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MS2_dynamic_1_shot_test

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MS2_dynamic_1_shot0

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: An anthroposophic lifestyle , which has been associated with reduced allergy risk in children , has several characteristics that could influence gut microbiota . This study aim ed to investigate the impact of anthroposophic lifestyle as well as specific early life exposures on the gut microbiota . In total , 665 stool sample s from 128 mother-infant pairs from the ALADDIN birth cohort study were included . Sample s collected from infants at ages 6 days , 3 weeks , 2 months and 6 months , and from their mothers before and after delivery , respectively , were analyzed using 454-pyrosequencing . Information regarding lifestyle exposures was collected prospect ively through interviews and question naires . Six-month-old infants in anthroposophic families had a significantly higher abundance of Bifidobacterium and lower abundances of Bacteroides and Veillonella . Caesarean section and breastfeeding had a significant impact on the microbiota : caesarean section was primarily associated with delayed colonization of Bifidobacterium and Bacteroides , whereas breastfed children had a higher relative abundance of Bifidobacterium and a lower abundance of Clostridiales . However , despite large differences in lifestyle exposures , we determined no significant differences in the gut microbiota between the anthroposophic and non-anthroposophic mothers or their infants ' before 6 months of age Background Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality . Underst and ing microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome . Methods Prospect i ve longitudinal study of premature infants . Stool sample s were obtained weekly . DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing , comparing subjects with and without sepsis . Results Six neonates were 24–27 weeks gestation at birth and had 18 sample s analysed . Two subjects had no sepsis during the study period , two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation . 324 350 sequences were obtained . The meconium was not sterile and had predominance of Lactobacillus , Staphylococcus and Enterobacteriales . Overall , infants who developed sepsis began life with low microbial diversity , and acquired a predominance of Staphylococcus , while healthy infants had more diversity and predominance of Clostridium , Klebsiella and Veillonella . Conclusions In very low birth weight infants , the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis . Empiric , prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis , but the predominant pathogen previously identified in the microbiome . Our data suggest that there may be a ‘ healthy microbiome ’ present in extremely premature neonates that may ameliorate risk of sepsis . More research is needed to determine whether altered antibiotics , probiotics or other novel therapies can re-establish a healthy microbiome in neonates Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG ( ATCC 53103 ) , reduces incidence of atopic eczema in at-risk children during the first 2 years of life ( infancy ) . We have therefore assessed persistence of the potential to prevent atopic eczema at 4 years . Atopic disease was diagnosed on the basis of a question naire and a clinical examination . 14 of 53 children receiving lactobacillus had developed atopic eczema , compared with 25 of 54 receiving placebo ( relative risk 0.57 , 95 % CI 0.33 - 0.97 ) . Skin prick test reactivity was the same in both groups : ten of 50 children previously given lactobacillus compared with nine of 50 given placebo tested positive . Our results suggest that the preventive effect of lactobacillus GG on atopic eczema extends beyond infancy Abstract Objective : To test the hypothesis that maternal complications significantly affect gut colonization patterns in very low birth weight infants . Methods : Forty-nine serial stool sample s were obtained weekly from nine extremely premature infants enrolled in a prospect i ve longitudinal study . Sequencing of the bacterial 16S rRNA gene from stool sample s was performed to approximate the intestinal microbiome . Linear mixed effects models were used to evaluate relationships between perinatal complications and intestinal microbiome development . Results : Subjects with prenatal exposure to a non-sterile intrauterine environment , i.e. prolonged preterm premature rupture of membranes ( PPPROM ) and chorioamnionitis exposure , were found to have a relatively higher abundance of potentially pathogenic bacteria in the stool across all time points compared to subjects without those exposures , irrespective of exposure to postnatal antibiotics . Compared with those delivered by Caesarean section , vaginally delivered subjects were found to have significantly lower diversity of stool microbiota across all time points , with lower abundance of many genera , most in the family Enterobacteriaceae . Conclusions : We identified persistently increased potential pathogen abundance in the developing stool microbiota of subjects exposed to a non-sterile uterine environment . Maternal complications appear to significantly influence the diversity and bacterial composition of the stool microbiota of premature infants , with findings persisting over time Background The ' hygiene hypothesis ' suggests that early exposure to microbes can be protective against atopic disease . The intestinal microbial flora could operate as an important postnatal regulator of the Th1/Th2 balance . The aim of the study was to investigate the association between early intestinal colonisation and the development of asthma in the