Those with significant improvement of urticaria activity score under fexofenadine at 180 mg were included in the CIU group . Subjects with treatment failure despite a full 8-week fourfold fexofenadine treatment were included in the resistant CIU ( R-CIU group ) . The control group consisted of sex- and age-matched patents with allergic rhinitis . The AS skin test and intradermal histamine-induced wheal and flare reaction were performed at baseline ( without AH ) , after 8 and 16 weeks ( under AH treatment ) . Forty-six subjects were included in the CIU group , 21 were in the R-CIU group , and 44 were in the control group . Under AH therapy , the skin reaction to intradermal histamine injection was significantly diminished in all study groups . In the R-CIU group , fexofenadine at 180 mg did not suppress AS-induced wheal reaction ( 5.96 ± 2.25 mm ; p = 0.85 ) , and with a fourfold AH dose some reduction of AS-induced wheal ( 3.79 ± 1.74 mm ; p = 0.008 ) was observed but remained larger than in the CIU ( 2.31 ± 1.12 ; p = 0.006 ) and control groups ( 2.52 ± 1.36 ; p = 0.037 ) . AHs do not inhibit the wheal induced by the intradermal injection of AS in R-CIU .

Antihistamines

antihistamines ( AHs )

autologous serum ( AS )

histamine

fexofenadine

fexofenadine

fexofenadine

histamine-induced

fexofenadine

skin wheal and flare reaction

AS-induced wheal reaction


Heat-exercise performance of pyridostigmine-treated subjects wearing chemical protective clothing . Pyridostigmine bromide is currently the pretreatment of choice for operation in a chemical warfare ( CW ) environment . Under CW conditions , subjects are exposed to thermal stress caused by CW protective clothing . This investigation was conducted to determine if pyridostigmine affects various physiological and biophysical parameters of human temperature regulation in subjects wearing CW protective clothing . Pyridostigmine was administered orally in a randomized double-blind cross-over study in four doses of 30 mg every 8 h. An average of 33 % whole blood cholinesterase inhibition was induced in the pyridostigmine treated group 4 h after ingestion of last tablet . The subjects were exposed to 170 min exercise-heat stress ( Tdb = 33 degrees C ; rh = 60 % ) consisting of 60 min in a sitting position and two 50-min walks ( 1.39 m.s-1 , 5 % grade ) separated by 10 min of rest . Non-evaporative heat exchange was significantly higher , -14.0 and -10.6 W.m-2 ( p less than 0.03 ) , for the pyridostigmine-treated subjects . No additional differences were found between treatments in the physiological responses and heat balance parameters at the end of exposure : heart rate ( HR ) was ( mean +/- S.D . ) 154 +/- 16 and 151 +/- 24 bpm , rectal temperature ( Tre ) was 39.0 +/- 0.4 and 38.9 +/- 0.2 degrees C , heat storage over the 2 h of exercise was 62 +/- 15 and 70 +/- 15 W.m-2 , and sweat rate was 832 +/- 185 and 748 +/- 52 g.h-1 , in the pyridostigmine and placebo treatments , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS )

pyridostigmine-treated

Pyridostigmine bromide

pyridostigmine

Pyridostigmine

pyridostigmine

pyridostigmine-treated

Non-evaporative heat exchange

thermal stress


Disparities in transition planning for youth with autism spectrum disorder . OBJECTIVE Little is known about accessibility to health care transition ( HCT ) services for youth with autism spectrum disorder ( ASD ) . This study expands our understanding by examining the receipt of HCT services in youth with ASD compared with youth with other special health care needs ( OSHCN ) . METHODS We used the 2005-2006 National Survey of Children with Special Health Care Needs to examine receipt of HCT services for youth ( aged 12-17 years ) with ASD and youth with OSHCN . Logistic regression analyses explored whether individual , family , or health system factors were associated with receipt of HCT services for youth with ASD . RESULTS Whereas half of youth with OSHCN received HCT services , less than a quarter of youth with ASD did . Only 14 % of youth with ASD had a discussion with their pediatrician about transitioning to an adult provider , less than a quarter had a discussion about health insurance retention , and just under half discussed adult health care needs or were encouraged to take on appropriate responsibility . Logistic regression analyses indicated that having a developmental disability or multiple health conditions in addition to ASD and quality of health care were strong predictors of HCT , whereas demographic and family variables accounted for little variance . CONCLUSIONS Youth with ASD experience disparities in access to HCT services . Youth with comorbid conditions are at greatest risk for poor access to HCT services and increased quality of care has a positive effect . Research is needed to understand barriers to care and develop policy and practice guidelines tailored for youth with ASD .

transition planning

health care transition ( HCT )

HCT services

HCT

HCT

HCT services

health insurance retention

HCT

youth

autism spectrum disorder

youth

autism spectrum disorder ( ASD )

youth

ASD

youth

We used the 2005-2006 National Survey

youth ( aged 12-17 years )

ASD

OSHCN

Youth

ASD

comorbid conditions

youth

ASD


Sex risk behavior among adolescent and young adult children of opiate addicts : outcomes from the focus on families prevention trial and an examination of childhood and concurrent predictors of sex risk behavior . This study reports on rates and predictors of sex risk behavior among a sample of adolescent and young adult children of parents enrolled in methadone treatment for opiate addiction . Data are from 151 participants ( 80 males , 71 females ) in the Focus on Families ( FOF ) project , a randomized trial of a family intervention and a study of the development of at-risk children . The study participants are children of parents enrolled in methadone treatment between 1990 and 1993 . Participants were interviewed in 2005 when they ranged in age from 15 to 29 years . In the year prior to the follow-up , 79 % of the males and 83 % of females were sexually active , 26 % of males and 10 % of females had more than one partner in the prior year , and 34 % of males and 24 % of females reported having sex outside of a committed relationship . Twenty-four percent of males and 17 % of females met criteria for high-risk sexual behavior , reporting casual or multiple partners in the prior year and inconsistent condom use . Participants in the intervention and control conditions did not differ significantly in terms of any measure of sex risk behavior examined . None of the measures of parent behavior and family processes derived from data at baseline of the FOF study predicted whether participants engaged in high-risk sex . Among measures derived from data collected at long-term follow-up , however , having ever met criteria for substance abuse or dependence predicted greater likelihood of high-risk sexual behavior , and being married or being in a romantic relationship was associated with lower likelihood of high-risk sexual behavior . The findings point to the important role of committed relationships in regulating sex risk behavior among this population , as well as heightened levels of sex risk behavior associated with substance abuse or dependence .

