West vs. West like East vs. West ? A comparison between Italian and US American context sensitivity and Fear of Isolation . Easterners tend to process information more holistically than Westerners . Kim and Markman ( J Exp Soc Psychol 42 ( 3 ) :350-364 , 2006 ) suggest that these differences are rooted in higher chronic levels of Fear of Isolation ( FOI ) for those cultures that process information more holistically . The goal of this study was to determine if these differences and their suggested cause could be found with two different Western cultures . Testing Italian ( IT ) and US American ( US ) adults , we found that IT participants processed information more holistically and had a higher chronic level of FOI than US participants ; furthermore , the manipulation of FOI affected context sensitivity more for IT than for US participants . The results demonstrate that IT participants were more similar to previous research with Eastern populations than with Western populations ( Kim and Markman in J Exp Soc Psychol 42 ( 3 ) :350-364 , 2006 ) and indicate a within-Western culture difference for reasoning styles and support the hypothesis that this difference is due to different chronic levels of FOI .

chronic

differences

FOI affected context sensitivity

different Western cultures

adults

US participants


The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatin-based systemic treatment in advanced colorectal cancer patients . BACKGROUND Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment . Calcium and magnesium ( Ca/Mg ) infusions are frequently used to prevent this toxicity . However , concerns about a negative impact of Ca/Mg infusions on outcome have been raised . We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer ( ACC ) patients treated in the phase III CAIRO2 study . MATERIALS AND METHODS Seven hundred and fifty five previously untreated ACC patients were randomised between treatment with capecitabine , oxaliplatin and bevacizumab or the same combination with the addition of cetuximab . Patients were retrospectively divided into two groups : patients in the Ca/Mg ( + ) group received Ca/Mg at least during their first treatment cycle , and patients in the Ca/Mg ( - ) group did not . RESULTS Seven hundred and thirty two patients were evaluable for this analysis . The Ca/Mg ( + ) group consisted of 551 patients , the Ca/Mg ( - ) group consisted of 181 patients . The incidence of all grade neurotoxicity in the Ca/Mg ( + ) group and the Ca/Mg ( - ) group was 85 % and 92 % , respectively ( p = 0.02 ) , and the incidence of grade ≥ 2 neurotoxicity was 40 % and 45 % , respectively ( p = 0.22 ) . The median PFS in the Ca/Mg ( + ) versus Ca/Mg ( - ) group was 10.1 versus 10.7 months ( p = 0.92 ) , the median OS was 19.8 versus 20.7 months ( p = 0.10 ) , and the response rate was 43.1 % versus 50 % ( p = 0.11 ) , respectively . CONCLUSIONS In this largest retrospective analysis to date we observed that Ca/Mg infusions significantly reduced all grade oxaliplatin-related neurotoxicity . Ca/Mg infusions did not affect the clinical efficacy of treatment .

treatment with

capecitabine

oxaliplatin

and

bevacizumab

Ca/Mg ( + ) group

Ca/Mg

incidence of neurotoxicity

clinical outcome

all grade neurotoxicity

advanced colorectal cancer patients

Seven hundred and fifty five


Endoscopic versus operative gastrostomy : final results of a prospective randomized trial . This study compared operative gastrostomy ( OG ) ( by surgeons ) with endoscopic gastrostomy ( PEG ) ( by physicians ) in a prospective randomized fashion to determine whether one technique was superior . PEG ( Sachs-Vine ) and OG ( Stamm ) were done using local anesthesia . Patients were assessed for complications , mortality , tube function , and cost . Groups were equally matched for indications and underlying disease . Fifty-seven had OG and 64 had attempted PEG . Complications occurred in 26 % of OG patients and 9 % died . Complications occurred in 25 % of PEG patients and 12 % died . Tube feeding was initiated in both groups within a mean of 29 ( 24 to 72 ) hours of the gastrostomy placement . OG cost $ 1675 and PEG $ 979 to perform . Twenty-one PEG patients required endoscopic tube change which raised their total cost to $ 1574 . We conclude there is no difference between OG ( using local anesthesia ) and PEG with regard to morbidity , mortality , or tube function . The endoscopic technique does appear to have economic advantage .

Endoscopic versus operative gastrostomy

operative gastrostomy ( OG )

endoscopic gastrostomy ( PEG )

PEG ( Sachs-Vine )

OG ( Stamm )

PEG

PEG

complications

mortality

tube function

cost

Complications

died

Complications

died

OG cost

endoscopic tube change

raised their total cost

morbidity

mortality

tube function

economic advantage

gastrostomy

operative gastrostomy ( OG )

endoscopic gastrostomy ( PEG )

Fifty-seven

OG

PEG


Trachoma prevalence and associated risk factors in the gambia and Tanzania : baseline results of a cluster randomised controlled trial . BACKGROUND Blinding trachoma , caused by ocular infection with Chlamydia trachomatis , is targeted for global elimination by 2020 . Knowledge of risk factors can help target control interventions . METHODOLOGY/PRINCIPAL FINDINGS As part of a cluster randomised controlled trial , we assessed the baseline prevalence of , and risk factors for , active trachoma and ocular C. trachomatis infection in randomly selected children aged 0-5 years from 48 Gambian and 36 Tanzanian communities . Both children 's eyes were examined according to the World Health Organization ( WHO ) simplified grading system , and an ocular swab was taken from each child 's right eye and processed by Amplicor polymerase chain reaction to test for the presence of C. trachomatis DNA . Prevalence of active trachoma was 6.7 % ( 335/5033 ) in The Gambia and 32.3 % ( 1008/3122 ) in Tanzania . The countries ' corresponding Amplicor positive prevalences were 0.8 % and 21.9 % . After adjustment , risk factors for follicular trachoma ( TF ) in both countries were ocular or nasal discharge , a low level of household head education , and being aged ≥ 1 year . Additional risk factors in Tanzania were flies on the child 's face , being Amplicor positive , and crowding ( the number of children per household ) . The risk factors for being Amplicor positive in Tanzania were similar to those for TF , with the exclusion of flies and crowding . In The Gambia , only ocular discharge was associated with being Amplicor positive . CONCLUSIONS/SIGNIFICANCE These results indicate that although the prevalence of active trachoma and Amplicor positives were very different between the two countries , the risk factors for active trachoma were similar but those for being Amplicor positive were different . The lack of an association between being Amplicor positive and TF in The Gambia highlights the poor correlation between the presence of trachoma clinical signs and evidence of C. trachomatis infection in this setting . Only ocular discharge was associated with evidence of C. trachomatis DNA in The Gambia , suggesting that at this low endemicity , this may be the most important risk factor . TRIAL REGISTRATION ClinicalTrials.gov NCT00792922 .

trachoma

ocular C. trachomatis infection

ocular swab

Amplicor polymerase chain reaction

Amplicor positive prevalences

ocular or nasal discharge

low level of household head education

children

0-5 years


Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation . BACKGROUND A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator ( CFTR ) . VX-770 , a CFTR potentiator , has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro . METHODS We randomly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25 , 75 , or 150 mg or placebo for 14 days ( in part 1 of the study ) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days ( in part 2 of the study ) . RESULTS At day 28 , in the group of subjects who received 150 mg of VX-770 , the median change in the nasal potential difference ( in response to the administration of a chloride-free isoproterenol solution ) from baseline was -3.5 mV ( range , -8.3 to 0.5 ; P=0.02 for the within-subject comparison , P=0.13 vs. placebo ) , and the median change in the level of sweat chloride was -59.5 mmol per liter ( range , -66.0 to -19.0 ; P=0.008 within-subject , P=0.02 vs. placebo ) . The median change from baseline in the percent of predicted forced expiratory volume in 1 second was 8.7 % ( range , 2.3 to 31.3 ; P=0.008 for the within-subject comparison , P=0.56 vs. placebo ) . None of the subjects withdrew from the study . Six severe adverse events occurred in two subjects ( diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes ) . All severe adverse events resolved without the discontinuation of VX-770 . CONCLUSIONS This study to evaluate the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function . These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis . ( Funded by Vertex Pharmaceuticals and others ; ClinicalTrials.gov number , NCT00457821 . ) .

oral VX-770

placebo

nasal potential difference

level of sweat chloride

forced expiratory volume

severe adverse events

diffuse macular rash

elevated blood and urine glucose levels

diabetes

safety

adverse-event profile

CFTR

lung function


Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer . BACKGROUND Safety and efficacy of gemcitabine plus docetaxel ( GD ) and capecitabine plus docetaxel ( CD ) were compared in patients with metastatic breast cancer , where the alternate crossover monotherapy ( GD→C or CD→G ) was predetermined . PATIENTS AND METHODS Patients were randomly assigned to 3-week cycles of either gemcitabine 1000 mg/m ( 2 ) on days 1 and 8 plus docetaxel 75 mg/m ( 2 ) on day 1 or capecitabine 1000 mg/m ( 2 ) twice daily on days 1-14 plus docetaxel 75 mg/m ( 2 ) day 1 . Upon progression , patients received crossover monotherapy . Primary end point was time to progression ( TtP ) . Secondary end points evaluated overall response rate ( ORR ) , overall survival ( OS ) , and adverse events ( AEs ) . RESULTS Despite over-accrual of 475 patients , the trial matured with only 324 of 385 planned TtP events due to patient discontinuations . Human epidermal growth factor receptor 2 status was not captured in this study . More CD patients ( 28 % ) discontinued due to AEs than GD patients ( 18.0 % , P = 0.009 ) . TtP [ hazard ratio ( HR ) = 1.101 , 95 % confidence interval ( CI ) 0.885-1.370 , P = 0.387 ] and OS ( HR = 1.031 , 95 % CI 0.830-1.280 , P = 0.785 ) were not significantly different comparing GD and CD . ORR was not statistically different ( P = 0.239 ) comparing GD ( 72 of 207 , 34.8 % ) and CD ( 78 of 191 , 40.8 % ) . TtP , OS , and ORR were not significantly different comparing crossover groups . GD caused greater fatigue , hepatotoxicity , neutropenia , and thrombocytopenia but not febrile neutropenia ; CD caused more hand-foot syndrome , gastrointestinal toxicity , and mucositis . CONCLUSIONS GD and CD produced similar efficacy and toxicity profiles consistent with prior clinical experience .

gemcitabine plus docetaxel

capecitabine plus docetaxel

gemcitabine plus docetaxel ( GD )

capecitabine plus docetaxel ( CD )

Safety and efficacy

metastatic breast cancer .