first 3 years of life . Methods In a prospect OUTPUT: Overall , a greater relative abundance of Bacteroidaceae , Clostridiaceae , and Enterobacteriaceae and a lower relative abundance of Bifidobacteriaceae and Lactobacillaceae is associated with the development of allergic sensitization , eczema , or asthma . Reduced bacterial diversity can be associated with the development of allergic disease . The association between the composition of the intestinal microbiota and the development of allergic disease or asthma is less consistent in older children than in neonates , suggesting that early‐life microbial exposure plays a more important role . INPUT: ABSTRACT A healthy intestinal microbiota is considered to be important for priming of the infants ' mucosal and systemic immunity . Breast-fed infants typically have an intestinal microbiota dominated by different Bifidobacterium species . It has been described that allergic infants have different levels of specific Bifidobacterium species than healthy infants . For the accurate quantification of Bifidobacterium adolescentis , Bifidobacterium angulatum , Bifidobacterium bifidum , Bifidobacterium breve , Bifidobacterium catenulatum , Bifidobacterium dentium , Bifidobacterium infantis , and Bifidobacterium longum in fecal sample s , duplex 5′ nuclease assays were developed . The assays , targeting rRNA gene intergenic spacer regions , were vali date d and compared with conventional PCR and fluorescent in situ hybridization methods . The 5′ nuclease assays were subsequently used to determine the relative amounts of different Bifidobacterium species in fecal sample s from infants receiving a st and ard formula or a st and ard formula supplemented with galacto- and fructo-oligosaccharides ( OSF ) . A breast-fed group was studied in parallel as a reference . The results showed a significant increase in the total amount of fecal bifidobacteria ( 54.8 % ± 9.8 % to 73.4 % ± 4.0 % ) in infants receiving the prebiotic formula ( OSF ) , with a diversity of Bifidobacterium species similar to breast-fed infants . The intestinal microbiota of infants who received a st and ard formula seems to resemble a more adult-like distribution of bifidobacteria and contains relatively more B. catenulatum and B. adolescentis ( 2.71 % ± 1.92 % and 8.11 % ± 4.12 % , respectively , versus 0.15 % ± 0.11 % and 1.38 % ± 0.98 % for the OSF group ) . In conclusion , the specific prebiotic infant formula used induces a fecal microbiota that closely resembles the microbiota of breast-fed infants also at the level of the different Bifidobacterium species Preterm infants have an impaired gut barrier function . We aim ed to determine the effects of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ( short-chain galacto-oligosaccharides (SCGOS)/long-chain fructo-oligosaccharides ( LCFOS ) ) and acidic oligosaccharides ( AOS ) on intestinal permeability of preterm infants as measured by the sugar absorption test in the first week of life . Furthermore , we determined host- and treatment-related factors associated with intestinal permeability . In a r and omised controlled trial , preterm infants with a gestational age < 32 weeks and /or birth weight ( BW ) < 1500 g received enteral supplementation of SCGOS/LCFOS/AOS or placebo ( maltodextrin ) between days 3 and 30 of life . Intestinal permeability , reflected by the urinary lactulose/mannitol ( L/M ) ratio after oral ingestion of lactulose and mannitol , was assessed at three time points : before the start of the study ( t = 0 ) , at day 4 ( t = 1 ) and at day 7 ( t = 2 ) of life . Data were analysed by generalised estimating equations . In total , 113 infants were included . Baseline patient and nutritional characteristics were not different between the SCGOS/LCFOS/AOS ( n 55 ) and the placebo groups ( n 58 ) . SCGOS/LCFOS/AOS had no effect on the L/M ratio between t = 0 and t = 2 . In both the groups , the L/M ratio decreased from t = 0 to t = 2 ( P < 0·001 ) . Low BW increased the L/M ratio ( P = 0·002 ) . Exclusive breast milk feeding and mixed breast milk/formula feeding during the first week of life decreased the L/M ratio ( P < 0·001 and P < 0·05 , respectively ) . In conclusion , enteral supplementation of a prebiotic mixture does not enhance the postnatal decrease in intestinal permeability in preterm infants in the first week of life BACKGROUND Galactooligosaccharides ( GOS ) and long-chain fructooligosaccharides ( lcFOS ) proliferate bifidobacteria in infant gut microbiota . However , it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring . OBJECTIVES We aim ed to test how supplementation with GOS and lcFOS ( GOS/lcFOS ) in the last trimester of pregnancy affects maternal and neonatal gut microbiota . Variables of fetal immunity were assessed as a secondary outcome . DESIGN In a r and omized , double-blind , placebo-controlled pilot study , 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS ( at a ratio of 9:1 ) or maltodextrin ( placebo ) from week 25 of gestation until delivery . Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal ( days 5 , 20 , and approximately 182 ) stool sample s. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis . RESULTS The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group ( 21. OUTPUT:

Current evidence from systematic review and meta- analysis revealed that probiotics are the most promising intervention in reduction of the incidence of NEC in VLBW neonates . As per the evidence , prebiotics modulate the composition of human intestine microflora to the benefit of the host by suppression of colonization of harmful microorganism and /or the stimulation of bifidobacterial growth , decreased stool viscosity , reduced gastrointestinal transit time , and better feed tolerance .