methadone

family intervention

methadone treatment

intervention

control

Sex risk behavior

high-risk sexual behavior

sex risk behavior

high-risk sex .

high-risk sexual behavior

high-risk sexual behavior .

sex risk behavior

sex risk behavior

adolescent and young adult children

opiate addicts

adolescent and young adult children

males , 71 females

at-risk children

15 to 29 years


Is altered central pain processing related to disease stage in chronic pancreatitis patients with pain ? An exploratory study . BACKGROUND The most dominant feature in chronic pancreatitis is intense abdominal pain . Changes in spinal and/or supraspinal central nervous system pain processing due to visceral nociceptive input play an important role in this pain . How altered pain processing is related to disease stage still needs study . METHODOLOGY/PRINCIPAL FINDINGS Sixty chronic pancreatitis patients were compared to 15 healthy controls . Two subgroups of pancreatitis patients were defined based on the M-ANNHEIM severity index of chronic pancreatitis ; i.e . moderate and severe . Pain detection and tolerance thresholds for pressure and electric stimuli were measured in six selected dermatomes ( C5 , T4 , T10 , L1 , L4 and T10BACK ) . In addition , the conditioned pain modulation response to cold pressor task was determined . These measures were compared between the healthy controls and chronic pancreatitis patients . Severe pancreatitis patients showed lower pain thresholds than moderate pancreatitis patients or healthy volunteers . Healthy controls showed a significantly larger conditioned pain modulation response compared to all chronic pancreatitis patients taken together . CONCLUSIONS/SIGNIFICANCE The present study confirms that chronic pancreatitis patients show signs of altered central processing of nociception compared to healthy controls . The study further suggests that these changes , i.e . central sensitization , may be influenced by disease stage . These findings underline the need to take altered central pain processing into account when managing the pain of chronic pancreatitis .

altered pain processing

pressure and electric stimuli

pain modulation response

cold pressor task

altered central processing

pain thresholds

pain modulation

chronic pancreatitis patients with pain


Association between weight loss and improvement of ventricular systolic function in advanced heart failure . In heart failure ( HF ) , longitudinal changes in ventricular ejection fraction are poorly studied . The authors ' objective was to document the dynamic changes in systolic function of both ventricles during acute HF and after a 3-month follow-up period , and to identify factors associated with ventricular improvement . A limited access dataset from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness ( ESCAPE ) trial provided by The National Heart , Lung , and Blood Institute was analyzed . In patients admitted to the hospital with acute HF , both ventricles were evaluated by echocardiography on admission , at discharge , and at 3 months . From baseline to 3 months , left ventricular ejection fraction ( LVEF ) increased in 43.4 % of patients , decreased in 23.9 % , and remained unchanged in 32.7 % . Similarly , right ventricular systolic function improved in 40.9 % , deteriorated in 25.0 % , and remained stable in 34.1 % . Weight loss during index admission and cardiac index/cardiac output increase were the only factors associated with LVEF improvement from baseline to month 3 . There was no difference between ischemic and nonischemic etiology . In acute HF , ischemic or nonischemic , systolic function of the ventricles improved during 3 months in about 40 % of patients and remained unchanged or deteriorated in the rest . Weight loss and increase in cardiac index/output during hospitalization was associated with improvement in LVEF .

weight loss

Weight loss

Weight loss

weight loss

right ventricular systolic function

Weight loss during index admission

cardiac index/cardiac output

Weight loss

cardiac index/output

LVEF .

advanced heart failure

Heart Failure

acute HF


Rifampicin plus isoniazid for the prevention of tuberculosis in an immigrant population . OBJECTIVES To compare the tolerance , adherence and effectiveness of two approaches for the treatment of latent tuberculosis infection ( LTBI ) : 6 months of isoniazid ( 6H ) vs. 3 months of isoniazid plus rifampicin ( 3RH ) . POPULATION Immigrants with LTBI . METHODS Participants were enrolled in a controlled , randomised clinical trial in Barcelona , Spain , from April 2001 to April 2005 . Monthly follow-up was done to assess tolerance , side effects and adherence . Effectiveness was evaluated at 5 years . RESULTS In the 590 subjects enrolled , the rate of adherence was greater in the 3RH than in the 6H arm ( 72 % vs. 52.4 % , P = 0.001 ) . No differences between study arms were observed with respect to hepatotoxicity or side effects . Variables associated with non-adherence were diagnosis by screening ( OR 1.88 , 95 % CI 1.26-2.82 , P = 0.001 ) , illegal immigration status ( OR 1.48 , 95 % CI 1.01-2.15 , P = 0.03 ) , unemployment ( OR 1.91 , 95 % CI 1.28-2.85 , P = 0.0008 ) , illiteracy ( OR 1.73 , 95 % CI 1.04-2.88 , P = 0.02 ) , lack of family support ( OR 3.7 , 95 % CI 2.54-5.4 , P = 0.001 ) and the 6-month treatment regimen ( OR 2.45 , 95 % CI 1.68-3.57 , P = 0.0001 ) . None of the patients who completed either treatment developed tuberculosis . CONCLUSIONS The 3RH regimen facilitates adherence to LTBI treatment and offers a safe , well-tolerated and effective alternative .

Rifampicin plus isoniazid

isoniazid ( 6H )

isoniazid plus rifampicin ( 3RH )

3RH regimen

rate of adherence

hepatotoxicity or side effects .

screening

illegal immigration status

unemployment

illiteracy

lack of family support

6-month treatment regimen

tuberculosis .