metastatic breast cancer

324 of 385


A placebo-controlled , randomized clinical trial using testosterone undecanoate with injectable norethisterone enanthate : effect on anthropometric , metabolic and biochemical parameters . Testosterone administered alone or in combination with progestogens in male contraception induces reversible oligo-azoospermia , but its effects on body composition and metabolism are less known . We analysed anthropometric and metabolic parameters in five groups of 10 males : four receiving testosterone undecanoate ( TU : 1000 mg ) plus norethisterone enanthate ( NETE : 200 mg ) at different intervals ( every 8 weeks : NETE-8 ; every 12 weeks : NETE-12 ; every 6 weeks for 12 weeks and then every 12 weeks : NETE-6/12 ; every 6 weeks for 12 weeks and then TU plus placebo every 12 weeks : NETE-6/12/0 ) and one placebo ( NETE-0/0 ) for a total of 48 weeks . Body mass index ( BMI ) and waist circumference did not change in any groups except for the NETE-8 in which BMI increased significantly ( p = 0.02 ) at the end of the treatment period . Lean body mass ( MAMC or AMA ) increased significantly in the highest hormonal dose groups ( p = 0.04 , NETE-6/12 ; p = 0.004 , NETE-8 ) . No differences were observed in glucose levels , insulin sensitivity index and lipid profile as well as in biochemical and cell count parameters in any groups . In conclusion , NETE and TU for 48 weeks were not accompanied by any metabolic changes and any adverse effects . The weight gain of the highest NETE plus TU dosage was mainly because of gain in muscle mass .

placebo-controlled

testosterone undecanoate

plus norethisterone enanthate

TU plus placebo

placebo

BMI increased significantly

biochemical and cell count parameters

metabolic changes and any

adverse effects

weight gain


The effect of HCG supplementation after combined GnRH agonist/HMG treatment in an IVF programme . The necessity of luteal-phase supplementation in an IVF programme is of continuing interest . After ovarian stimulation with clomiphene and human menopausal gonadotrophin ( HMG ) , the beneficial effect of supporting the luteal phase has never been scientifically demonstrated . After ovarian stimulation with GnRH agonist/HMG , the luteal phase seems to be inadequate , but in a previous study we did not find evidence to support the need for oral progesterone supplementation . To evaluate the beneficial effect of human chorionic gonadotrophin ( HCG ) supplementation , we performed a multicentre , double-blind , randomized study with HCG ( 193 transfers ) against placebo ( 194 transfers ) . The ongoing pregnancy rate per transfer cycle was significantly better with HCG ( 18.7 versus 9.3 ) . This is the first truly objective ( randomized ) study demonstrating the beneficial effect of supporting the luteal phase in an IVF programme .

HCG supplementation

combined GnRH agonist/HMG treatment

luteal-phase supplementation

human menopausal gonadotrophin ( HMG )

GnRH agonist/HMG

HCG

placebo

HCG

treatment in an IVF programme .

IVF programme .


Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma . Blockade of cytotoxic T-lymphocyte antigen-4 ( CTLA-4 ) by ipilimumab leads to immune-mediated tumor regression and immune-related adverse events ( irAEs ) , including diarrhea and colitis . The current analyses were undertaken to promote an understanding of the underlying mechanism of action and to identify potential biomarkers that could help in the prediction and management of ipilimumab-induced gastrointestinal irAEs . Treatment-naïve or previously treated patients with unresectable stage III/IV melanoma ( n = 115 ) received open-label ipilimumab ( 10 mg/kg every 3 weeks for four doses ) and were randomized to receive concomitant blinded prophylactic oral budesonide ( 9 mg/d with gradual taper through week 16 ) or placebo . Outcome measures included histologic assessment of bowel biopsies and assessment of serologic markers of inflammatory bowel disease ( IBD ) , fecal calprotectin levels , and polymorphisms in immune-related genes . Ipilimumab resulted in dysregulation of gastrointestinal mucosal immunity as evidenced by altered antibody levels to enteric flora , inflammatory cell infiltration into gastrointestinal mucosa , and increased fecal calprotectin associated with diarrhea and clinical evidence of colitis . The pattern of ipilimumab-induced antibody titers to microbial flora and the histologic features and location of the inflammation were distinct from classic IBD . Prophylactic budesonide did not prevent ipilimumab-induced bowel inflammation . Despite an observed association between colonic inflammation and grade 2 or higher diarrhea , no baseline biomarkers could reliably predict development of gastrointestinal toxicity . Although classic IBD and ipilimumab-related gastrointestinal toxicity are both immune mediated , the observed pattern of biomarkers suggests ipilimumab-related gastrointestinal toxicity may be a distinct clinicopathologic entity .

ipilimumab

histologic assessment of bowel biopsies

fecal calprotectin levels

polymorphisms in immune-related genes

levels to enteric flora

inflammatory cell infiltration

fecal calprotectin

diarrhea

colitis

diarrhea

melanoma


A pilot study of the Tele-Airway Management System in a hospital emergency department . We developed a telemedicine system for remote guidance of emergency airway management called the Tele-Airway Management System ( TAMS ) . In a pilot study we examined the usefulness of the TAMS for intubations of actual patients in a hospital emergency department . Twenty-five patients were allocated randomly either to a TAMS group or to an on-scene directed ( OSD ) group . A total of 12 were intubated using the TAMS . The mean time to intubation ( TAMS 62 s vs. OSD 56 s ) and the success rate was not different between the two groups ( P > 0.05 ) . There were two oesophageal intubations in the TAMS group and four in the OSD group , but this was not significantly different ( P = 0.36 ) . There were no mechanical or technical errors such as disconnection during use of the TAMS . The pilot study demonstrated the feasibility of the TAMS as an alternative to OSD . However , a larger study will be required to determine non-superiority or equivalence .

Tele-Airway Management System

Tele-Airway Management System

TAMS

TAMS group

on-scene directed ( OSD ) group

TAMS

TAMS

OSD

TAMS

OSD

TAMS

OSD

mean time to intubation

success rate

oesophageal intubations

feasibility

Twenty-five


Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise . Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate ( glucose+1/2 lactate ) and metabolic acidosis appears to promote cerebral lactate uptake . However , the influence of pH on cerebral lactate uptake and , in turn , on the cerebral metabolic ratio during exercise is not known . Sodium bicarbonate ( Bicarb , 1 M ; 350-500 ml ) or an equal volume of normal saline ( Sal ) was infused intravenously at a constant rate during a '2000 m ' maximal ergometer row in six male oarsmen ( 23±2 years ; mean±S.D. ) . During the Sal trial , pH decreased from 7.41±0.01 at rest to 7.02±0.02 but only to 7.36±0.02 ( P < 0.05 ) during the Bicarb trial . Arterial lactate increased to 21.4±0.8 and 32.7±2.3 mM during the Sal and Bicarb trials , respectively ( P < 0.05 ) . Also , the arterial-jugular venous lactate difference increased from-0.03±0.01 mM at rest to 3.2±0.9 mM ( P < 0.05 ) and 3.4±1.4 mM ( P < 0.05 ) following the Sal and Bicarb trials , respectively . Accordingly , the cerebral metabolic ratio decreased equally during the Sal and Bicarb trials : from 5.8±0.6 at rest to 1.7±0.1 and 1.8±0.2 , respectively . The enlarged blood-buffering capacity after infusion of Bicarb eliminated metabolic acidosis during maximal exercise but that did not affect the cerebral lactate uptake and , therefore , the decrease in the cerebral metabolic ratio .

Sodium bicarbonate

normal saline

ergometer row

promote cerebral lactate uptake

pH

Arterial lactate

cerebral metabolic ratio


The Toronto prehospital hypertonic resuscitation -- head injury and multiorgan dysfunction trial : feasibility study of a randomized controlled trial . OBJECTIVE The aim of the study was to evaluate the feasibility of a prehospital trial comparing hypertonic saline and dextran ( HSD ) with normal saline ( NS ) in blunt head injury patients . DESIGN The study used a double blind randomized trial . SETTING The study was conducted in air and land emergency medical services and 2 trauma centers serving a population of 4 million people . PATIENTS The study population consisted of head injured , blunt trauma adult patients with a Glasgow Coma Scale of lower than 9 . INTERVENTIONS We used 250 mL of HSD vs NS given within 4 hours of the accident . MEASUREMENTS The specific objectives were to assess protocol-related logistical issues , randomization , HSD safety , and follow up rates and to obtain survival and neurocognitive end point estimates . MAIN RESULTS Of 132 eligible patients , 113 were randomized . Nineteen eligible patients were missed because of lack of time ( 9 [ 22 % ] ) , paramedic discretion ( 3 [ 7 % ] ) , the paramedic forgot ( 6 [ 15 % ] ) , and the paramedic refused ( 1 [ 2 % ] ) . Randomization compliance was 96 % ( 109/113 ) . Four randomized cases met exclusion criteria : penetrating trauma ( 1 ) , cardiac arrest ( 2 ) , and fall from standing ( 1 ) . Three randomized patients were excluded from the final analysis : 2 patients received less than 50 mL of study solution due to an interstitial intravenous line and 1 lost randomization identification . Fifty patients ( 47 % ) were randomized to HSD and 56 ( 53 % ) to NS . Mean injury severity score was 32.7 for HSD and 32.6 for NS . There was no difference in length of stay , Sequential Organ Failure Assessment maximum , Multiple Organ Dysfunction Score maximum , delta Multiple Organ Dysfunction Score , or Apache scores . Initial head scans scored 3 or higher by Marshall classification for 12 HSD and 11 NS patients . Zero adverse events occurred , and follow-up for the primary outcome was 100 % . Alive at 30 days for HSD and NS , respectively , was 70 % ( 35/50 ) and 75 % ( 42/56 ) and at discharge was 68 % ( 34/50 ) and 73 % ( 41/56 ) . Only 49.3 % ( 37/77 ) of surviving patients consented to follow-up at 4 months and 89 % ( 33/37 ) completed the assessment . Disability rating scale ( median , interquartile range ) was 3 ( 0 , 6 ) for HSD and was 0 ( 0 , 6 ) for NS . Glasgow Outcome Scale Evaluation was higher than 4 for HSD ( 12/12 [ 100 % ] ) and NS ( 15/21 [ 72 % ] ) . Functional Independence Measure ( mean , SD ) was 62 ( 37 ) for HSD and 80 ( 32 ) for NS . CONCLUSIONS It is feasible to conduct a prehospital randomized controlled trial with HSD for treatment of blunt trauma patients with head injuries ; however , consent for neurofunctional outcomes in this cohort is problematic and threatens the feasibility of definitive trials using these potentially meaningful end points .

hypertonic saline and dextran ( HSD )

normal saline ( NS

250 mL of HSD

NS

HSD

randomization

HSD safety ,

follow up rates

survival

neurocognitive end point estimates

Mean injury severity score

length of stay

Initial head scans

adverse events

Alive at 30 days

Disability rating scale

Glasgow Outcome Scale Evaluation

Functional Independence Measure

resuscitation -- head

4 million people .