MS2_dynamic_1_shot1

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: BACKGROUND No studies have examined whether increased consumption of oat cereal , rich in soluble fiber , favorably alters lipoprotein particle size and number . OBJECTIVE We examined the effects of large servings of either oat or wheat cereal on plasma lipids , lipoprotein subclasses , lipoprotein particle diameters , and LDL particle number . DESIGN Thirty-six overweight men aged 50 - 75 y were r and omly assigned to consume daily for 12 wk either oat or wheat cereal providing 14 g dietary fiber/d . Before and after the intervention , plasma lipid and lipoprotein subclasses were measured with proton nuclear magnetic resonance spectroscopy , and whole-body insulin sensitivity was estimated with the frequently sample d intravenous-glucose-tolerance test . RESULTS Time-by-treatment interactions ( P < 0.05 ) for LDL cholesterol ( oat : -2.5 % ; wheat : 8.0 % ) , small LDL cholesterol ( oat : -17.3 % ; wheat : 60.4 % ) , LDL particle number ( oat : -5.0 % ; wheat : 14.2 % ) , and LDL : HDL cholesterol ( oat : -6.3 % ; wheat : 14.2 % ) were observed . Time-by-treatment interactions were nearly significant for total cholesterol ( oat : -2.5 % ; wheat : 6.3 % ; P = 0.08 ) , triacylglycerol ( oat : -6.6 % ; wheat : 22.0 % ; P = 0.07 ) , and VLDL triacylglycerol ( oat : -7.6 % ; wheat : 2.7 % ; P = 0.08 ) . No significant time-by-treatment interactions were observed for HDL cholesterol , HDL-cholesterol subclasses , or LDL , HDL , and VLDL particle diameters . Insulin sensitivity did not change significantly with either intervention . CONCLUSIONS The oat compared with the wheat cereal produced lower concentrations of small , dense LDL cholesterol and LDL particle number without producing adverse changes in blood triacylglycerol or HDL-cholesterol concentrations . These beneficial alterations may contribute to the cardioprotective effect of oat fiber BACKGROUND The US Food and Drug Administration ( FDA ) approved health cl aims for 2 dietary fibers , beta-glucan ( 0.75 g/serving ) and psyllium ( 1.78 g/serving ) , on the assumption that 4 servings/d would reduce cardiovascular disease risk . OBJECTIVE We assessed the efficacy of this dose of fibers in reducing serum lipid risk factors for cardiovascular disease . DESIGN Sixty-eight hyperlipidemic adults consumed a test ( high-fiber ) and a control low-fat ( 25 % of energy ) , low-cholesterol ( < 150 mg/d ) diet for 1 mo each in a r and omized crossover study . The high-fiber diet included 4 servings/d of foods containing beta-glucan or psyllium that delivered 8 g/d more soluble fiber than did similar , unsupplemented foods in the control diet . Fasting blood sample s and blood pressure readings were obtained at baseline and weeks 2 and 4 , and the subjects ' weight was monitored weekly . RESULTS Compared with the control diet , the high-fiber diet reduced total cholesterol ( 2.1 + /- 0.7 % ; P = 0.003 ) , total : HDL cholesterol ( 2.9 + /- 0.8 % ; P = 0.001 ) , LDL : HDL cholesterol ( 2.4 + /- 1.0 % ; P = 0.015 ) , and apolipoprotein B : A-I ( 1.4 + /- 0.8 % ; P = 0.076 ) . Applying the Framingham cardiovascular disease risk equation to the data confirmed a reduction in risk of 4.2 + /- 1.4 % ( P = 0.003 ) . Small reductions in blood pressure were found after both diets . The subjects reported no significant differences in palatability or gastrointestinal symptoms between the diets . CONCLUSIONS The reduction in serum lipid risk factors for cardiovascular disease supports the FDA 's approval of a health cl aim for a dietary fiber intake of 4 servings/d . Although relatively small in terms of patient treatment , the reduction in cardiovascular disease risk is likely to be significant on a population basis BACKGROUND Dietary fiber intake remains low despite increasing evidence for its health benefits , including laxation . OBJECTIVE We aim ed to assess the effects of increasing fiber intake on bowel habits and gastrointestinal tolerance in healthy persons consuming a typical Canadian or US diet . DESIGN Under a r and omized crossover design , 23 free-living participants consumed a typical Canadian or US diet ( 35 % fat , 12 g fiber/d ) and received 25.0 - 28.7 g fiber/d from each of 5 breakfast cereals : All-Bran ( AB ) , Bran Buds with Corn ( BBC ) , Bran Buds with Psyllium ( BBP ) , BBC with viscous fiber blend ( VFB ) , or a low-fiber control for 3 wk , with each study arm separated by a washout of > /=1 wk . Seven-day stool collection s and a symptom diary were obtained during the last week of each study arm . RESULTS All study cereals induced significant ( P < 0.05 ) increases in fecal bulk from the control diet at 128 + /- 38 g to 199 + /- 5 OUTPUT: There was a wide variety of fibre sources used , with little similarity between groups in the choice of intervention . Adverse events , where reported , appeared to mostly reflect mild to moderate gastrointestinal side-effects and these were generally reported more in the fibre intervention groups than the control groups . The pooled analyses for CVD risk factors suggest reductions in total cholesterol and LDL cholesterol with increased fibre intake , and reductions in diastolic blood pressure . INPUT: The effects of the soluble fiber konjac glucomannan ( GM ) on serum cholesterol concentrations were investigated in 63 healthy men in a double-blind crossover , placebo-controlled study . After a 2-wk baseline period , the subjects were given 3.9 g GM or placebo daily for 4 wk . After a washout period of 2 wk , crossover took place , followed by another 4 wk of treatment . The subjects were encouraged not to change their ordinary diets or general lifestyle during the investigation . GM fibers reduced total cholesterol ( TC ) concentrations by 10 % ( P < 0.0001 ) , low-density-lipoprotein cholesterol ( LDL-C ) concentrations by 7.2 % ( P < 0.007 ) , triglycerides by 23 % ( P < 0.03 ) , and systolic blood pressure by 2.5 % ( P < 0.02 ) . High-density-lipoprotein cholesterol ( HDL-C ) and the ratio of LDL-C to HDL-C did not change significantly . No change in diastolic blood pressure or body weight was observed . No adverse effects were observed . The results of this study show that GM is an effective cholesterol-lowering dietary adjunct BACKGROUND Fiber supplements added to a caloric diet have additional effects on weight reduction in overweight subjects . The aim of this study was to compare the effect of various commercial fiber supplements ( glucomannan , guar gum and alginate ) on weight reduction in healthy overweight subjects . MATERIAL / METHODS One hundred and seventy six men and women were included to receive either active fiber substance or placebo in r and omized placebo-controlled studies . The fiber supplements consisted of the viscous fibers glucomannan ( Chrombalance ) , glucomannan and guar gum ( Appe-Trim ) and glucomannan , guar gum and alginat ( Glucosahl ) . RESULTS All fiber supplements plus a balanced 1200 kcal diet induced significantly weight reduction more than placebo and diet alone , during a five week observation period . However , there were no significant differences between the different fibers in their ability to induce weight reduction , which was approximately 0.8 kg/week ( 3.8 + /- 0.9 , 4.4 + /- 2.0 , 4.1 + /- 0.6 in the Chrombalance , Appe-Trim and Glucosahl group , respectively ) . CONCLUSIONS Glucomannan induced body weight reduction in healthy overweight subjects , whereas the addition of guar gum and alginate did not seem to cause additional loss of weight Dietary fibres are frequently used for the treatment of paediatric obesity . The aim of this clinical trial is to evaluate the efficacy of glucomannan in the child obesity management . This experimental design was double blinded with a block r and omisation , alpha = 0.05 , beta = 0.2 and delta = 50 % . The study involved 60 children under 15 years of age ( mean age 11.2 years , mean overweight 46 % ) , 30 of them under glucomannan treatment ( 1 g twice a day for two months ) and 30 under placebo and the same schedule . The drug and the placebo were indistinguishable both for the family and the physician . During the two months study period the children followed a normocaloric diet evaluated every two weeks by a dietetic record book . At the beginning of the study the drug and the placebo groups were comparable in regards to anthropometric data . At the end , the mean overweight of the drug group was decreased from 49.5 % to 41 % and that of the placebo group from 43.9 % to 41.7 % . Both decreases were significant ( p < 0.01 ) , but no significant difference was observed between the drug and the placebo groups . The only significant difference concerned the lipid metabolism . The children under glucomannan treatment manifested a significant decrease of alpha-lipoprotein and an increase of pre-beta-lipoprotein and triglycerides ; the children under placebo manifested only a decrease of triglycerides and apo beta-lipoprotein . We suggest that this metabolic alteration may derive from a primary decrease of alpha-lipoprotein , most likely because of an inadequate water intake . ( ABSTRACT TRUNCATED AT 250 WORDS Carbohydrate-restricted diets ( CRDs ) promote weight loss , reductions in plasma triacylglycerol ( TAG ) levels , and increases in high-density lipoprotein cholesterol ( HDL-C ) levels but may cause undesirable low-density lipoprotein cholesterol ( LDL-C ) responses in some people . The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease . Using a parallel-arm , double-blind , placebo-controlled design , 30 overweight and obese men ( body mass index , 25 - 35 kg/m(2 ) ) were r and omly assigned to supplement a CRD with soluble fiber ( Konjac-mannan , 3g/d ) ( n = 15 ) or placebo ( n = 15 ) . Plasma lipids , anthropometrics , body composition , blood pressure , and nutrient intake were evaluated at baseline and at 6 and 12 weeks . Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria . Both groups experienced decreases in ( P < .01 ) body weight , percent body fat , systolic blood pressure , waist circumference , and plasma glucose levels . After 12 weeks , HDL-C and TAG improved significantly in the fiber ( 10 % and -34 % ) and placebo ( 14 % , -43 OUTPUT:

The use of glucomannan did not appear to significantly alter any other study endpoints . Pediatric patients , patients receiving dietary modification , and patients with impaired glucose metabolism did not benefit from glucomannan to the same degree . Glucomannan appears to beneficially affect total cholesterol , LDL cholesterol , triglycerides , body weight , and FBG , but not HDL cholesterol or BP

MS2_dynamic_1_shot2

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: The current study was design ed to explore the use of behavioral ( i.e. , accuracy and reaction times ) and electrophysiological measures ( i.e. , event-related potentials ) to assess the impact of a family-based preventive intervention for preschool-aged , maltreated children in foster care . These measures were recorded during a computerized flanker task design ed to assess cognitive control and response monitoring . The sample was recruited from a larger r and omized efficacy trial of Multidimensional Treatment Foster Care for Preschoolers ( MTFC-P ) and included foster children assigned to the intervention condition ( n = 10 ) , foster children assigned to a services-as-usual comparison condition ( n = 13 ) , and low-income , nonmaltreated community children ( n = 11 ) . The children ’s behavioral and electrophysiological performance on the task was generally consistent with previous research with adults and older children . There were no group differences on the behavioral measures of cognitive control