Immigrants with LTBI


Family economic empowerment and mental health among AIDS-affected children living in AIDS-impacted communities : evidence from a randomised evaluation in southwestern Uganda . OBJECTIVE The authors examine whether an innovative family economic empowerment intervention addresses mental health functioning of AIDS-affected children in communities heavily impacted by HIV/AIDS in Uganda . METHODS A cluster randomised controlled trial consisting of two study arms , a treatment condition ( n=179 ) and a control condition ( n=118 ) , was used to examine the impact of the family economic empowerment intervention on children 's levels of hopelessness and depression . The intervention comprised matched children savings accounts , financial management workshops and mentorship . Data were collected at baseline and 12 months post-intervention . RESULTS Using multivariate analysis with several socioeconomic controls , the authors find that children in the treatment condition ( receiving the intervention ) report significant improvement in their mental health functioning . Specifically , the intervention reduces hopelessness and depression levels . On the other hand , children in the control condition ( not receiving the intervention ) report no changes on both measures . CONCLUSIONS The findings indicate that children with poor mental health functioning living in communities affected by HIV/AIDS may benefit from innovative family economic empowerment interventions . As measures of mental health functioning , both hopelessness and depression have long-term negative psychosocial and developmental impacts on children . These findings have implications for public health programmes intended for long-term care and support of children living in resource poor AIDS-impacted communities .

Family economic empowerment

family economic empowerment

control condition

mental health functioning .

hopelessness and depression levels .

hopelessness and depression


Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced , hormone-receptor-positive breast cancer : a randomised , controlled , double-blind , phase 2 trial . BACKGROUND Insulin-like growth factors ( IGF-1 and IGF-2 ) bind to the IGF-1 receptor ( IGF-1R ) , increasing cell proliferation and survival . Ganitumab is a monoclonal IgG1 antibody that blocks IGF-1R . We tested the efficacy and safety of adding ganitumab to endocrine treatment for patients with hormone-receptor-positive breast cancer . METHODS We did this phase 2 trial in outpatient clinics and hospitals . We enrolled postmenopausal women with hormone-receptor-positive , locally advanced or metastatic breast cancer previously treated with endocrine treatment . They were randomly assigned ( 2:1 ) with a central randomisation schedule to receive intravenous ganitumab 12 mg per kg bodyweight or placebo in combination with open-label intramuscular fulvestrant ( 500 mg on day 1 , then 250 mg on days 15 , 29 , and every 28 days ) or oral exemestane ( 25 mg once daily ) on a 28-day cycle . Patients , investigators , study monitors , and the sponsor staff were masked to treatment allocation . Response was assessed every 8 weeks . The primary endpoint was median progression-free survival in the intention-to-treat population . We analysed overall survival as one of our secondary endpoints . The study is registered at ClinicalTrials.gov , number NCT00626106 . FINDINGS We screened 189 patients and enrolled 156 ( 106 in the ganitumab group and 50 in the placebo group ) . Median progression-free survival did not differ significantly between the ganitumab and placebo groups ( 3·9 months , 80 % CI 3·6-5·3 vs 5·7 months , 4·4-7·4 ; hazard ratio [ HR ] 1·17 , 80 % CI 0·91-1·50 ; p=0·44 ) . However , overall survival was worse in the the ganitumab group than in the placebo group ( HR 1·78 , 80 % CI 1·27-2·50 ; p=0·025 ) . With the exception of hyperglycaemia , adverse events were generally similar between groups . The most common grade 3 or higher adverse event was neutropenia-reported by six of 106 ( 6 % ) patients in the ganitumab group and one of 49 ( 2 % ) in the placebo group . Hyperglycaemia was reported by 12 of 106 ( 11 % ) patients in the ganitumab group ( with six patients having grade 3 or 4 hyperglycaemia ) and none of 49 in the placebo group . Serious adverse events were reported by 27 of 106 ( 25 % ) patients in the ganitumab group and nine of 49 ( 18 % ) patients in the placebo group . INTERPRETATION Addition of ganitumab to endocrine treatment in women with previously treated hormone-receptor-positive locally advanced or metastatic breast cancer did not improve outcomes . Our results do not support further study of ganitumab in this subgroup of patients . FUNDING Amgen .

Ganitumab

exemestane

fulvestrant

Ganitumab

intravenous ganitumab

placebo

open-label intramuscular fulvestrant

exemestane

ganitumab

ganitumab

cell proliferation

survival

efficacy

safety

median progression-free survival

overall survival

Median progression-free survival


Safety , pharmacokinetics and pharmacodynamics of GS-9620 , an oral Toll-like receptor 7 agonist . BACKGROUND GS-9620 is a novel oral agonist of Toll-like receptor 7 ( TLR7 ) in development for the treatment of chronic viral hepatitis . TLR7 is a highly conserved innate immune receptor expressed primarily on plasmacytoid dendritic cells and B lymphocytes . The aim of this double-blind , placebo-controlled , single ascending-dose study was to investigate the safety , tolerability , pharmacokinetics and pharmacodynamics of GS-9620 in healthy volunteers . METHODS In total , 75 healthy volunteers ( 8 subjects in each of the 10 cohorts ; 5 subjects participated in two cohorts ) were randomized ( 6:2 ) to receive a single dose of GS-9620 ( 0.3 , 1 , 2 , 4 , 6 , 8 or 12 mg ) or placebo . RESULTS GS-9620 was well-absorbed and well-tolerated in oral doses up to 12 mg . Minimal treatment-related adverse events were seen at doses up to 8 mg. Serum interferon ( IFN ) -α was only detected in subjects who received 8 or 12 mg doses , and the adverse event profile at 8 and 12 mg doses was generally consistent with that associated with IFN-α exposure ( flu-like symptoms ) , consistent with the mechanism of TLR7 agonism . All adverse events resolved within 72 h. Induction of chemokines/cytokines and IFN-stimulated genes were seen at GS-9620 doses ≥ 2 mg , well below doses that induced serum IFN-α or led to clinical adverse events . CONCLUSIONS GS-9620 demonstrates safety and pharmacodynamic activity at doses up to 12 mg. Pharmacodynamic activity is seen before adverse events , suggesting the potential for induction of an antiviral response without systemic adverse events in subjects with chronic viral hepatitis .

placebo-controlled

safety

tolerability

pharmacokinetics

pharmacodynamics

well-absorbed

well-tolerated

healthy volunteers .