adult

Glasgow Coma

132 eligible patients


Inhibin A is down-regulated during chemotherapy in patients with breast cancer . BACKGROUND Inhibins are dimeric glycoproteins , composed of an alpha-subunit ( INH-α ) and one of two possible beta-subunits ( βA or βB ) , with substantial roles in human reproduction and in endocrine-responsive tumours . Aims of this study were to determine the serological measurement of inhibin A ( α-βA ) in breast cancer patients during chemotherapy . PATIENTS AND METHODS A series of 30 breast cancer patients who underwent standardised chemotherapy were prospectively evaluated before chemotherapeutic treatment as well as four weeks after chemotherapy and two years after chemotherapy for the serological expression of inhibin A . For statistical analysis the Wilcoxon rank sum test was used for paired samples . Statistical significance was assumed at p < 0.05 . RESULTS The concentration of inhibin A showed a significant decrease between data obtained before chemotherapy and after chemotherapy ( p < 0.005 ) and two-year follow-up ( p < 0.001 ) . Interestingly , there were no differences in inhibin A concentrations between the four-week and two-year follow-up ( p=0.744 ) . DISCUSSION Chemotherapy significantly decreases inhibin A concentration during chemotherapy . This might reflect a suppression of ovarian function , being also a marker for chemotherapy-induced amenorrhoea . Moreover , it has been suggested that inhibin A might be a tumour marker for breast cancer , and therefore a sudden increase in its concentration might be indicative of breast cancer recurrence .

chemotherapy

inhibin A ( α-βA )

breast cancer

breast cancer

breast cancer


Removal of humoral mediators and the effect on the survival of septic patients by hemoperfusion with neutral microporous resin column . The aim of this study is to evaluate the impact of neutral microporous resin hemoperfusion on hemodynamic improvement , removal of inflammatory cytokines , and mortality in critical care patients with severe sepsis . Forty-four patients with severe sepsis or septic shock were randomized to HA type hemoperfusion treatment ( N=24 ) or standard therapy ( N=20 ) . Those undergoing hemoperfusion treatment received HA330 hemoperfusion . We measured the plasma concentrations of IL-6 and IL-8 at the start of every hemoperfusion treatment , and the following parameters were compared between the control group and the hemoperfusion group on days 3 , 7 , and 14 : hemodynamics ( cardiac index , systemic vascular resistance index , heart rate , and mean arterial pressure ) ; change of hematology and coagulation function ; organ function ; and the sequential organ failure assessment ( SOFA ) score . Hospital , 28-day , and ICU mortality were also observed . Patients treated with HA hemoperfusion showed a significant removal of plasma IL-6 and IL-8 over time while in the study . Patients in the HA group also demonstrated significant increases in cardiac index , systemic vascular resistant index , fast withdrawal of vasoactive agents and decreases in heart rate compared with the controls at days 3 and 7 . Although there was no significant difference between the groups in organ dysfunction as assessed by SOFA scores from day 0 ( baseline ) to day 7 , significant improvement can be demonstrated in the hemoperfusion group at day 14 . There was no significant difference between the groups in 28-day mortality , hospital mortality , or length of hospital stay , but ICU mortality and the length of ICU stay in the HA group were markedly reduced . Hemoperfusion treatment using the HA type cartridge in sepsis is safe and it may improve organ dysfunction , ICU mortality , and shorten the length of ICU stay . Clinical significant removal of inflammatory cytokines such as IL-6 and IL-8 from circulation by hemoperfusion may contribute to improving a patient 's outcome in an ICU .

hemoperfusion

neutral microporous resin hemoperfusion

HA type hemoperfusion treatment

HA330 hemoperfusion

hemoperfusion

HA hemoperfusion

hemoperfusion

plasma concentrations of IL-6

organ function

Hospital , 28-day , and ICU mortality

plasma IL-6

significant increases

significant difference

organ dysfunction

SOFA scores

significant difference

reduced .

septic

severe sepsis .

Forty-four

severe sepsis or septic shock


A two-part phase II study of cediranib in patients with advanced solid tumours : the effect of food on single-dose pharmacokinetics and an evaluation of safety , efficacy and imaging pharmacodynamics . BACKGROUND Cediranib ( RECENTIN™ ) is an oral , highly potent VEGF inhibitor . This study evaluated the effect of food on the pharmacokinetics of cediranib and compared the administration of continual cediranib via two dosing strategies using this as a platform to investigate pharmacodynamic imaging biomarkers . METHODS Sixty patients were randomised to receive two single doses of cediranib in either fed/fasted or fasted/fed state ( Part A ) . In continual dosage phase ( Part B ) , patients were randomised to a fixed-dose or dose-escalation arm . Exploratory pharmacodynamic assessments were performed using DCE-MRI and CT enhancing fraction ( EnF ) . RESULTS In part A , plasma AUC and C ( max ) of cediranib were lower in the presence of food by a mean of 24 and 33 % , respectively ( 94 % CI : AUC , 12-34 % and C ( max ) , 20-43 % ) , indicating food reduces cediranib plasma exposure . In part B , cediranib 30 mg/day appeared to be the most sustainable for chronic dosing . Continuous cediranib therapy was associated with sustained antivascular effects up to 16 weeks , with significant reductions in DCE-MRI parameters and CT EnF . CONCLUSIONS It is recommended that cediranib be administered at least 1 h before or 2 h after food . Evidence of antitumour activity was observed , with significant sustained effects upon imaging vascular parameters .

cediranib

safety

efficacy

imaging pharmacodynamics

plasma AUC and C ( max ) of cediranib

sustained antivascular effects

DCE-MRI parameters and CT

advanced solid tumours

Sixty patients


[ GISSI-2 ; the beginning of the end or the end of the beginning for tissue plasminogen activator in acute myocardial infarct ? ] .

tissue plasminogen

acute myocardial infarct

acute myocardial infarct


Intervention targeting development of socially synchronous engagement in toddlers with autism spectrum disorder : a randomized controlled trial . BACKGROUND Social and communication impairments are core deficits and prognostic indicators of autism . We evaluated the impact of supplementing a comprehensive intervention with a curriculum targeting socially synchronous behavior on social outcomes of toddlers with autism spectrum disorders ( ASD ) . METHODS Fifty toddlers with ASD , ages 21 to 33 months , were randomized to one of two six-month interventions : Interpersonal Synchrony or Non-Interpersonal Synchrony . The interventions provided identical intensity ( 10 hours per week in classroom ) , student-to-teacher ratio , schedule , home-based parent training ( 1.5 hours per month ) , parent education ( 38 hours ) , and instructional strategies , except the Interpersonal Synchrony condition provided a supplementary curriculum targeting socially engaged imitation , joint attention , and affect sharing ; measures of these were primary outcomes . Assessments were conducted pre-intervention , immediately post-intervention , and , to assess maintenance , at six-month follow-up . Random effects models were used to examine differences between groups over time . Secondary analyses examined gains in expressive language and nonverbal cognition , and time effects during the intervention and follow-up periods . RESULTS A significant treatment effect was found for socially engaged imitation ( p = .02 ) , with more than doubling ( 17 % to 42 % ) of imitated acts paired with eye contact in the Interpersonal Synchrony group after the intervention . This skill was generalized to unfamiliar contexts and maintained through follow-up . Similar gains were observed for initiation of joint attention and shared positive affect , but between-group differences did not reach statistical significance . A significant time effect was found for all outcomes ( p < .001 ) ; greatest change occurred during the intervention period , particularly in the Interpersonal Synchrony group . CONCLUSIONS This is the first ASD randomized trial involving toddlers to identify an active ingredient for enhancing socially engaged imitation . Adding social engagement targets to intervention improves short-term outcome at no additional cost to the intervention . The social , language , and cognitive gains in our participants provide evidence for plasticity of these developmental systems in toddlers with ASD . http : //www.clinicaltrials.gov/ct2/show/NCT00106210 ? term = landa & rank = 3 .

Intervention

comprehensive intervention

Interpersonal Synchrony

Non-Interpersonal Synchrony .

joint attention


Human psychopharmacology and dose-effects of salvinorin A , a kappa opioid agonist hallucinogen present in the plant Salvia divinorum . Salvinorin A is a potent , selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum , a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing . S. divinorum has over the last several years gained increased popularity as a recreational drug . This is a double-blind , placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults . Across sessions , participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions . Doses ranged from 0.375 μg/kg to 21 μg/kg . Subject-rated drug strength was assessed every 2 min for 60 min after inhalation . Orderly time- and dose-related effects were observed . Drug strength ratings peaked at 2 min ( first time point ) and definite subjective effects were no longer present at approximately 20 min after inhalation . Dose-related increases were observed on questionnaire measures of mystical-type experience ( Mysticism Scale ) and subjective effects associated with classic serotonergic ( 5-HT2 ( A ) ) hallucinogens ( Hallucinogen Rating Scale ) . Salvinorin A did not significantly increase heart rate or blood pressure . Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals ( e.g. , change in spatial orientation , pressure on the body ) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories , cartoon-like imagery , and contact with entities . Under these prepared and supportive conditions , salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens , including mystical-type effects .

salvinorin A

Salvinorin A

placebo

salvinorin A

salvinorin A

intermixed placebo

inhalation

blood pressure

healthy hallucinogen-using

adults


Mechanisms underlying the lack of effect of implantable cardioverter-defibrillator therapy on mortality in high-risk patients with recent myocardial infarction : insights from the Defibrillation in Acute Myocardial Infarction Trial ( DINAMIT ) . BACKGROUND although implantable cardioverter-defibrillators ( ICDs ) lower mortality in stable patients with low ejection fraction late after myocardial infarction , randomized trials of ICD versus control subjects implanted early after myocardial infarction do not show mortality benefit . Our objective was to investigate possible mechanisms underlying the lack of mortality benefit in the Defibrillation in Acute Myocardial Infarction Trial ( DINAMIT ) . METHODS AND RESULTS this is a secondary analysis of the prospective randomized clinical trial . Outpatients with recent ( 6 to 40 days ) acute myocardial infarction , left ventricular dysfunction ( ejection fraction < 35 % ) , and low heart rate variability were randomized to ICD ( n=311 ) or to standard medical therapy ( n=342 ) . In a competing-risks analysis , those factors that increased the risk of arrhythmic death also increased the risk of nonarrhythmic deaths . After adjustment for these factors , receiving an ICD was associated with a decreased risk of arrhythmic death ( hazard ratio , 0.33 ; 95 % confidence interval , 0.15 to 0.71 ) but an increase in nonarrhythmic death ( hazard ratio , 1.70 ; 95 % confidence interval , 1.00 to 2.80 ) . In an adjusted time-dependent analysis , patients receiving an ICD and having appropriate ICD therapy had a 15.1 % yearly hazard of mortality compared with 5.2 % in ICD patients with no appropriate therapy ( P < 0.001 ) . The reduction in sudden death in ICD patients was completely offset by increased nonarrhythmic deaths , which were greatest in patients receiving ICD shock therapy ( hazard ratio , 6.0 ; 95 % confidence interval , 2.8 to 12.7 ) . CONCLUSIONS in patients receiving ICDs early after myocardial infarction , those factors that are associated with arrhythmia requiring ICD therapy are also associated with a high risk of nonsudden death , negating the benefit of ICDs in this setting .

implantable cardioverter-defibrillators

ICD

ICD

standard medical therapy

mortality

mortality

risk of arrhythmic death

risk of nonarrhythmic deaths

risk of arrhythmic death

nonarrhythmic death

yearly hazard of mortality

sudden death

nonarrhythmic deaths

nonsudden death

recent myocardial infarction


Effects of the 810-nm diode laser on hair and on the biophysical properties of skin . INTRODUCTION Laser therapy is clinically effective in hair removal ; however , despite the development of various strategies , laser procedures still present a risk of adverse effects due to the overheating of the skin . OBJECTIVE To investigate the effects of 810-nm diode laser treatment on hair and on the biophysical properties of skin by using various non-invasive techniques on various parameters , including hair analysis , surface color changes , integrity of skin barrier , sebum production rate and pH level . METHODS In this randomized , right-left comparison study , 35 women with axillary hair received single-session diode laser therapy . Hair analysis and biophysical properties of the skin were assessed before treatment and at weeks 2 , 4 and 6 after the therapy . RESULTS Hair density and thicknesses statistically significantly decreased after the first post-treatment evaluation . Regarding comparison of the biophysical properties of the skin , there was no statistically significant difference in the assessments , except for the increase determined during the second week in the erythema index in the laser-treated areas . CONCLUSION The findings of this study showed that the diode laser can perform a significant reduction in the hair amount without significant epidermal damage , at least for a short period .