or response monitoring . Notably , however , group differences were observed on the electrophysiological measures of response monitoring . Specifically , the foster children who received services as usual were significantly less responsive to performance feedback about errors than the foster children who received the intervention and the nonmaltreated children . Applications of this methodology and implication s of the results for future prevention research are discussed Children with language processing deficits have various learning impairments and poor scholastic performance . In 3 - 10 % of all children a specific language processing deficit can be identified by the Sound Connecting Sub-Test of the Illinois Test of Psycholinguistic-Abilities ( SC-ITPA ) . These children among which we drew our index group ( AS-Group ) suffer from the disability to recognize isolated sounds as parts of words . Following linguistic terminology this is known as an auditory sequential sound processing deficit ( ASSPD ) Eighteen children ( AS-Group ) and 21 controls ( C-Group ) were subjected to mapped P300 evoked potential analyses of cortical response to acoustic stimulation in the oddball paradigm . The data presented here show that there exists significant relation between the P300 amplitude reduction and ASSPD . The P300 amplitude decrease measured in the AS-Group is due to a reduced information transmission in accordance with Johnson 's Triarchic Model of the P300 Amplitude . The cerebral structures involved in poor language processing are localized at the left temporo-parietal cortex . This supports the hypothesis that the underlying neuronal defect of ASSPD is localized in the language center and not in the auditory pathway . The P300 amplitude may serve as electrophysiological tool to identify ASSPD and to quantify the degree of improvement in the course of specific therapy The magnocellular deficit theory is one of the prominent hypotheses in dyslexia research . However , recent studies have produced conflicting results . Ten dyslexic children and 12 controls were examined with visual evoked potentials elicited by r and om dot kinematogram . The experiment comprises two sequences , one with r and omly moving dots ( control condition ) and a second sequence where a fraction of the dots were moved coherently at the left or right side ( depending on the level of coherence , 10 % , 20 % , and 40 % of the dots ) . R and omly moving dots elicited two components , a P100 and P200 , which were not different between the groups . Coherently moving dots elicited a late positivity between 300 and 800 ms , which was significantly attenuated in dyslexic children . The area of this component becomes larger at a higher level of coherence . This study supports the hypothesis of an impairment of a specific magnocellular function in dyslexia PURPOSE To verify the effectiveness of the Cognitive Auditory Evoked Potential-P300 ( CAEP-P300 ) for monitoring the therapeutical evolution of students with developmental dyslexia . METHODS Twenty students diagnosed with developmental dyslexia , of both genders , aged between 8 and 14 years , divided into two r and omized groups , one of them su bmi tted to a phonological remediation program associated with reading and writing ( GI ) , and the other one representing the control group ( GII ) , participated in the study . The groups were paired up , and the individuals were su bmi tted to two evaluations of the CAEP-P300 and the same interval was kept for both . Paired Student 's t-test , ANOVA test , and Pearson 's correlation coefficient were used , adopting 5 % significance level . RESULTS The statistical comparison of the pre and post evaluations of each group demonstrated difference in the Phonological Awareness Test ( p=0.000 ) and in the P300 latency ( p=0.005 ) only for GI . CONCLUSION CAEP-P300 use for monitoring the therapeutical evolution of children with developmental dyslexia is possible and represents a viable option for intervention programs PURPOSE To evaluate whether a hypothesis suggesting that apraxia of speech results from phonological overspecification could be relevant for childhood apraxia of speech ( CAS ) . METHOD High-density EEG was recorded from 5 children with CAS and 5 matched controls , ages 5 - 8 years , with and without CAS , as they listened to r and omized sequences of CV syllables in two oddball paradigms : phonemic ( /ba/ , /pa/ ) and allophonic ( /pa/ , /p(h)a/ ) . RESULTS In the phonemic contrast condition , mismatch negativity ( MMN ) responses to oddball sounds were observed for the typically developing ( comparison ) group but not the CAS group , although a component similar to an immature mismatch response was apparent . The allophonic contrast did not elicit MMN responses in the comparison group , but in the CAS group , an MMN-like response was observed . CONCLUSION The authors propose that these preliminary findings are consistent with a view of CAS as a disorder that not only affects motor planning but also has a phonological component OUTPUT: The present meta- analysis demonstrates that speech therapy does not influence the latency and amplitude results of the P300 evoked potential in children undergoing speech therapy intervention INPUT: The aims of this study were 1 ) to evaluate whether subjects suffering from acute mountain sickness ( AMS ) during exposure to high altitude have signs of autonomic dysfunction and 2 ) to verify whether autonomic variables at low altitude may identify subjects who are prone to develop AMS . Forty-one mountaineers were studied at 4,559-m altitude . AMS was diagnosed using the Lake Louise score , and autonomic cardiovascular function was explored using spectral analysis of R-R interval and blood pressure ( BP ) variability on 10-min resting recordings . Seventeen subjects ( 41 % ) had AMS . Subjects with AMS