Low body mass index and dyslipidemia in dialysis patients linked to elevated plasma fibroblast growth factor 23 . BACKGROUND Fibroblast growth factor 23 ( FGF23 ) has been associated with death in dialysis patients . Since FGF23 shares structural features with FGF19 subfamily members that exert hormonal control of fat mass , we hypothesized that high circulating FGF23 concentrations would be associated with the development of a uremic lipid profile and lower body mass index ( BMI ) . METHODS This study was conducted among 654 patients receiving chronic hemodialysis . C-terminal FGF23 concentrations were measured in stored plasma samples . Linear regression was used to examine the cross-sectional associations of plasma FGF23 concentrations with BMI , total cholesterol ( TC ) , low-density lipoprotein-cholesterol ( LDL-C ) , high-density lipoprotein-cholesterol ( HDL-C ) and triglycerides . Cox proportional hazard models were used to examine the association between FGF23 concentrations and all-cause mortality . RESULTS Participants had a mean age of 60 ± 11 years and a median ( IQR ) FGF23 concentration of 4,212 ( 1,411-13,816 ) RU/ml . An increase per SD in log10 FGF23 was associated with lower BMI ( β = -1.11 ; p = 0.008 ) , TC ( β = -6.46 ; p = 0.02 ) , LDL-C ( β = -4.73 ; p = 0.04 ) and HDL-C ( β = -2.14 ; p = 0.03 ) ; after adjusting for age , gender , race , cardiovascular risk factors , serum albumin , markers of mineral metabolism , and use of lipid-lowering drugs . The association of FGF23 with death was attenuated after adjustment for HDL-C ( HR of highest quartile 1.53 , 95 % CI 1.06-2.20 compared to lowest quartile ) . CONCLUSION These results indicate that higher plasma FGF23 levels are associated with lower BMI and dyslipidemia in dialysis patients . The association between FGF23 and death may be mediated through unexplored metabolic risk factors unrelated to mineral metabolism .

dialysis

dialysis

hemodialysis

C-terminal FGF23 concentrations


Intervention for ineffective airway clearance in asthmatic children : a controlled and randomized clinical trial . This study aimed to analyse the effectiveness of an intervention for the nursing diagnosis of ineffective airway clearance in asthmatic children . A blinded , randomized and controlled clinical trial was developed in a paediatric hospital located on northeast of Brazil with 42 asthmatic children aged ≤ 36 months . The children were randomly divided into two groups ( intervention and control ) by means of a simple drawing . The applied intervention included actions related to change of positioning and stimulation of cough . The main findings of this study show that before the intervention , no significant difference was observed in the health status of the children . After the intervention , the indicators of choking ( 16.83 vs. 26.17 , P = 0.007 ) and adventitious breath sounds ( 16.4 vs. 26.6 , P = 0.005 ) were higher , on average , in the intervention group . It was observed an improvement in obstructive symptoms in children who received the intervention proposed .

ineffective airway clearance

ineffective airway clearance


Modulation of the intestinal environment , innate immune response , and barrier function by dietary threonine and purified fiber during a coccidiosis challenge in broiler chicks . Coccidiosis is a major contributor to economic losses in the poultry industry due to its detrimental effects on growth performance and nutrient utilization . We hypothesized that the combined effects of supplemental dietary Thr and purified fiber may modulate the intestinal environment and positively affect intestinal immune responses and barrier function in broiler chicks infected with Eimeria maxima . A Thr-deficient basal diet ( 3.1 g of Thr/kg of diet ) was supplemented with 70 g/kg of silica sand ( control ) or high-methoxy pectin and 1 of 2 concentrations of Thr ( 1.8 or 5.3 g/kg of diet ; 4 diets total ) , and fed to chicks from hatch to d 16 posthatch . On d 10 posthatch , chicks received 0.5 mL of distilled water or an acute dose of Eimeria maxima ( 1.5 × 10 ( 3 ) sporulated oocytes ) with 6 replicate pens of 6 chicks per each of 8 treatment combinations ( 4 diets and 2 inoculation states ) . Body weight gain , feed intake , and G : F increased ( P < 0.01 ) with addition of 5.3 g of Thr/kg of diet . Eimeria maxima schizonts were present only in intestinal tissue sampled from infected birds ( P < 0.01 ) . Weights of cecal digesta were highest ( P < 0.01 ) in pectin-fed birds , and ceca with the heaviest weights also had the highest concentrations of total short-chain fatty acids . Expression of interleukin-12 in ileal mucosa was highest ( P < 0.01 ) in infected birds receiving the control diet with 5.3 g of supplemental Thr/kg . In cecal tonsils , interferon-γ expression was highest in infected birds receiving the control diet ( fiber × infection , P < 0.05 ) ; interferon-γ expression was lowest in infected birds fed the high Thr diet ( Thr × infection , P < 0.05 ) . There were no differences due to infection or Thr supplementation for cytokine expression in birds fed pectin-containing treatments . Overall , we conclude that although pectin has some protective function against coccidiosis , Thr supplementation had the greatest effect on intestinal immune response and maintenance of near normal growth in young broiler chicks infected with E. maxima .

dietary threonine

purified fiber

supplemental dietary Thr

purified fiber

Thr-deficient basal

70 g/kg of silica sand ( control )

0.5 mL of distilled water

acute dose of Eimeria maxima

broiler chicks

poultry

Eimeria maxima


A randomized controlled trial of COMPASS web-based and face-to-face teacher coaching in autism . OBJECTIVE Most children with autism rely on schools as their primary source of intervention , yet research has suggested that teachers rarely use evidence-based practices . To address the need for improved educational outcomes , a previously tested consultation intervention called the Collaborative Model for Promoting Competence and Success ( COMPASS ; Ruble , Dalrymple , & McGrew , 2010 ; Ruble , Dalrymple , & McGrew , 2012 ) was evaluated in a 2nd randomized controlled trial , with the addition of a web-based group . METHOD Forty-nine teacher-child dyads were randomized into 1 of 3 groups : ( 1 ) a placebo control ( PBO ) group , ( 2 ) COMPASS followed by face-to-face ( FF ) coaching sessions , and ( 3 ) COMPASS followed by web-based ( WEB ) coaching sessions . Three individualized goals ( social , communication , and independence skills ) were selected for intervention for each child . The primary outcome of independent ratings of child goal attainment and several process measures ( e.g. , consultant and teacher fidelity ) were evaluated . RESULTS Using an intent-to-treat approach , findings replicated earlier results with a very large effect size ( d = 1.41 ) for the FF group and a large effect size ( d = 1.12 ) for the WEB group relative to the PBO group . There were no differences in overall change across goal domains between the FF and WEB groups , suggesting the efficacy of videoconferencing technology . CONCLUSIONS COMPASS is effective and results in improved educational outcomes for young children with autism . Videoconferencing technology , as a scalable tool , has promise for facilitating access to autism specialists and bridging the research-to-practice gap .