810-nm diode laser

Laser therapy

810-nm diode laser treatment

non-invasive techniques

single-session diode laser therapy

diode laser can

Hair density and thicknesses

erythema index

hair amount

35 women with axillary hair


Right ventricular pacing in MADIT-II : a risk factor for increased mortality , or mainly a marker of increased risk .

Right ventricular pacing

mortality

marker of increased risk .

Right ventricular pacing in MADIT-II :


Randomized trial of angiotensin II-receptor blocker vs. dihydropiridine calcium channel blocker in the treatment of paroxysmal atrial fibrillation with hypertension ( J-RHYTHM II study ) . AIMS Atrial fibrillation ( AF ) is a common arrhythmia frequently associated with hypertension . This study was designed to test the hypothesis that lowering blood pressure by angiotensin II-receptor blockers ( ARB ) has more beneficial effects than by conventional calcium channel blockers ( CCB ) on the frequency of paroxysmal AF with hypertension . METHODS AND RESULTS The Japanese Rhythm Management Trial II for Atrial Fibrillation ( J-RHYTHM II study ) is an open-label randomized comparison between an ARB ( candesartan ) and a CCB ( amlodipine ) in the treatment of paroxysmal AF associated with hypertension . Using daily transtelephonic monitoring , we examined asymptomatic and symptomatic paroxysmal AF episodes during a maximum 1 year treatment . The primary endpoint was the difference in AF frequency between the pre-treatment period and the final month of the follow-up . The secondary endpoints included cardiovascular events , development of persistent AF , left atrial dimension , and quality-of-life ( QOL ) . The study enrolled 318 patients ( 66 years , male/female 219/99 , 158 in the ARB group and 160 in the CCB group ) treated at 48 sites throughout Japan . At baseline , the frequency of AF episodes ( days/month ) was 3.8 ± 5.0 in the ARB group vs. 4.8 ± 6.3 in the CCB group ( not significant ) . During the follow-up , blood pressure was significantly lower in the CCB group than in the ARB group ( P < 0.001 ) . The AF frequency decreased similarly in both groups , and there was no significant difference in the primary endpoint between the two groups . There were no significant differences between the two groups in the development of persistent AF , changes in left atrial dimension , occurrence of cardiovascular events , or changes in QOL . CONCLUSIONS In patients with paroxysmal AF and hypertension , treatment of hypertension by candesartan did not have an advantage over amlodipine in the reduction in the frequency of paroxysmal AF ( umin CTR C000000427 ) .

angiotensin II-receptor blocker

dihydropiridine calcium channel blocker

ARB ( candesartan )

CCB ( amlodipine )

ARB

CCB

paroxysmal AF

difference in AF frequency

cardiovascular events

development of persistent AF

left atrial dimension

quality-of-life ( QOL )

frequency of AF episodes

66 years

male/female


Cost-effectiveness of ablation surgery in patients with atrial fibrillation undergoing cardiac surgery . This study was performed to assess the cost-effectiveness of concomitant ablation surgery ( AS ) compared to regular cardiac surgery in atrial fibrillation ( AF ) patients over a one-year follow-up . Cost analysis was performed from a societal perspective alongside a prospective , randomised , double-blinded , multicentre trial . One hundred and fifty patients with documented AF were randomly assigned to undergo cardiac surgery with or without AS . One hundred and thirty-two patients were included in the cost-effectiveness study . All costs ( medical and non-medical ) were measured during follow-up . Costs data were combined with quality adjusted life years ( QALYs ) to obtain the incremental costs per QALY . Total costs of the AS group were significantly higher compared to the regular cardiac surgery group [ cost difference bootstrap : €4,724 ; 95 % uncertainty interval ( UI ) , €2,770-€6,678 ] . The bootstrapped difference in QALYs was not statistically significant ( 0.06 ; 95 % UI : -0.024 to 0.14 ) . The incremental cost-effectiveness ratio is €73,359 per QALY . The acceptability curve showed that , even in the case of a maximum threshold value of €80,000 per QALY gained , the probability of AS being more cost-effective than regular cardiac surgery did not reach beyond 50 % . Concluding that concomitant AS in AF is not cost-effective after a one-year follow-up compared to regular cardiac surgery .

ablation surgery

ablation surgery ( AS )

cardiac surgery

AS

Cost-effectiveness

Cost analysis

All costs ( medical and non-medical )

Costs data

quality adjusted life years

Total costs


Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction . BACKGROUND The effect of L-arginine and L-citrulline on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction ( HFpEF ) is unknown . We have therefore evaluated , in a randomized clinical trial , the effect of these aminoacids in chronic outstanding and stable patients with HFpEF . METHODS AND RESULTS All patients underwent an echocardiogram and radioisotopic ventriculography rest/exercise , and were randomized in a consecutive manner to the L-arginine group ( n = 15 ; 8 g/day ) ; and the citrulline malate group ( n = 15 ; 3 g/day ) . The duration of follow-up was two months . The principal echocardiographic finding was a statistically significant decrease in pulmonary artery pressure in the L-arginine ( 56.3 ± 10 vs 44 ± 16.5 mm Hg , p < 0.05 ) and the citrulline ( 56.67 ± 7.96 vs 47.67 ± 8.59 mm Hg , p < 0.05 ) groups . Duration on treadmill and right ventricular ejection fraction post exercise increased , while diastolic and systolic artery pressure decreased significantly in both groups . There were no other statistically significant differences between the groups . CONCLUSIONS Administration of L-arginine and citrulline to patients with HFpEF improved right ventricular function by increasing right ventricular ejection fraction , and probably decreasing systolic pulmonary artery pressure .

L-arginine

L-citrulline oral supplementation

L-arginine

L-citrulline

L-arginine group

citrulline malate group

L-arginine

blood pressure

right ventricular function

blood pressure

right ventricular function

pulmonary artery pressure

heart failure

preserved ejection fraction

HFpEF


Cost effectiveness of training incontinent elderly in nursing homes : a randomized clinical trial . This study used a randomized clinical trial with 133 incontinent elderly in seven nursing homes to evaluate the effectiveness of a behavioral training therapy and its cost implications . The training program lasted three months , and a 22-week follow-up period examined the durability of the treatment effect . The therapy became effective after six weeks of training . By the final months of training , the treatment participants ' wet episodes had been reduced by 0.6 episode per day , or a 26 percent reduction over baseline , and improvement was maintained during the follow-up period . Trainees with a high frequency of incontinence during baseline , relatively more cognitive residents , and residents with a normal bladder capacity responded better to this behavioral program . The cost of training was the equivalent of about one hour of nursing aide time per patient day . The reduction in incontinence during the follow-up period resulted in some small savings in laundry costs and supplies used , and some quantitatively unmeasurable but detectable improvement in psychosocial well-being among the trainees . Since the central figure in implementing this training protocol is the nursing aide , it is important to find an organizational management scheme that will stimulate nursing aides to reduce incontinence among nursing home residents .

behavioral training therapy

behavioral program

effectiveness

wet episodes

cost of training

incontinence

improvement in psychosocial well-being

incontinent

elderly

in nursing homes :

incontinent

elderly

incontinence


[ Accelerated postoperative radiotherapy in patients with advanced larynx cancer ] . AIM The aim of study was test efficacy of accelerated postoperative radiotherapy -- concomitant boost in patients with advanced larynx cancer . METHODS AND MATERIALS The prospective study included 112 patients with advanced larynx cancer after radical surgical treatment . Patients had postoperative radiation therapy , conventional ( C ) or accelerated ( CB ) . RESULTS The 3-year overall survival in CB was 59 % , in C -- 58 % ( p = 0.2 ) , 3-year locoregional control in CB -- 83 % , in C -- 75 % ( p = 0.01 ) , the 3-year disease free survival was in CB -- 72 % , C -- 66 % ( p = 0.1 ) . CONCLUSION Concomitant boost postoperative radiation therapy did not improve overall survival , loco-regional control , disease free survival . Patients with close surgical margins , longer interval between surgery and radiation , high level of hemoglobin , T4 had benefit from accelerated radiotherapy .

Accelerated postoperative radiotherapy

radical surgical treatment

postoperative radiation therapy

conventional ( C )

accelerated ( CB )

CB

CB

CB

accelerated radiotherapy

efficacy

3-year overall survival

3-year locoregional control

3-year disease free survival

overall survival

loco-regional control

disease free survival

patients with advanced larynx cancer

patients with advanced larynx cancer

112 patients

Patients with close surgical margins


Relationship between baseline blood pressure parameters ( including mean pressure , pulse pressure , and variability ) and early outcome after stroke : data from the Tinzaparin in Acute Ischaemic Stroke Trial ( TAIST ) . BACKGROUND AND PURPOSE High blood pressure ( BP ) in acute stroke is associated independently with a poor outcome . Recent evidence suggests that other hemodynamic parameters may also be associated with outcomes following stroke . METHODS The relationship between baseline BP , heart rate , and other hemodynamic parameters , and early outcomes were assessed using data from TAIST trial . RESULTS Death or neurological deterioration at day 10 was associated , both in unadjusted and adjusted analyses , with systolic BP ( adjusted OR , 1.02 ; 95 % CI , 1.01-1.03 ) , mean arterial pressure ( OR , 1.02 ; 95 % CI , 1.01-1.04 ) , pulse pressure ( OR , 1.02 ; 95 % CI , 1.01-1.03 ) , and BP variability ( OR , 1.03 ; 95 % CI , 1.01-1.05 ) . Similar relationships were noted for deterioration alone , and recurrent stroke . CONCLUSIONS Early death or neurologic deterioration , deterioration , and recurrent stroke are associated independently with high systolic BP , mean arterial pressure , pulse pressure , and BP variability . These measures offer potential therapeutic targets for improving early outcome after acute ischemic stroke .