were older than those without AMS ( P < 0.01 ) . At high altitude , the low-frequency ( LF ) component of systolic BP variability ( LF(SBP ) ) was higher ( P = 0.02 ) and the LF component of R-R variability in normalized units ( LF(RR)NU ) was lower ( P = 0.001 ) in subjects with AMS . After 3 mo , 21 subjects ( 43 % with AMS ) repeated the evaluation at low altitude at rest and in response to a hypoxic gas mixture . LF(RR)NU was similar in the two groups at baseline and during hypoxia at low altitude but increased only in subjects without AMS at high altitude ( P < 0.001 ) and did not change between low and high altitude in subjects with AMS . Conversely , LF(SBP ) increased significantly during short-term hypoxia only in subjects with AMS , who also had higher resting BP ( P < 0.05 ) than those without AMS . Autonomic cardiovascular dysfunction accompanies AMS . Marked LF(SBP ) response to short-term hypoxia identifies AMS-prone subjects , supporting the potential role of an exaggerated individual chemoreflex vasoconstrictive response to hypoxia in the genesis of AMS OBJECTIVE : Although a history of previous acute mountain sickness ( AMS ) is commonly used for providing advice and recommending its prophylaxis during subsequent exposure , the intraindividual reproducibility of AMS during repeated high-altitude exposure has never been examined in a prospect i ve controlled study . METHODS : In 27 nonacclimatized children and 29 adults , AMS was assessed during the first 48 hours after rapid ascent to 3450 m on 2 consecutive occasions 9 to 12 months apart . RESULTS : During the first exposure , 18 adults ( 62 % ) and 6 children ( 22 % ) suffered from AMS ; during the second exposure , 14 adults ( 48 % ) and 4 children ( 15 % ) suffered from this problem ( adults versus children , P ≤ .01 ) . Most importantly , the intraindividual reproducibility of AMS was very different ( P < .001 ) between children and adults . None of the 6 children having suffered from AMS during the first exposure suffered from AMS during the second exposure , but 4 children with no AMS during the first exposure did experience this problem during the second exposure . In contrast , 14 of the 18 adults who suffered from AMS on the first occasion also presented with this problem during the second exposure , and no new case developed in those who had not experienced AMS on the first occasion . CONCLUSIONS : In adults , a history of AMS is highly predictable of the disease on subsequent exposure , whereas in children it has no predictive value . A history of AMS should not prompt practitioners to advise against reexposure to high altitude or to prescribe drugs for its prophylaxis in children Study Objective : Despite causing significant morbidity throughout the mountainous regions of the world , the pathophysiology of acute mountain sickness ( AMS ) remains poorly understood . This study aims to improve the underst and ing of altitude illness by determining if vascular endothelial growth factor ( VEGF ) plays a role in the development of AMS . The purpose of this study was to determine if elevated plasma VEGF correlates with increased symptoms of AMS at high altitude . Patients and Methods : This is a prospect i ve study of a cohort of healthy climbers on Denali ( Mount McKinley ) in Alaska at 14 , 200 feet . Baseline demographics , medications , rates of ascent , and AMS scores were recorded . Pulse oximetry measurements and venous blood sample s were obtained . Comparisons were made between mountaineers with and without AMS . Results : Seventy-two climbers were approached for participation in the study ; 21 ( 29 % ) refused . Of the 51 climbers participating in the study , 14 subjects ( 27.5 % ) had symptoms of AMS and 37 subjects ( 72.5 % ) were free of symptoms of AMS . Plasma VEGF levels were 79.14 pg/dl ( SD : 121.44 ) and 57.57pg/dl ( SD : 102.71 ) in the AMS and non-AMS groups , respectively . These results were nonsignificant . Similarly , comparison of sex , age , rate of ascent , pulse oximetry values , or history of altitude illness did not reveal significant differences between the AMS and non-AMS groups . Conclusion : This study does not provide evidence in support of the theory that plasma VEGF correlates with symptoms of AMS Forty-seven climbers participated in a double-blind , r and omized trial comparing acetazolamide 250 mg , dexamethasone 4 mg , and placebo every eight hours as prophylaxis for acute mountain sickness during rapid , active ascent of Mount Rainier ( elevation 4,392 m ) . Forty-two subjects ( 89.4 percent ) achieved the summit in an average of 34.5 hours after leaving sea level . At the summit or high point attained above base camp , the group taking dexamethasone reported less headache , tiredness , dizziness , OUTPUT:

Ensuring that the characteristics of the history and future ascents are similar may improve the clinical utility of AMS history

MS2_dynamic_1_shot3

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: BACKGROUND There are no controlled , prospect i ve studies comparing the 10-year outcomes of anterior cruciate ligament ( ACL ) reconstruction using patellar tendon ( PT ) and 4-str and hamstring tendon ( HT ) autografts . HYPOTHESIS Comparable results are possible with HT and PT autografts . STUDY DESIGN Cohort study ; Level of evidence , 2 . METHODS One hundred eighty ACL-deficient knees that met inclusion criteria underwent ACL reconstruction ( 90 HT autograft , 90 PT autograft ) by one surgeon and were treated with an accelerated rehabilitation program . All knees were observed in a prospect i ve fashion with subjective , objective , and radiographic evaluation at 2 , 5 , 7 , and 10-year intervals . RESULTS At 10 years , there were no differences in graft rupture rates ( 7/90 PT vs. 12/90 HT , P = .24 ) . There were 20 contralateral ACL ruptures in the PT group , compared with 9 