COMPASS web-based

face-to-face teacher coaching

a placebo control ( PBO ) group

COMPASS

autism

children

autism

Forty-nine

child

children

autism


Comparative in vitro dissolution and in vivo bioavailability of diflunisal/naproxen fixed-dose combination tablets and concomitant administration of diflunisal and naproxen in healthy adult subjects . A simple validated high-performance liquid chromatography ( HPLC ) assay was developed for determination of diflunisal and naproxen in human plasma samples . This is to compare the bioavailability of diflunisal-naproxen fixed-dose combination ( FDC ) with their separate dosage forms . The in vitro dissolution study was adopted to compare the dissolution behavior of FDC with respect to separate marketed tablets . In vivo study was conducted according to a single-center , randomized , single-dose , laboratory-blinded , 2 Way , Cross-Over Study with a washout period of 10 days . Under fasting conditions , 24 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either one FDC tablet or co-administration of two separate diflunisal and naproxen marketed tablets . Plasma samples were obtained over a 72-h interval and analyzed for diflunisal and naproxen by reversed phase liquid chromatography with UV detection . The pharmacokinetic parameters Cmax , AUC0-t , AUC0-∞ , tmax , and t1/2 were determined from plasma concentration-time profiles . The 90 % confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUCt-∞ of the 2 treatments were within the acceptable range ( 0.8-1.25 ) for bioequivalence . From pharmacokinetic and in vitro studies perspectives , 1 FDC tablet demonstrated similar relative bioavailability with the 2 individual -reference tablets .

dissolution behavior of FDC

diflunisal and naproxen


Developing the Ho'ouna Pono substance use prevention curriculum : collaborating with Hawaiian youth and communities . This article briefly outlines a collaboration among communities on Hawai'i Island and a university-based research team to develop , implement , and evaluate a school-based substance use prevention curriculum called Ho'ouna Pono . In addition to providing a rationale for the project , the goal of this paper is fourfold . First , an overview of the Ho'ouna Pono research results to date ( 2007-2013 ) is provided . Second , within this overview , the ways in which selected results informed program development are highlighted . Third , the curriculum is briefly described , and finally , the role of the students and community in the video production is described .

Ho'ouna Pono

Hawaiian youth and communities .


Association between frequency of ready-to-eat cereal consumption , nutrient intakes , and body mass index in fourth- to sixth-grade low-income minority children . BACKGROUND The consumption of non-ready-to-eat cereal and ready-to-eat cereal ( RTEC ) breakfasts have been associated with increased nutrient intakes and lower body mass index ( BMI ) . These relationships have not been examined in low-income minority children . OBJECTIVES To evaluate , in low-income minority children , whether there is a relationship among the frequency of RTEC consumption and nutrient intakes measured at baseline , and whether there is a relationship between the frequency of RTEC and BMI controlling for age , sex , ethnicity , and energy intake . DESIGN A longitudinal study design where a cohort was followed for 3 years . SUBJECTS/SETTING Participants were 625 fourth- through sixth-grade , low-income children living in San Antonio , Texas , and enrolled in the control arm of the Bienestar Diabetes Prevention Program 's cluster randomized trial . Three multiple-pass 24-hour dietary recalls were collected at the beginning of their fourth-grade year and at the end of their fifth- and sixth-grade years . Children 's age , sex , ethnicity , and height and weight ( used to calculate BMI ) were collected between August 2001 and May 2004 . STATISTICAL ANALYSES PERFORMED Descriptive and inferential statistical analyses were performed . The frequency of breakfast consumption was examined using a 6×4 cross-tabulation table with χ ( 2 ) test to establish categorical differences . The degree of association between BMI percentile and frequency of RTEC consumption adjusted for age , sex , ethnicity , and nutrition-related parameters were calculated using a partial correlation multivariate linear model analysis . RESULTS There was a significant positive relationship between the frequency of RTEC consumption and nutrient intakes measured at baseline . There was also a significant inverse relationship between frequency of RTEC consumption and BMI percentile over the cumulative 3-year period controlling for age , sex , ethnicity , and energy intake . CONCLUSIONS Children who frequently consumed RTEC had greater intakes of essential nutrients at baseline and significantly lower BMI over a 3-year period .

ready-to-eat cereal ( RTEC )

RTEC

RTEC

body mass index

BMI

frequency of RTEC consumption

nutrient intakes

of essential nutrients

low-income minority

children

children

Children 's age

CONCLUSIONS Children


Topical treatment of tinea pedis using 6 % coriander oil in unguentum leniens : a randomized , controlled , comparative pilot study . BACKGROUND The antifungal activity of coriander oil has already been demonstrated in vitro . OBJECTIVE Evaluation of the efficacy and tolerability of 6 % coriander oil in unguentum leniens in the treatment of interdigital tinea pedis . METHODS Half-side comparative pilot study on subjects with symmetric , bilateral interdigital tinea pedis . Active drug and placebo control were applied twice daily on the affected areas , and follow-up visits were performed on days 14 and 28 . RESULTS 40 participants ( mean age 52.5 years , 60 % male ) were included in the study . For 6 % coriander oil in unguentum leniens , a highly significant improvement of the clinical signs ( p < 0.0001 ) was observed during the entire observation period ; the number of positive fungal cultures also tended to decrease ( p = 0.0654 ) . The tolerability of the tested substances was good . CONCLUSION Coriander oil is effective and well tolerated in the treatment of interdigital tinea pedis .