Tinzaparin

therapeutic targets

Death

neurological deterioration at day 10

systolic BP

mean arterial pressure

pulse pressure

BP variability

deterioration alone

recurrent stroke

death

neurologic deterioration

deterioration

recurrent stroke

high systolic BP

mean arterial pressure

pulse pressure

BP variability

stroke

Acute Ischaemic Stroke

High blood pressure

acute stroke

high systolic BP

BP

acute ischemic stroke


Differential effects of vitamin K1 on AFP and DCP levels in patients with unresectable HCC and in HCC cell lines . PURPOSE DCP is a useful HCC tumor marker , which reflects a defect in vitamin K metabolism . We tested the hypothesis that vitamin K treatment of HCC patients might suppress this marker and possibly AFP also . EXPERIMENTAL DESIGN HCC patients who had both elevated AFP and DCP were included . A phase I cohort was treated with escalating vitamin K1 intravenous weekly doses and a 27-patient phase II cohort was then treated with a fixed oral daily dose . RESULTS A maximum tolerated dose was not reached up to 100-fold the normal vitamin K1 dose . No toxicities were found up to 1,000 mg/infusion . In the phase II cohort , 93 % of patients had tumor marker responses by decreased DCP levels , but only 22 % had responses by decreased AFP levels . CT scans showed 11 % of patients had PRs , 59 % had stable tumors and 29.6 % had tumor progression . Mechanism studies showed that vitamin K1 induced phosphorylation of JNK and c-Jun and caspase-mediated apoptosis . CONCLUSIONS Vitamin K1 was non-toxic at high doses , strongly inhibited plasma DCP levels , but weakly suppressed AFP levels . The results provide evidence that the two tumor markers are not directly linked and that DCP levels may not reflect HCC cell growth , as DCP levels were decreased in patients without AFP change , and were suppressed in vitro at 1 % of the vitamin K1 concentration needed to inhibit AFP .

vitamin K1

vitamin K

vitamin K1

vitamin K1

Vitamin K1

maximum tolerated dose

toxicities

tumor marker responses

DCP levels

AFP levels .

PRs

stable tumors

tumor progression .

unresectable HCC

HCC

HCC

HCC


In vitro determination of the chromatic effect of a silver nanoparticles solution linked to the gantrez S-97 copolymer on tooth enamel . Silver nanoparticles ( NNPs ) , alone or in combination with the bioadhesive Gantrez S-97 , have demonstrated their efficacy against Streptococcus mutans ; however , it is not known if this combination changes the color of teeth . The aim of this work was to measure the color changes occurring after the use of a Gantrez-NNP combination on enamel tooth blocks . Two study groups were randomly formed : enamel blocks brushed with ( a ) the Gantrez-NNP combination and ( b ) conventional toothpaste , for 1 minute once daily for 4 weeks , then rinsed with distilled water and placed in thymol solution . Color changes in the enamel blocks were measured using a Minolta colorimeter CR300 . Analysis of mixed models was performed with R 2.10.1 at a 95 % confidence level , using the nonlinear mixed effects ( NLME ) package . The results showed that there were no color changes over time , only a high luminosity equal in both groups . Our study showed that the use of the Gantrez-NNP combination is safe with respect to dental esthetics in the control of S. mutans .

silver nanoparticles solution

gantrez S-97 copolymer

Silver nanoparticles ( NNPs )

Gantrez S-97

Gantrez-NNP combination

the Gantrez-NNP combination

conventional toothpaste

Gantrez-NNP combination

chromatic effect

color of teeth

color changes

Color changes in the enamel blocks

Minolta colorimeter CR300

no color changes over time

high luminosity equal

safe

tooth enamel .

enamel blocks

dental esthetics


Comparison of different approaches for assessment of HER2 expression on protein and mRNA level : prediction of chemotherapy response in the neoadjuvant GeparTrio trial ( NCT00544765 ) . Human epidermal growth factor receptor 2 ( HER2 ) testing is an essential part of pathological assessment in breast cancer patients , as HER2 provides not only prognostic but also predictive information on response to targeted therapy . So far , HER2 test accuracy of immunohistochemistry/in situ-hybridization techniques is still under debate , and more reliable and robust technologies are needed . To address this issue and to evaluate the predictive value of HER2 on chemotherapy , we investigated a cohort of 278 patients from the GeparTrio trial , a prospective neoadjuvant anthracycline/taxane-based multicenter study . In the GeparTrio trial , patients were not treated with any anti-HER2 therapy , as this was not standard therapy at this time . The HER2 status was analyzed by three different approaches : local and central evaluation using immunohistochemistry combined with in situ-hybridization as well as evaluation of HER2 mRNA expression using kinetic RT-PCR from formalin-fixed , paraffin-embedded ( FFPE ) tissue samples using a predefined cutoff . HER2 overexpression/amplification was observed in 37.3 % ( 91/244 ) and 17.9 % ( 41/229 ) of the informative samples in the local and central evaluations , respectively . Positive HER2 mRNA levels were found in 19.8 % ( 55/278 ) . We observed a highly significant correlation between central HER2 expression and HER2 status measured by kinetic RT-PCR ( r = 0.856 , P < 0.0001 ) and an overall agreement of 95.6 % ( κ statistic , 0.862 , CI 0.77-0.94 ) . Further , central HER2 as well as HER2 mRNA expression were predictors for a pathological complete response after neoadjuvant anthracycline/taxane-based primary chemotherapy in a univariate binary logistic regression analysis ( OR 3.29 , P = 0.002 ; OR 2.65 , P = 0.004 ) . The predictive value could be confirmed for the central HER2 status by multivariate analysis ( OR 3.04 , P = 0.027 ) . The locally assessed HER2 status was not predictive of response to chemotherapy . Our results suggest that standardized methods are preferable for evaluation of HER2 status . The kinetic RT-PCR from FFPE tissue might be an additional approach for assessment of this important prognostic and predictive parameter but has to be confirmed by other studies .

chemotherapy

chemotherapy

anti-HER2 therapy

immunohistochemistry

in situ-hybridization

kinetic RT-PCR

HER2 status

HER2 mRNA expression

HER2 overexpression/amplification

Positive HER2 mRNA levels

HER2 status measured by kinetic RT-PCR

breast cancer


Effect of weight loss on inflammation in patients with mild obstructive sleep apnea . BACKGROUND AND AIMS Inflammation may be one mediating mechanism for cardiovascular diseases in obstructive sleep apnea ( OSA ) . However , little is known about subclinical inflammation or the effect of lifestyle intervention on inflammation in early stages of OSA . The aim of this substudy of an existing randomized controlled trial , with post hoc analyses , was to determine the impact of lifestyle changes aimed at weight reduction on inflammatory biomarkers in overweight patients with mild OSA . METHODS AND RESULTS Patients were randomized to supervised intensive lifestyle intervention group ( N=28 ) or to control group ( N=31 ) , which received routine lifestyle advices . Circulating concentrations of pro- and anti-inflammatory mediators were measured before and after the 1-year intervention . The concentrations of two pro-inflammatory mediators , high-sensitivity C-reactive protein ( hsCRP ) and interleukin ( IL ) -6 , decreased significantly in both groups . Although the changes in inflammatory biomarkers favored the supervised lifestyle intervention , the only significant reduction observed between the groups was for the anti-inflammatory IL-1 receptor antagonist ( IL-1RA ) . The change in hsCRP was associated with apnea-hypopnea index , and improving night-time oxygen saturation was related to tumor necrosis factor alpha . IL-1RA and IL-6 were associated with insulin metabolism . CONCLUSION Weight loss resulted in reductions in concentrations of some pro- and anti-inflammatory mediators in overweight patients with mild OSA , overall favoring the supervised lifestyle intervention . These findings suggest that more intensive treatment of obesity in OSA patients might be well-justified .

control group

routine lifestyle advices

lifestyle intervention

lifestyle intervention

inflammatory biomarkers favored

change in hsCRP

apnea-hypopnea index

improving night-time oxygen saturation

Weight loss

cardiovascular diseases

obstructive sleep apnea ( OSA )

overweight

mild OSA .

overweight

mild OSA

OSA


Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis : the role of acute-phase reactants . OBJECTIVE To determine the effects of tocilizumab on rheumatoid arthritis ( RA ) disease activity and remission assessment , using measures that do or do not comprise acute-phase reactants . METHODS Simplified Disease Activity Index ( SDAI ) scores , Clinical Disease Activity Index ( CDAI ) scores , and the Disease Activity Score in 28 joints ( DAS28 ) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease-modifying antirheumatic drugs . The CDAI does not contain an acute-phase reactant component . Disease activity states , including remission , were defined using established cut points ; for the DAS28 , an alternative cut point of < 2.4 was also used . RESULTS Changes in the DAS28 , the SDAI score , and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo , and the magnitude of these changes was similar for the SDAI and the CDAI . Among patients who achieved 50 % improvement in disease activity according to the American College of Rheumatology criteria , only ∼20 % required a reduction in acute-phase reactant values in order to fulfill the criteria . However , DAS28 remission rates were higher ( even when using the lower cut point ) than the SDAI and CDAI remission rates . Only a minority of tocilizumab-treated patients with DAS28 remission also had disease remission according to the SDAI ( 26 % ) or CDAI ( ∼21 % ) . With infliximab treatment , SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment , and DAS28 remission rates were lower . Tocilizumab-treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates ( ESRs ) compared with patients with SDAI or CDAI remission . CONCLUSION Disease activity in RA is reduced by tocilizumab treatment , irrespective of the type of composite measure used to evaluate disease activity . Remission rates were much higher using the DAS28 compared with the SDAI and CDAI , due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR . Using the stringent SDAI and CDAI criteria , however , remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors .

tocilizumab

tocilizumab

tocilizumab

disease-modifying antirheumatic drugs

tocilizumab

placebo

disease activity

remission assessment

Changes in the DAS28

the SDAI score

CDAI score

SDAI

CDAI

improvement in disease activity


The nightly use of sodium oxybate is associated with a reduction in nocturnal sleep disruption : a double-blind , placebo-controlled study in patients with narcolepsy . OBJECTIVE To further explore the effects of sodium oxybate ( SXB ) administration on nocturnal sleep in narcolepsy patients during a double-blind , placebo-controlled , parallel group study conducted with 228 adult patients with narcolepsy/cataplexy in the United States , Canada , and Europe . METHOD Patients were withdrawn from antidepressants and sedative/hypnotics , and then randomized to receive 4.5 , 6 , or 9 g SXB or placebo nightly for 8 weeks . Patients receiving 6 and 9 g/night doses were titrated to their final dose in weekly 1.5 g increments , while patients receiving placebo were randomized to undergo a similar mock dose titration . The use of stimulant therapy continued unchanged . Changes in sleep architecture were measured using centrally scored nocturnal polysomnograms . Daily diaries were used to record changes in narcolepsy symptoms and adverse events . RESULTS Following 8 weeks of SXB treatment , study patients demonstrated significant dose-related increases in the duration of stage 3 and 4 sleep , reaching a median increase of 52.5 minutes in patients receiving 9 g nightly . Compared to placebo-treated patients , delta power was significantly increased in all dose groups . Stage 1 sleep and the frequency of nocturnal awakenings were each significantly decreased at the 6 and 9 g/night doses . The changes in nocturnal sleep coincided with significant decreases in the severity and frequency of narcolepsy symptoms . CONCLUSIONS The nightly administration of SXB to narcolepsy patients significantly impacts measures of slow wave sleep , wake after sleep onset , awakenings , total sleep time , and stage 1 sleep in a dose-related manner . The frequency and severity of narcolepsy symptoms decreased with treatment .