in the HT group ( P = .02 ) . In all patients , graft rupture was associated with instrumented laxity > 2 mm at 2 years ( P = .001 ) . Normal or near-normal function of the knee was reported in 97 % of patients in both groups . In the PT group , harvest-site symptoms ( P = .001 ) and kneeling pain ( P = .01 ) were more common than in the HT group . More patients reported pain with strenuous activities in PT knees than in HT knees ( P = .05 ) . Radiographic osteoarthritis was more common in PT knees than the HT-reconstructed knees ( P = .04 ) . The difference , however , was composed of patients with mild osteoarthritis . Other predictors of radiographic osteoarthritis were < 90 % single-legged hop test at 1 year and the need for further knee surgery . An " ideal " outcome , defined as an overall International Knee Documentation Committee grade of A or B and a radiographic grade of A at 10 years after ACL reconstruction , was associated with <3 mm of instrumented laxity at 2 years , the absence of additional surgery in the knee , and HT grafts . CONCLUSIONS It is possible to obtain excellent results with both HT and PT autografts . We recommend HT reconstructions to our patients because of decreased harvest-site symptoms and radiographic osteoarthritis Purpose Primary aim of the study was analysis of hamstring tendon regeneration after anterior cruciate ligament reconstruction ( ACLR ) . Secondary aim was analysis of isokinetic muscle strength in relation to hamstring regeneration . The hypothesis was that regeneration of hamstring tendons after ACLR occurs and that regenerated hamstring tendons contribute to isokinetic hamstring strength with regeneration distal to the knee joint line . Methods Twenty-two patients scheduled for ACLR underwent prospect i ve MRI analysis of both legs . MRI parameters were tendon regeneration and morphology , muscle retraction and muscle cross-sectional area . A double-blind , prospect i ve analysis of isokinetic quadriceps and hamstrings strength was performed . Results Regeneration of the gracilis tendon after ACLR occurred in all patients . Regeneration of the semitendinosus tendon occurred in 14 patients . At 1 year , the surface area of the semitendinosus and gracilis muscle decreased compared to both preoperatively ( P < 0.01 ) and the contralateral leg ( P < 0.01 ) . The cross-sectional area of the semitendinosus muscle decreased in the absence of tendon regeneration ( P = 0.05 ) . The cross-sectional area of the gracilis muscle was greater in case of regeneration distal to the joint line ( P = 0.01 ) . Muscle retraction of the semitendinosus muscle was increased in case of nonregeneration ( P = 0.02 ) . There was no significant relationship between isokinetic flexion strength and tendon regeneration . Conclusion Hamstring tendons regenerated after harvest of both semitendinosus and gracilis tendons for ACLR . There was no relation between isokinetic flexion strength and tendon regeneration . Level of evidence Prognostic study , Level II Abstract Coactivation of knee flexors during knee extension assists in joint stability by exerting an opposing torque to the anterior tibial displacement induced by the quadriceps . This opposing torque is believed to be generated by eccentric muscle actions that stiffen the knee , thereby attenuating strain to joint ligaments , particularly the anterior cruciate ligament ( ACL ) . However , as the lengths of knee muscles vary with changes in joint position , the magnitude of flexor/extensor muscle force coupling may likewise vary , possibly affecting the capacity for active knee stabilization . The purpose of this study was to assess the effect of changes in movement speed and joint position on eccentric/concentric muscle action relationships in the knees of uninjured ( UNI ) and post-ACL-surgery ( INJ ) subjects ( n = 14 ) . All subjects were tested for maximum eccentric and concentric torque of the contralateral knee flexors and extensor muscles at four isokinetic speeds ( 15 ° –60 ° · s−1 ) and four joint position intervals ( 20 ° –60 ° of knee flexion ) . Eccentric flexor torque was normalized to the percentage of concentric flexor torque generated at each joint position interval for each speed tested ( flexor E-C ratio ) . In order to estimate the capacity of the knee flexors to resist active knee extension , the eccentric-flexor/concentric-extensor ratios were also computed for each joint position interval and speed ( flexor/extensor E-C ratio ) . The results revealed that eccentric torque surpassed concentric torque by 3%–144 % across movement speeds and joint position OUTPUT: Some of these deficits persisted up to 5 years after surgery . Knee flexor strength is more impaired after ACL reconstruction with hamstring grafts and quadriceps strength after BPTB ACL reconstruction . ConclusionS trength deficits of hip , knee and ankle muscles are reported after ACL reconstruction . Muscular strength test may be an important tool to determine if an athlete can return to competitive sports after ACL reconstruction INPUT: Abstract . This study documented postoperative morbidity during the first 4 months following anterior cruciate ligament ( ACL ) reconstruction using either patellar tendon or hamstring tendon autograft . Sixty-five patients undergoing primary arthroscopically assisted single-incision ACL reconstruction were r and omized to have a central third bone patellar tendon bone autograft ( PT ) or a doubled semitendinosus/doubled gracilis autograft ( HS ) . Postoperatively patients undertook a st and ard ' accelerated ' rehabilitation protocol . Patients were review ed after 2 weeks , 8 weeks , and 4 months . At each review the location and severity of general knee pain and the presence and severity of anterior knee pain ( AKP ) were recorded as were the presence and size of an effusion as well as the active and passive