coriander oil

coriander oil

6 % coriander oil

placebo

Coriander oil

efficacy

tolerability

clinical signs

number of positive fungal cultures

tolerability


Neurophysiological responses to faces and gaze direction differentiate children with ASD , ADHD and ASD+ADHD . Children with autism spectrum disorder ( ASD ) and attention deficit hyperactivity disorder ( ADHD ) demonstrate face processing abnormalities that may underlie social impairment . Despite substantial overlap between ASD and ADHD , ERP markers of face and gaze processing have not been directly compared across pure and comorbid cases . Children with ASD ( n=19 ) , ADHD ( n=18 ) , comorbid ASD+ADHD ( n=29 ) and typically developing ( TD ) controls ( n=26 ) were presented with upright/inverted faces with direct/averted gaze , with concurrent recording of the P1 and N170 components . While the N170 was predominant in the right hemisphere in TD and ADHD , children with ASD ( ASD/ASD+ADHD ) showed a bilateral distribution . In addition , children with ASD demonstrated altered response to gaze direction on P1 latency and no sensitivity to gaze direction on midline-N170 amplitude compared to TD and ADHD . In contrast , children with ADHD ( ADHD/ASD+ADHD ) exhibited a reduced face inversion effect on P1 latency compared to TD and ASD . These findings suggest children with ASD have specific abnormalities in gaze processing and altered neural specialisation , whereas children with ADHD show abnormalities at early visual attention stages . Children with ASD+ADHD are an additive co-occurrence with deficits of both disorders . Elucidating the neural basis of the overlap between ASD and ADHD is likely to inform aetiological investigation and clinical assessment .

face processing abnormalities

ERP markers of face and gaze processing

response to gaze direction

sensitivity to gaze direction

face inversion effect

abnormalities

children with ASD


[ Effects of dujieqing oral liquid on the promoter methylation of the MGMT gene in middle-and-late stage tumor patients receiving chemotherapy ] . OBJECTIVE To observe the effects of Dujieqing Oral Liquid ( DJQ ) on the promoter methylation of the O6-methylguanine-DNA methyltransferase ( MGMT ) gene in the plasma DNA samples from middle-and-late stage tumor patients receiving chemotherapy . METHODS Recruited 60 patients were randomly assigned to the treatment group ( treated by conventional chemotherapy combined DJQ , 20 mL each time , three times daily ) and the control group ( treated by chemotherapy alone ) , 30 in each group . The therapeutic course was 8 weeks . The promoter methylation of the MGMT gene in the plasma DNA samples form middle-and-late stage tumor patients receiving chemotherapy was detected before and after treatment using nested methylation-specific polymerase chain reaction ( MSP ) . Meanwhile , the peripheral hemogram was detected . The clinical efficacy and toxic/adverse reactions were assessed using Karnofsky performance scale ( KPS ) . RESULTS Results of the promoter methylation of MGMT genes showed that methylation rate was 20.00 % in the treatment group and 46.67 % in the control group ( P < 0.05 ) . Compared with before treatment , the KPS was significantly improved in the treatment group after treatment , while it significantly decreased in the control group after treatment ( both P < 0.05 ) . There was statistical difference in the KPS between the two groups after treatment ( P < 0.01 ) . The toxic/adverse reactions were milder in the treatment group than in the control group ( P < 0.01 ) . CONCLUSIONS DJQ showed efficiency synergism and toxicity reducing effects , but with no effect on the hematopoietic function of the bone marrow . MGMT gene was indicated as DJQ 's target point for efficiency synergism and toxicity reducing . The efficiency synergism and toxicity reducing effects were achieved by regulating the activities of MGMT gene .

dujieqing oral liquid

Dujieqing Oral Liquid ( DJQ )

conventional chemotherapy combined DJQ

DJQ

DJQ 's

clinical efficacy

toxic/adverse reactions

KPS

KPS

toxic/adverse reactions

middle-and-late stage tumor

receiving chemotherapy

middle-and-late stage tumor

middle-and-late stage tumor


Parenting stress in the infant aphakia treatment study . OBJECTIVE To evaluate parenting stress following infants ' cataract extraction surgery , and to determine if levels of stress differ between 2 treatments for unilateral congenital cataract in a randomized clinical trial . METHODS At surgery , an intraocular lens ( IOL ) was implanted or children were left aphakic , treated with contact lens ( CL ) . Stress measures were administered 3 months after surgery and at the first visit after the visual acuity ( VA ) assessment done at 12 months of age . RESULTS Caregivers in the IOL group reported higher levels of stress than those in the CL group 3 months after surgery , but there were no group differences in stress scores at the post-VA assessment . Stress scores did not change differentially for participants assigned to IOL versus CL treatments . CONCLUSIONS Treatment assignment did not have a significant impact on caregiver stress during infancy or on the change in stress during the child 's first 2 years of life .

cataract extraction surgery

intraocular lens ( IOL ) was implanted

IOL

CL

IOL

CL

Parenting stress

unilateral congenital

stress

stress scores

Stress scores

caregiver stress

Parenting stress

parenting stress

infants

infancy


The addition of amifostine to carboplatin and paclitaxel based chemoradiation in locally advanced non-small cell lung cancer : long-term follow-up of Radiation Therapy Oncology Group ( RTOG ) randomized trial 9801 . INTRODUCTION We report the long-term results of RTOG 9801 , a randomized trial investigating the ability of amifostine , a radioprotector , to reduce chemoradiation-induced esophagitis . METHODS Patients with stages II and IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m2 intravenously ( IV ) and carboplatin area under the curve ( AUC ) 6 both days 1 and 22 , followed by concurrent weekly paclitaxel ( 50 mg/m2 ) and carboplatin ( AUC 2 ) , with hyperfractionated radiation therapy ( 69.6 Gy at 1.2 Gy BID ) . Patients were randomly assigned to amifostine ( AM ) 500 mg IV four times per week or no-AM during chemoradiotherapy . Stratification factors included age ( < 70 vs. ≥70 years ) , stage and performance status . RESULTS 243 patients ( pts ) were enrolled ; 120 received AM , 123 received no-AM . Two pts on each arm were found ineligible . Overall , 85 % of patients were ≤70 years ; 75 % had a KPS ≥90 . 34 % had squamous histology . With median follow-up of 96.3 months ( for patients still alive ) , overall survival was identical ( hazard ratio 1.03 ( 0.79-1.34 ) , NS ) : five-year survival 17 % in both arms . The incidence of late grade 3-5 toxicities was 16 % in the AM arm and 19 % in the control arm ( hazard ratio 1.24 ( 0.66-2.32 ) , NS ) . There was no significant difference between the arms regarding overall survival , disease-free survival or long-term toxicity . CONCLUSION The chemoradiation regimen of carboplatin and paclitaxel produced long-term results in the multi-institutional setting comparable to other regimens . Amifostine did not appear to compromise survival . As done in RTOG 9801 , more consistent reporting of long term toxicity is needed for comparison of different chemoradiation regimens .