sodium oxybate

placebo-controlled

sodium oxybate ( SXB )

placebo

placebo

nocturnal sleep disruption

nocturnal sleep

Changes in sleep architecture

duration of stage 3 and 4 sleep

delta power

changes in nocturnal sleep

slow wave sleep

wake after sleep onset

awakenings

total sleep time

stage 1 sleep

nocturnal sleep disruption :

patients with narcolepsy .

narcolepsy patients


Controlled , prospective , randomized , clinical evaluation of partial ceramic crowns inserted with RelyX Unicem with or without selective enamel etching . 1-year results . PURPOSE To compare the performance of partial ceramic crowns ( PCCs ) inserted with RelyX Unicem ( RXU ) either with ( RXU+E ) or without ( RXU ) selective enamel etching . METHODS 34 patients ( 15 male , 19 female ) participated in the investigation , with a total of 68 PCC restorations . In each patient , one PCC was randomly assigned to insertion with RXU , the second PCC was assigned to insertion with RXU+E . The PCCs were CAD/CAM fabricated using the Cerec 3 system . RXU : 25 PCCs were placed in molars , nine in premolars . RXU+E : 26 PCCs were placed in molars , eight in premolars . The restorations were clinically rated using modified United States Public Health Service ( USPHS ) criteria at baseline , 6 and 12 months after placement . The median patient age was 41 years ( 24-59 years ) . The median ( 25-75 % ) PBI was 6 % ( 3-9 % ) . RESULTS All patients were available for the three recall appointments . One PCC ( RXU ) debonded after 11 months in situ , one PCC ( RXU+E ) fractured after 12 months in situ . Both restorations had to be replaced . At the 12 months recall , 66 of 68 controlled restorations were functional without need of replacement . The evaluation using USHPS criteria revealed a significant decrease of alfa ratings over time with respect to criteria marginal adaptation and marginal discoloration . No statistically significant differences between the two luting techniques , RXU and RXU+E , we reobserved during the observation period of 1 year . Within the limitations of the present study , adhesive luting with RXU with or without selective enamel etching can be recommended .

partial ceramic crowns

PCC

RXU

PCC

RXU+E

Cerec 3 system

RXU

RXU+E

RXU

RXU+E

RXU

RXU+E

RXU

partial ceramic crowns ( PCCs )

debonded

fractured

restorations

replaced

functional

alfa ratings over time


Impact of a fixed combination of clindamycin phosphate 1.2 % -benzoyl peroxide 2.5 % aqueous gel on health-related quality of life in moderate to severe acne vulgaris . The acne-specific quality of life ( Acne-QoL ) questionnaire was developed to measure the impact of facial acne across 4 domains ( acne symptoms , role-emotional , self-perception , role-social ) of health-related quality of life ( HRQL ) . This analysis assessed the impact of clindamycin phosphate 1.2 % -benzoyl peroxide 2.5 % ( clindamycin-BPO 2.5 % ) gel on HRQL in a combined study population ( N = 2813 ) of participants with moderate to severe acne vulgaris . Although the results presented within do not include factors of study and study-by-treatment interaction , analyses were performed to confirm that the results were consistent across the 2 identical , double-blind , randomized studies and within each treatment group across studies to justify pooling the data from both studies . The Acne-QoL questionnaire was administered at baseline and at the end of treatment ( week 12 ) . Treatment with clindamycin-BPO 2.5 % gel significantly improved participant-reported HRQL across all 4 domains compared with individual active ingredients and vehicle ( P < .001 ) . The percentage improvement in mean Acne-QoL domain scores with clindamycin-BPO 2.5 % gel ranged from 37 % to 59 % . Because the negative impact of facial acne on HRQL is one of the primary motivators for patients to seek treatment , this analysis underscores the importance of physicians incorporating assessments of HRQL into their clinical decision making .

clindamycin-BPO

clindamycin-BPO

Impact

measure the impact of facial acne

Acne-QoL questionnaire

HRQL

mean Acne-QoL domain scores

HRQL

moderate to severe acne vulgaris


Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer : a randomized phase II study . PURPOSE Increased growth factor signaling may contribute to tamoxifen resistance . This randomized phase II trial assessed tamoxifen plus placebo or the epidermal growth factor receptor inhibitor gefitinib in estrogen receptor ( ER ) -positive metastatic breast cancer . EXPERIMENTAL DESIGN Patients with newly metastatic disease or recurred after adjuvant tamoxifen ( stratum 1 ) , or recurred during/after adjuvant aromatase inhibitor ( AI ) or after failed first-line AI ( stratum 2 ) , were eligible . Primary variables were progression-free survival ( PFS ; stratum 1 ) and clinical benefit rate ( CBR ; stratum 2 ) . A 5 % or more improvement in response variables with gefitinib was considered to warrant further investigation . Outcome was correlated with biomarkers measured on the primary tumor . RESULTS In stratum 1 ( n = 206 ) , the PFS HR ( gefitinib : placebo ) was 0.84 ( 95 % CI , 0.59-1.18 ; median PFS 10.9 versus 8.8 months ) . In the stratum 1 endocrine therapy-naïve subset ( n = 158 ) the HR was 0.78 ( 95 % CI , 0.52-1.15 ) , and the prior endocrine-treated subgroup ( n = 48 ) 1.47 ( 95 % CI , 0.63-3.45 ) . In stratum 1 , CBRs were 50.5 % with gefitinib and 45.5 % with placebo . In stratum 2 ( n = 84 ) , CBRs were 29.2 % with gefitinib and 31.4 % with placebo . Biomarker analysis suggested that in stratum 1 there was greater benefit with gefitinib in patients who were ER-negative or had lower levels of ER protein . CONCLUSIONS In stratum 1 , the improved PFS with gefitinib plus tamoxifen met the protocol criteria to warrant further investigation of this strategy . In stratum 2 , there was a numerical disadvantage for gefitinib ; additional investigation after AI therapy is not warranted . Studies of predictive biomarkers are needed to subset appropriate patients .

Gefitinib

placebo

tamoxifen

placebo

tamoxifen

gefitinib

gefitinib : placebo

progression-free survival

clinical benefit rate

PFS HR

median PFS

metastatic breast cancer

metastatic disease


The dud effect : adding highly dissimilar fillers increases confidence in lineup identifications . Recent research in decision-making has demonstrated the " dud-alternative effect " -- the tendency to become more confident that a chosen response option is correct if it is surrounded by implausible response options ( Windschitl & Chambers , J Exp Psychol 30:198-215 , 2004 ) . This finding may be applicable to a lineup task : The presence of duds ( i.e. , highly dissimilar fillers ) may increase a witness 's confidence that an identified ( non-dud ) lineup member is the criminal . Four studies ( N = 665 ) demonstrate that the mere presence of highly dissimilar fillers inflates witnesses ' confidence in a mistaken identification ( Studies 1-4 ) , provides evidence that this confidence inflation is due to the duds inflating the perceived similarity of the other lineup members to the criminal ( Studies 2 , 3 ) , and delineates some conditions under which the effect holds ( Studies 3 , 4 ) . The addition of highly dissimilar lineup members , far from being inert , as is often implicitly assumed , can bias witnesses ' confidence reports .

dissimilar lineup members

witness 's confidence

witnesses ' confidence

confidence inflation


Efficient tetanus toxoid immunization on vitamin D supplementation . BACKGROUND/OBJECTIVES Vitamin D mediates immunomodulatory functions , and its deficiency has been associated with an increased prevalence of immunological diseases . The supplementation of vitamin D might be therapeutically beneficial , for example , in lupus erythematosus patients . However , its affect on established recall immune responses is undefined . SUBJECTS/METHODS In all , 32 individuals were randomized in a placebo controlled , double-blind setting , and received vitamin D ( daily 2000 IU ) for 10 weeks followed by tetanus toxoid ( TT ) booster immunization . RESULTS During vitamin D supplementation the median 25-hydroxyvitamin D serum concentration increased to 80.3 nM , which as expected decreased in the placebo group to 29.1 nM during the ultraviolet-deprived winter months . The TT-specific immunoglobulin G ( IgG ) boost efficiency was marginal higher in the vitamin D group ( P = 0.04 ) . The increase of the 25-hydroxyvitamin D levels correlated with the increase of TT-IgG serum concentrations . The induction of specific serum IgA and specific antibody secreting cells was comparable between both groups . Accordingly , the TT-specific and polyclonally triggered T-cell cytokine profiles were stable as well . CONCLUSIONS Vitamin D supplementation was successful and booster immunization induced efficiently specific antibodies titers .

tetanus toxoid immunization

vitamin D

vitamin D

placebo

vitamin D

vitamin D

25-hydroxyvitamin D levels

TT-IgG serum concentrations .

serum IgA

TT-specific

tetanus toxoid immunization

vitamin D supplementation


Treatment of acute otitis media in children under 2 years of age . BACKGROUND Recommendations vary regarding immediate antimicrobial treatment versus watchful waiting for children younger than 2 years of age with acute otitis media . METHODS We randomly assigned 291 children 6 to 23 months of age , with acute otitis media diagnosed with the use of stringent criteria , to receive amoxicillin-clavulanate or placebo for 10 days . We measured symptomatic response and rates of clinical failure . RESULTS Among the children who received amoxicillin-clavulanate , 35 % had initial resolution of symptoms by day 2 , 61 % by day 4 , and 80 % by day 7 ; among children who received placebo , 28 % had initial resolution of symptoms by day 2 , 54 % by day 4 , and 74 % by day 7 ( P=0.14 for the overall comparison ) . For sustained resolution of symptoms , the corresponding values were 20 % , 41 % , and 67 % with amoxicillin-clavulanate , as compared with 14 % , 36 % , and 53 % with placebo ( P=0.04 for the overall comparison ) . Mean symptom scores over the first 7 days were lower for the children treated with amoxicillin-clavulanate than for those who received placebo ( P=0.02 ) . The rate of clinical failure -- defined as the persistence of signs of acute infection on otoscopic examination -- was also lower among the children treated with amoxicillin-clavulanate than among those who received placebo : 4 % versus 23 % at or before the visit on day 4 or 5 ( P < 0.001 ) and 16 % versus 51 % at or before the visit on day 10 to 12 ( P < 0.001 ) . Mastoiditis developed in one child who received placebo . Diarrhea and diaper-area dermatitis were more common among children who received amoxicillin-clavulanate . There were no significant changes in either group in the rates of nasopharyngeal colonization with nonsusceptible Streptococcus pneumoniae . CONCLUSIONS Among children 6 to 23 months of age with acute otitis media , treatment with amoxicillin-clavulanate for 10 days tended to reduce the time to resolution of symptoms and reduced the overall symptom burden and the rate of persistent signs of acute infection on otoscopic examination . ( Funded by the National Institute of Allergy and Infectious Diseases ; ClinicalTrials.gov number , NCT00377260 . ) .