amifostine

carboplatin

paclitaxel

chemoradiation

amifostine

paclitaxel

carboplatin

paclitaxel

carboplatin

hyperfractionated radiation therapy

amifostine

overall survival

five-year survival

incidence of late grade 3-5 toxicities

disease-free survival

long term toxicity


Development of the Therapist Empathy Scale . BACKGROUND Few measures exist to examine therapist empathy as it occurs in session . AIMS A 9-item observer rating scale , called the Therapist Empathy Scale ( TES ) , was developed based on Watson 's ( 1999 ) work to assess affective , cognitive , attitudinal , and attunement aspects of therapist empathy . The aim of this study was to evaluate the inter-rater reliability , internal consistency , and construct and criterion validity of the TES . METHOD Raters evaluated therapist empathy in 315 client sessions conducted by 91 therapists , using data from a multi-site therapist training trial ( Martino et al. , 2010 ) in Motivational Interviewing ( MI ) . RESULTS Inter-rater reliability ( ICC = .87 to .91 ) and internal consistency ( Cronbach 's alpha = .94 ) were high . Confirmatory factor analyses indicated some support for single-factor fit . Convergent validity was supported by correlations between TES scores and MI fundamental adherence ( r range .50 to .67 ) and competence scores ( r range .56 to .69 ) . Discriminant validity was indicated by negative or nonsignificant correlations between TES and MI-inconsistent behavior ( r range .05 to -.33 ) . CONCLUSIONS The TES demonstrates excellent inter-rater reliability and internal consistency . RESULTS indicate some support for a single-factor solution and convergent and discriminant validity . Future studies should examine the use of the TES to evaluate therapist empathy in different psychotherapy approaches and to determine the impact of therapist empathy on client outcome .

Therapist Empathy Scale

client sessions

Motivational Interviewing ( MI )

Inter-rater reliability

internal consistency

factor analyses

Convergent validity

TES scores and MI fundamental adherence

competence scores

Discriminant validity

therapist

therapists

Motivational Interviewing

therapist


Effects of low and high protein : carbohydrate ratios in the diet of pregnant gilts on maternal cortisol concentrations and the adrenocortical and sympathoadrenal reactivity in their offspring . Inadequate maternal nutrition during gestation may cause an adverse environment for the fetus leading to alterations of the hypothalamic-pituitary-adrenal ( HPA ) and sympatho-adrenomedullary ( SAM ) systems later in life . In the present study , we investigated the effects of diets with low and high protein : carbohydrate ratios on cortisol concentrations of pregnant gilts as well as the long-term effects on the function of the HPA and SAM axes in their offspring . Throughout gestation , 33 German Landrace gilts were fed high ( HP , 30 % ) , low ( LP , 6.5 % ) , or adequate ( AP , 12.1 % ) protein diets , which were made isocaloric by adjusting the carbohydrate content . The salivary cortisol concentrations of the sows were measured in the course of the gestation period . The offspring were cross-fostered , and the plasma cortisol and catecholamine concentrations of the offspring were determined on postnatal d ( PND ) 1 and 27 and under specific challenging conditions : after weaning ( PND 29 ) and after ACTH and insulin challenges ( PND 68 and 70 , respectively ) . Glucocorticoid receptor ( GR ) binding and neurotransmitter concentrations were measured in stress-related brain regions , and histological analyses of the adrenal were performed . Maternal salivary cortisol concentrations increased throughout gestation ( P < 0.001 ) and the LP gilts had greater salivary cortisol compared with the AP and HP gilts ( P < 0.05 ) . No differences between diets were found for cortisol , corticosteroid-binding globulin , and catecholamine concentrations in plasma and for GR binding in hippocampus and hypothalamus in piglets at PND 1 and 27 . However , the cortisol response to weaning was increased in LP piglets ( P < 0.05 ) , and in HP offspring the basal plasma noradrenaline concentrations were increased ( P < 0.05 ) . The cortisol response to the ACTH and the insulin challenge did not differ between diets . On PND 81 , an increased adrenal medulla area was observed in LP offspring compared with the AP offspring ( P < 0.05 ) . Our results show that maternal diets with aberrant protein : carbohydrate ratios during gestation have moderate long-term effects on the function of the HPA and SAM system in the offspring , which indicates that pigs show a considerable plasticity to cope with maternal malnutrition .

maternal diets with aberrant protein

carbohydrate ratios during gestation

protein : carbohydrate ratios

maternal cortisol concentrations

cortisol concentrations

HPA and SAM axes

salivary cortisol

cortisol response to weaning

adrenal medulla area

aberrant protein : carbohydrate ratios

function of the HPA and SAM system

33 German Landrace gilts


Satisfactory sampling in cytological cervical diagnosis : comparison between a conventional and a new sampling device . AIM Inadequate cervical sampling is the most frequent cause of misdiagnosis in cervical cancer screening . The aim of this study was to test the ability of PapCone® versus the conventional sampling method ( Ayre 's spatula plus cytobrush ) to collect ectocervical and glandular cells . MATERIALS AND METHODS In 18 healthy women , two ecto-endocervical samples , obtained by two different methods , were obtained at a three-month interval . Qualitative and quantitative parameters were evaluated . Ultrastructure features of sampling devices were analyzed by scanning electron microscopy ( SEM ) before and after sampling . RESULTS The χ ( 2 ) test revealed a statistically significant difference between the two methods : PapCone® caused less cell overlap and sampled less white blood cells ( p < 0.05 ) and more metaplastic cells ( p < 0.01 ) . SEM evaluation highlighted the porous and spongy structure of PapCone® that was responsible for the large number of glandular cells on its surface . CONCLUSION Cervical smears performed by PapCone® were adequate and generally easier to screen than conventionally performed ones .

sampling device

cytological cervical diagnosis

cervical cancer

healthy

women


Effect of perioperative parecoxib on postoperative pain and local inflammation factors PGE2 and IL-6 for total knee arthroplasty : a randomized , double-blind , placebo-controlled study . To assess the efficacy of postoperative pain management and the concentration change of PGE-2 and IL-6 of joint fluid with parecoxib after postoperative total knee arthroplasty . In the study , 100 patients experiencing primary TKA were randomly divided into study group , receiving parecoxib sodium ( 40 mg ) intravenously ( IV ) at the completion of surgery and once every 12 h for totally 6 times postoperatively , and placebo group , receiving normal saline 2 mL IV at the same time points . Efficacy was assessed by total amount of morphine consumed , pain intensity , range of motion ( ROM ) , the concentration change of PGE-2 and IL-6 of joint fluid , and postoperative nausea and vomiting ( PONV ) postoperatively . Patients in study group consumed significantly less morphine , experienced significant less pain scores , and obtained significantly more ROM ( P < 0.01 ) compared with that in placebo group during 3 days postoperatively . The concentration of PGE-2 and IL-6 of joint fluid in study group are significantly lower than that in placebo group ( P < 0.01 ) during 24 h postoperatively . The overall incidence of PONV was low and was not significantly different between the two groups . The present study demonstrated that the perioperative administration of parecoxib after primary TKA resulted in significantly improved postoperative analgesic management as defined by reduction in opioid requirement , lower pain scores and ROM , and significantly lowered local inflammation factors PGE2 and IL-6 .

parecoxib

placebo-controlled

parecoxib

parecoxib sodium

efficacy

primary TKA


Efficacy of bepotastine besilate ophthalmic solution 1.5 % for seasonal allergic conjunctivitis : a randomized , placebo-controlled , natural exposure , clinical trial . Allergic conjunctivitis ( AC ) affects an estimated 20 % of the population in the Western world , with a large fraction suffering due to seasonal or perennial allergen exposures . Bepotastine besilate ophthalmic solution ( BBOS ) 1.5 % , a dual-acting histamine ( H ( 1 ) ) receptor antagonist and mast cell stabilizer , is indicated for itching associated with AC . This study was designed to evaluate the efficacy and safety of BBOS 1.5 % for reducing ocular itching associated with AC in subjects enrolled in a natural exposure trial . Eligible subjects in a multicenter , double-masked , randomized , parallel-group , placebo-controlled , natural exposure clinical trial were randomly assigned to either BBOS 1.5 % or placebo eyedrops on a 1:1 basis and instilled 1 drop of the test agent into both eyes twice daily for 2 weeks . The mean change from baseline in instantaneous and reflective ocular itching scores at the end of 2 weeks of treatment were evaluated based on subject-assessed severity of instantaneous and reflective itching . Subject-reported adverse events ( AEs ) were also recorded for safety . Treatment with BBOS 1.5 % significantly reduced instantaneous and reflective ocular itching scores from baseline compared with placebo over the 2-week study period ( p = 0.007 and p = 0.005 , respectively ) . BBOS 1.5 % was well tolerated , and AEs were generally transient and mild . This clinical study indicates BBOS 1.5 % effectively and safely treated ocular itching in a natural exposure allergy study and is a useful treatment option for the management of ocular itching associated with AC . ( ClinicalTrials.gov identifier number : NCT01174823 . )

placebo-controlled

dual-acting histamine

placebo-controlled

BBOS

placebo eyedrops

seasonal allergic conjunctivitis

reflective ocular itching scores

Subject-reported adverse events ( AEs )

tolerated

AEs

effectively

safely

ocular itching

seasonal allergic conjunctivitis

ocular itching

AC

natural exposure trial


JobTIPS : a transition to employment program for individuals with autism spectrum disorders . This study evaluated the effectiveness of an internet accessed training program that included Theory of Mind-based guidance , video models , visual supports , and virtual reality practice sessions in teaching appropriate job interview skills to individuals with high functioning Autism Spectrum Disorders . In a randomized study , twenty-two youth , ages 16-19 , were evaluated during two employment interviews . Half received a training intervention following the initial interview and the half who served as a contrast group did not . Their performance pre and post intervention was assessed by four independent raters using a scale that included evaluation of both Content and Delivery . Results suggest that youth who completed the JobTIPS employment program demonstrated significantly more effective verbal content skills than those who did not .

internet accessed training program

effectiveness

internet accessed training program

Content and Delivery

effective verbal content skills


MEG premotor abnormalities in children with Asperger 's syndrome : determinants of social behavior ? Children with Asperger 's syndrome show deficits in social functioning while their intellectual and language development is intact suggesting a specific dysfunction in mechanisms mediating social cognition . An action observation/execution matching system might be one such mechanism . Recent studies indeed showed that electrophysiological modulation of the " Mu-rhythm " in the 10-12Hz range is weaker when individuals with Asperger 's syndrome observe actions performed by others compared to controls . However , electrophysiological studies typically fall short in revealing the neural generators of this activity . To fill this gap we assessed magnetoencephalographic Mu-modulations in Asperger 's and typically developed children , while observing grasping movements . Mu-power increased at frontal and central sensors during movement observation . This modulation was stronger in typical than in Asperger children . Source localization revealed stronger sources in premotor cortex , the intraparietal lobule ( IPL ) and the mid-occipito-temporal gyrus ( MOTG ) and weaker sources in prefrontal cortex in typical participants compared to Asperger . Activity in premotor regions , IPL and MOTG correlated positively with social competence , whereas prefrontal Mu-sources correlated negatively with social competence . No correlation with intellectual ability was found at any of these sites . These findings localize abnormal Mu-activity in the brain of Asperger children providing evidence which associates motor-system abnormalities with social-function deficits .

observing grasping movements

MEG premotor abnormalities

social behavior

social functioning

social cognition

magnetoencephalographic Mu-modulations

grasping movements

Mu-power

social competence

social competence

intellectual ability

social-function deficits