immediate antimicrobial treatment

watchful waiting

amoxicillin-clavulanate

placebo

amoxicillin-clavulanate

placebo

amoxicillin-clavulanate

placebo

amoxicillin-clavulanate

placebo

amoxicillin-clavulanate

placebo

placebo

amoxicillin-clavulanate

amoxicillin-clavulanate

symptomatic response

rates of clinical failure

initial resolution of symptoms

Mean symptom scores

rate of clinical failure -- defined

Mastoiditis

Diarrhea and diaper-area dermatitis

nasopharyngeal colonization


The effect of an early education program on adult health : the Carolina Abecedarian Project randomized controlled trial . OBJECTIVES We explored whether a successful randomized controlled trial of early education , the Carolina Abecedarian Project ( ABC ) , which enrolled infants from 1972 to 1977 at the Frank Porter Graham Child Development Institute in Chapel Hill , North Carolina , improved health outcomes and behaviors by 21 years of age . METHODS ABC randomized 111 infants to receive an intensive early education program or nutritional supplements and parental counseling alone ; participants have been followed to the present day . We examined the effect of ABC on health outcomes and behavioral risk factors when participants were aged 21 years , and then explored the mediators of this relationship . RESULTS Relative to the control group , the ABC treatment group was previously found to have improved cognition and educational attainment . We found that the intervention also improved heath ( P = .05 ) and health behaviors ( P = .03 ) when participants were aged 21 years . These improvements in behaviors were not mediated by IQ , math and reading scores at 15 years of age , educational attainment , or health insurance . CONCLUSIONS Effective early education programs may improve health and reduce risky health behaviors in adulthood .

early education program

early education

control group

ABC treatment

Effective early education programs

improved heath

health behaviors

IQ , math and reading scores

adult health :


Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 ( Kesho Bora study ) : a randomised controlled trial . BACKGROUND Breastfeeding is essential for child health and development in low-resource settings but carries a significant risk of transmission of HIV-1 , especially in late stages of maternal disease . We aimed to assess the efficacy and safety of triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis in pregnant women infected with HIV . METHODS Pregnant women with WHO stage 1 , 2 , or 3 HIV-1 infection who had CD4 cell counts of 200-500 cells per μL were enrolled at five study sites in Burkina Faso , Kenya , and South Africa to start study treatment at 28-36 weeks ' gestation . Women were randomly assigned ( 1:1 ) by a computer generated random sequence to either triple antiretroviral prophylaxis ( a combination of 300 mg zidovudine , 150 mg lamivudine , and 400 mg lopinavir plus 100 mg ritonavir twice daily until cessation of breastfeeding to a maximum of 6·5 months post partum ) or zidovudine and single-dose nevirapine ( 300 mg zidovudine twice daily until delivery and a dose of 600 mg zidovudine plus 200 mg nevirapine at the onset of labour and , after a protocol amendment in December , 2006 , 1 week post-partum zidovudine 300 mg twice daily and lamivudine 150 mg twice daily ) . All infants received a 0·6 mL dose of nevirapine at birth and , from December , 2006 , 4 mg/kg twice daily of zidovudine for 1 week after birth . Patients and investigators were not masked to treatment . The primary endpoints were HIV-free infant survival at 6 weeks and 12 months ; HIV-free survival at 12 months in infants who were ever breastfed ; AIDS-free survival in mothers at 18 months ; and serious adverse events in mothers and babies . Analysis was by intention to treat . This trial is registered with Current Controlled Trials , ISRCTN71468401 . FINDINGS From June , 2005 , to August , 2008 , 882 women were enrolled , 824 of whom were randomised and gave birth to 805 singleton or first , liveborn infants . The cumulative rate of HIV transmission at 6 weeks was 3·3 % ( 95 % CI 1·9-5·6 % ) in the triple antiretroviral group compared with 5·0 % ( 3·3-7·7 % ) in the zidovudine and single-dose nevirapine group , and at 12 months was 5·4 % ( 3·6-8·1 % ) in the triple antiretroviral group compared with 9·5 % ( 7·0-12·9 % ) in the zidovudine and single-dose nevirapine group ( p=0·029 ) . The cumulative rate of HIV transmission or death at 12 months was 10·2 % ( 95 % CI 7·6-13·6 % ) in the triple antiretroviral group compared with 16·0 % ( 12·7-20·0 % ) in the zidovudine and single-dose nevirapine group ( p=0·017 ) . In infants whose mothers declared they intended to breastfeed , the cumulative rate of HIV transmission at 12 months was 5·6 % ( 95 % CI 3·4-8·9 % ) in the triple antiretroviral group compared with 10·7 % ( 7·6-14·8 % ) in the zidovudine and single-dose nevirapine group ( p=0·02 ) . AIDS-free survival in mothers at 18 months will be reported in a different publication . The incidence of laboratory and clinical serious adverse events in both mothers and their babies was similar between groups . INTERPRETATION Triple antiretroviral prophylaxis during pregnancy and breastfeeding is safe and reduces the risk of HIV transmission to infants . Revised WHO guidelines now recommend antiretroviral prophylaxis ( either to the mother or to the baby ) during breastfeeding if the mother is not already receiving antiretroviral treatment for her own health . FUNDING Agence nationale de recherches sur le sida et les hépatites virales , Department for International Development , European and Developing Countries Clinical Trials Partnership , Thrasher Research Fund , Belgian Directorate General for International Cooperation , Centers for Disease Control and Prevention , Eunice Kennedy Shriver National Institute of Child Health and Human Development , and UNDP/UNFPA/World Bank/WHO Special Programme of Research , Development and Research Training in Human Reproduction .

Triple antiretroviral

zidovudine

nevirapine prophylaxis

efficacy

safety

pregnant women infected with HIV .


Clinical evaluation of Er , Cr : YSGG and GaAlAs laser therapy for treating dentine hypersensitivity : A randomized controlled clinical trial . OBJECTIVE The advent of dental lasers has raised another possible treatment option for dentine hypersensitivity ( DH ) and has become a research interest in the last decades . The aim of this randomized , controlled , double-blind , split mouth , clinical study was to evaluate and compare the desensitizing effects of erbium , chromium-doped : yttrium , scandium , gallium and garnet ( Er , Cr : YSGG ) to galium-aluminium-arsenide ( GaAlAs ) laser on DH . METHODS Fifty-one patients participated in this study for a total of 174 teeth . DH was assessed for all groups with a visual analog scale . For each patient , the teeth were randomized to three groups . In the diode laser group , sensitive teeth were irradiated with the GaAlAs laser at 8.5J/cm ( 2 ) energy density . In the Er , Cr : YSGG laser group , sensitive teeth were irradiated with Er , Cr : YSGG laser in the hard tissue mode using a none-contact probe at an energy level of 0.25W and repetition rate of 20Hz , 0 % water and 10 % air . In the control group no treatment was performed . Treatment time was 60s for GaAlAs laser and 30s for Er , Cr : YSGG laser . RESULTS When compared with the control group and baseline data , in both laser groups , laser irradiation provided a desensitizing effect immediately after treatment and this effect was maintained throughout the study ( p < 0.05 ) . No significant differences between Er , Cr : YSGG and GaAlAs laser groups were found at any follow-up examination ( p > 0.05 ) . CONCLUSION Based on these findings , it may be concluded that both Er , Cr : YSGG and GaAlAs lasers were effective in the treatment of DH following a single application .

Er , Cr : YSGG and GaAlAs laser therapy

irradiated with Er , Cr : YSGG laser

no treatment

Er , Cr : YSGG laser .

GaAlAs laser

Er , Cr : YSGG and GaAlAs lasers

dentine hypersensitivity :

dentine hypersensitivity ( DH )

evaluate and compare

visual analog scale .

desensitizing effect

effective

dentine hypersensitivity :

Fifty-one


Pars plana vitrectomy for diabetic macular edema . Internal limiting membrane delamination vs posterior hyaloid removal . A prospective randomized trial . BACKGROUND Diabetes mellitus , as well as subsequent ocular complications such as cystoid macular edema ( CME ) , are of fundametal socio-economic relevance . Therefore , we evaluated the influence of internal limiting membrane ( ILM ) removal on longterm morphological and functional outcome in patients with diabetes mellitus ( DM ) type 2 and chronic CME without evident vitreomacular traction . METHOD Forty eyes with attached posterior hyaloid were included in this prospective trial and randomized intraoperatively . Prior focal ( n = 31 ) or panretinal ( n = 25 ) laser coagulation was permitted . Group I ( n = 19 patients ) underwent surgical induction of posterior vitreous detachment ( PVD ) , group II ( n = 20 patients ) PVD and removal of the ILM . Eleven patients with detached posterior hyaloid ( group III ) were not randomized , and ILM removal was performed . One eye had to be excluded from further analysis . Examinations included ETDRS best-corrected visual acuity ( BCVA ) , fluorescein angiography ( FLA ) and OCT at baseline , 3 and 6 months postoperatively . Main outcome measure was BCVA at 6 months , secondary was foveal thickness . RESULTS Mean BCVA over 6 months remained unchanged in 85 % of patients of group II , and decreased in 53 % of patients of group I . Results were not statistically significant different [ group I : mean decrease log MAR 95 % CI ( 0.06 ; 0.32 ) , group II : ( -0.02 ; 0.11 ) ] . OCT revealed a significantly greater reduction of foveal thickness following PVD with ILM removal [ group I : mean change : 95 % CI ( -208.95 μm ; -78.05 μm ) , group II : ( -80.90 μm : +59.17 μm ) ] . CONCLUSION Vitrectomy , PVD with or without ILM removal does not improve vision in patients with DM type 2 and cystoid diabetic macular edema without evident vitreoretinal traction . ILM delamination shows improved morphological results , and appears to be beneficial in eyes with preexisting PVD .

Pars plana vitrectomy

Internal limiting membrane delamination

posterior hyaloid removal

6 months

thickness

diabetes mellitus

chronic CME

Forty


[ Intravesical electrostimulation and magnetophoresis in overactive bladder in females : efficacy of Amus-01-Intramag device with Intrastim attachment ] . High-frequency intravesical electroneurostimulation was made simultaneously with magnetophoresis of the mixture based on oxibutinin . Compared to effects of oral intake of oxibutinin , such method was two times more effective in relation to overactive bladder symptoms relief in shorter duration of the treatment and reduced side effects . Laser Doppler flowmetry discovered that the above combined treatment corrects microcirculation in bladder mucosa .

oxibutinin

overactive bladder symptoms relief

side effects

overactive bladder in females :


Impact of early parenteral nutrition completing enteral nutrition in adult critically ill patients ( EPaNIC trial ) : a study protocol and statistical analysis plan for a randomized controlled trial . BACKGROUND For critically ill patients treated in intensive care units ( ICU ) , two feeding strategies are currently being advocated , one by American/Canadian and the other by European expert guidelines . These guidelines differ particularly in the timing of initiating parenteral nutrition ( PN ) in patients for whom enteral nutrition ( EN ) does not reach caloric targets . METHODS/DESIGN The EPaNIC trial is an investigator-initiated , non-commercial , multi-center , randomized , controlled , clinical trial with a parallel group design . This study compares early ( European guideline ) versus late ( American/Canadian guideline ) initiation of PN when EN fails to reach a caloric target . In the early PN group , PN is initiated within 24-48 hours after ICU admission to complete early enteral nutrition ( EN ) up to a calculated nutritional target . In the late PN group , PN completing EN is initiated when the target is not reached on day 8 . In both groups , the same early EN protocol is applied . The study is designed to compare clinical outcome ( morbidity and mortality ) in the 2 study arms as well as to address several mechanistical questions . We here describe the EPaNIC study protocol and the statistical analysis plan for the primary report of the clinical results . DISCUSSION The study has been initiated as planned on august 01 2007 . One interim analysis advised continuation of the trial . The study will be completed in February 2011 . TRIAL REGISTRATION ClinicalTrials ( NCT ) : NCT00512122 .

initiation of PN when EN fails

EN

morbidity and mortality

adult critically ill patients


Dark-phase light contamination disrupts circadian rhythms in plasma measures of endocrine physiology and metabolism in rats . Dark-phase light contamination can significantly disrupt chronobiologic rhythms , thereby potentially altering the endocrine physiology and metabolism of experimental animals and influencing the outcome of scientific investigations . We sought to determine whether exposure to low-level light contamination during the dark phase influenced the normally entrained circadian rhythms of various substances in plasma . Male Sprague-Dawley rats ( n = 6 per group ) were housed in photobiologic light-exposure chambers configured to create 1 ) a 12:12-h light : dark cycle without dark-phase light contamination ( control condition ; 123 μW/cm ( 2 ) , lights on at 0600 ) , 2 ) experimental exposure to a low level of light during the 12-h dark phase ( with 0.02 , 0.05 , 0.06 , or 0.08 μW/cm ( 2 ) light at night ) , or 3 ) constant bright light ( 123 μW/cm ( 2 ) ) . Dietary and water intakes were recorded daily . After 2 wk , rats underwent 6 low-volume blood draws at 4-h intervals ( beginning at 0400 ) during both the light and dark phases . Circadian rhythms in dietary and water intake and levels of plasma total fatty acids and lipid fractions remained entrained during exposure to either control conditions or low-intensity light during the dark phase . However , these patterns were disrupted in rats exposed to constant bright light . Circadian patterns of plasma melatonin , glucose , lactic acid , and corticosterone were maintained in all rats except those exposed to constant bright light or the highest level of light during the dark phase . Therefore even minimal light contamination during the dark phase can disrupt normal circadian rhythms of endocrine metabolism and physiology and may alter the outcome of scientific investigations .

Dark-phase light contamination

photobiologic light-exposure chambers

plasma

physiology

metabolism

chronobiologic rhythms

endocrine physiology and metabolism

6 per group


Factors predictive of severe hypoglycemia in type 1 diabetes : analysis from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized control trial dataset . OBJECTIVE Identify factors predictive of severe hypoglycemia ( SH ) and assess the clinical utility of continuous glucose monitoring ( CGM ) to warn of impending SH . RESEARCH DESIGN AND METHODS In a multicenter randomized clinical trial , 436 children and adults with type 1 diabetes were randomized to a treatment group that used CGM ( N = 224 ) , or a control group that used standard home blood glucose monitoring ( N = 212 ) and completed 12 months of follow-up . After 6 months , the original control group initiated CGM while the treatment group continued use of CGM for 6 months . Baseline risk factors for SH were evaluated over 12 months of follow-up using proportional hazards regression . CGM-derived indices of hypoglycemia were used to predict episodes of SH over a 24-h time horizon . RESULTS The SH rate was 17.9 per 100 person-years , and a higher rate was associated with the occurrence of SH in the prior 6 months and female sex . SH frequency increased eightfold when 30 % of CGM values were ≤ 70 mg/dL on the prior day ( 4.5 vs. 0.5 % ; P < 0.001 ) , but the positive predictive value ( PPV ) was low ( < 5 % ) . Results were similar for hypoglycemic area under the curve and the low blood glucose index calculated by CGM . CONCLUSIONS SH in the 6 months prior to the study was the strongest predictor of SH during the study . CGM-measured hypoglycemia over a 24-h span is highly associated with SH the following day ( P < 0.001 ) , but the PPV is low .

continuous glucose monitoring ( CGM )

CGM

control

standard home blood glucose monitoring

CGM

CGM

severe hypoglycemia

severe hypoglycemia ( SH )

clinical utility

continuous glucose monitoring ( CGM )

CGM-derived indices of hypoglycemia

SH rate

SH

SH frequency

CGM values


Prevalence of metabolic syndrome in rural and urban Chinese population in Qingdao . AIMS To investigate the prevalence of metabolic syndrome and its components in both rural and urban Chinese population . SUBJECTS AND METHODS A population-based crosssectional survey was conducted in Qingdao , China in 2006 with 6100 Chinese aged 35-74 yr invited and 5355 who attended ; 3357 subjects , 1562 urban ( 46.5 % ) and 1795 rural residents ( 53.5 % ) met the inclusion criteria for the current data analysis . The metabolic syndrome definitions of National Cholesterol Education Program Adult Treatment Expert Panel III ( NCEPATPIII ) 2004 , NCEP 2005 and International Diabetes Federation ( IDF ) were used . RESULTS The age-standardized prevalences of metabolic syndrome were 16.2 % , 32.2 % , and 28.3 % in men and 26.8 % , 37.2 % , and 34.6 % in women , according to the definitions of the NCEP 2004 , NCEP 2005 , and IDF , respectively . Urban men have more risk factors and higher prevalence of the metabolic syndrome than rural men , but the differences in women were not that striking . Elevated blood pressure ( 62.6 % ) was , among risk factors , most common in the study population , followed by central obesity ( 53.4 % ) , and hyperglycemia ( 52.2 % ) defined using the NCEP 2005 criteria . CONCLUSIONS Metabolic disorders were common among adult Chinese in both rural and urban areas in Qingdao .

population-based crosssectional survey

Prevalence of metabolic syndrome

prevalence of metabolic syndrome

Elevated blood pressure

central obesity

hyperglycemia


Using baby books to increase new mothers ' safety practices . OBJECTIVE To determine whether educational baby books are an effective method for increasing low-income , first-time mothers ' safety practices during their child 's first 18 months . METHODS Primiparous women ( n = 167 ) were randomly assigned to 1 of 3 groups : an educational book group , a noneducational book group , or a no-book group . Home visits and interviews measured safety practices when women were in their third trimester of pregnancy ( baseline ) and when their children were 2 , 4 , 6 , 9 , 12 , and 18 months of age . RESULTS Women in the educational book group had fewer risks in their homes and exercised more safety practices than the no-book group ( - 20 % risk reduction ; effect size = -.30 ) . When the safety practices involved little time or expense ( eg , putting away sharp objects ) , the educational book group was significantly more likely to engage in these behaviors than the no-book group ( 40 % higher practices ; effect size = 0.19 ) or noneducational book group ( 27 % higher practices ; effect size = 0.13 ) . However , no differences were found between groups for behaviors that required high effort in time , money , or hassle ( eg , installing latches on cabinets ) . CONCLUSIONS Educational baby books appear to be an easy and low-cost way to increase the safety practices of new mothers , especially if the practices involve little to no time , money , or hassle .

educational baby books

educational book group

noneducational book group

no-book group

new mothers ' safety practices

safety practices

fewer risks in their homes

safety practices

practices

little time or expense

Primiparous

women


Initial clinical experience with implantation of left ventricular lead guided by Overlay Ref for the treatment of congestive heart failure . BACKGROUND Cardiac resynchronization therapy ( CRT ) improves clinical outcome in selected patients with advanced congestive heart failure . The Overlay Ref technique may facilitate the procedure for implanting left ventricular ( LV ) pacing leads to deliver CRT . AIM To assess the feasibility of deploying a LV pacing lead into a coronary sinus side branch guided by Overlay Ref . METHODS Data from 88 consecutive patients who met the CRT implantation criteria in our hospital between 28 November 2007 and 30 December 2009 were randomly assigned to two groups . Forty-four patients underwent CRT device implantation using Overlay Ref to guide target vein selection and advance a specifically designed pacing lead into the target vein ( Overlay Ref group ) ; 44 patients were conventionally implanted ( control group ) . RESULTS LV lead implantation was successful in all patients . Mean CRT total procedure times ( skin-to-skin ) were : Overlay Ref group , 80.7 ± 18.0 min ; control group , 98.5 ± 32.2 min ; p = 0.029 . Mean placement of LV pacing lead into target vein times were : Overlay Ref group , 16.2 ± 7.7 min ; control group , 36.4 ± 23.4 min ; p=0.004 . Mean total fluoroscopy times were : Overlay Ref group , 13.6 ± 4.3 min ; control group , 23.8 ± 15.7 min ; p=0.007 . Mean LV lead fluoroscopy times were : Overlay Ref group , 5.7 ± 2.9 min ; control group , 14.4 ± 4.6 min ; p=0.003 . No major complications occurred . CONCLUSIONS Overlay Ref facilitates location of and entry into the coronary sinus , and shortens the duration of LV pacing lead implantation into the target vein .

CRT .

Overlay Ref .

CRT

Overlay Ref

implanted ( control group

LV lead implantation

Overlay Ref

outcome

Mean total fluoroscopy times

Mean LV lead fluoroscopy


Serotonergic control of TSH and PRL secretion in obese men . To evaluate whether the inhibitory control of TSH and the stimulatory control of prolactin ( PRL ) secretion exerted by endogenous serotonin was altered in obesity , 22 obese men and 10 normal controls were tested with TRH ( 200 micrograms IV bolus ) in the presence ( experimental test ) and absence ( control test ) of the serotonergic agonist fenfluramine ( 60 mg PO 90 min before TRH ) . Control and experimental tests were also performed in seven male patients with subclinical hypothyroidism and were repeated in the same obese subjects after substantial weight loss . Basal TSH levels were similar in control and obese men . Normal TSH responses to TRH ( peak less than or equal to 14 mU/L ) were observed in all normal controls ( mean peak +/- SE 9.8 +/- 0.6 mU/L ) . In contrast , obese men were divided into two groups : nine in whom the TRH-induced TSH rise was higher than normal ( group I : mean peak = 16.5 +/- 0.5 mU/L ) and 13 in whom it was normal ( group II : mean peak = 10.6 +/- 0.7 mU/L ) . The hypothyroid men all had elevated basal and TRH-stimulated TSH levels . Basal PRL concentrations were similar in the normal controls and both groups of obese subjects . The PRL response to TRH was lower in both group I and group II obese men than in normal controls and was similar between group I and group II . ( ABSTRACT TRUNCATED AT 250 WORDS )

TRH

serotonergic agonist fenfluramine

TSH

PRL secretion

TSH

Basal TSH levels

Normal TSH responses

TRH-induced TSH rise

basal and TRH-stimulated TSH levels

Basal PRL concentrations

obese

men

obese

men

normal

seven

subclinical hypothyroidism

obese

obese

obese

hypothyroid

obese