flexion and passive extension deficits compared to the contralateral limb . Pain on kneeling , KT-1000 measured side to side difference in anterior tibial displacement , isokinetic assessment of quadriceps and hamstring peak torque deficits , IKDC score and Cincinnati sports activity level were also recorded after 4 months . After 2 weeks more patients in the PT group complained of AKP and reported that the pain was more severe . After 8 weeks there was no significant difference between the groups for any variable . After 4 months the severity of general pain experienced and the incidence of pain on kneeling were greater in the PT group . The PT group also demonstrated a significantly greater quadriceps peak torque deficit at 240 ° /s . IKDC scores were higher in the HS group , but Cincinnati sports activity scores were higher in the PT group . Although we observed a lower morbidity in the HS group , primarily related to pain , the severity of pain in both groups was relatively low and , in light of the higher mean sports activity level observed in the PT group at 4 months the clinical impact of the difference may not be significant BACKGROUND There are no controlled , prospect i ve studies comparing the 10-year outcomes of anterior cruciate ligament ( ACL ) reconstruction using patellar tendon ( PT ) and 4-str and hamstring tendon ( HT ) autografts . HYPOTHESIS Comparable results are possible with HT and PT autografts . STUDY DESIGN Cohort study ; Level of evidence , 2 . METHODS One hundred eighty ACL-deficient knees that met inclusion criteria underwent ACL reconstruction ( 90 HT autograft , 90 PT autograft ) by one surgeon and were treated with an accelerated rehabilitation program . All knees were observed in a prospect i ve fashion with subjective , objective , and radiographic evaluation at 2 , 5 , 7 , and 10-year intervals . RESULTS At 10 years , there were no differences in graft rupture rates ( 7/90 PT vs. 12/90 HT , P = .24 ) . There were 20 contralateral ACL ruptures in the PT group , compared with 9 in the HT group ( P = .02 ) . In all patients , graft rupture was associated with instrumented laxity > 2 mm at 2 years ( P = .001 ) . Normal or near-normal function of the knee was reported in 97 % of patients in both groups . In the PT group , harvest-site symptoms ( P = .001 ) and kneeling pain ( P = .01 ) were more common than in the HT group . More patients reported pain with strenuous activities in PT knees than in HT knees ( P = .05 ) . Radiographic osteoarthritis was more common in PT knees than the HT-reconstructed knees ( P = .04 ) . The difference , however , was composed of patients with mild osteoarthritis . Other predictors of radiographic osteoarthritis were < 90 % single-legged hop test at 1 year and the need for further knee surgery . An " ideal " outcome , defined as an overall International Knee Documentation Committee grade of A or B and a radiographic grade of A at 10 years after ACL reconstruction , was associated with <3 mm of instrumented laxity at 2 years , the absence of additional surgery in the knee , and HT grafts . CONCLUSIONS It is possible to obtain excellent results with both HT and PT autografts . We recommend HT reconstructions to our patients because of decreased harvest-site symptoms and radiographic osteoarthritis Two commercially available knee ligament arthrometers ( KT-1000 MEDmetric Corporation , San Diego , California and Kneelax MR Systems , Haarlem , The Netherl and s ) were used to measure anterior tibial translation . In this study 91 subjects with no history of knee pathology were tested using both devices . Both normal knees were tested and comparison of recorded anterior translation ( millimeters ) was performed . Absolute numbers at forces of 67N , 89N , 134N , and manual maximum displacements were recorded . Side-to-side differences were calculated and data were compared . There was a significant difference found between the absolute values of each device . The KT-1000 was found to record greater values in millimeters of translation . Although the absolute values were significantly different , the side-to-side differences were not significantly different between devices Background : Numerous studies have compared patellar tendon ( PT ) and hamstring tendon ( HS ) anterior cruciate ligament ( ACL ) reconstructions in the short to midterm , but fewer long-term results have been published . Hypothesis : There will be no difference in functional outcome between ACL reconstruction performed with PT and HS grafts , but PT grafts will have more donor site morbidity . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Sixty-five patients undergoing ACL reconstruction were r and omized to receive either a PT graft or a 4-str and HS graft . Early results were reported at 4 , 8 , 12 , 24 , and 36 months . Forty OUTPUT:

The QT autograft detected comparable rate of Lachman test > 3 mm , Pivot shift test > 3 m and instrumental laxity > 3 mm . The QT autograft showed a lower rate of autograft failure above all . The QT autograft detected the reduced rate of AKP than the PT . Quadriceps tendon autograft may represent a feasible option for primary ACL reconstruction .

MS2_dynamic_1_shot4

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: This study evaluated the efficacy , tolerability , and safety of darifenacin , an M3 selective receptor antagonist ( M3 SRA ) , in patients with overactive bladder ( OAB ) . In a multicenter , double-blind , placebo-controlled dose-ranging study , 439 adult OAB patients ( 85.4 % female ) were r and omized to darifenacin controlled-release tablets 7.5 mg ( n = 108 ) , 15 mg ( n = 107 ) or 30 mg ( n = 115 ) qd , or placebo ( n = 109 ) for 12 weeks . Darifenacin significantly reduced the median number of incontinence episodes/week ( −68.7 , −76.5 , and −77.3 % from baseline at 7.5 , 15 , and 30 mg , respectively , vs −46 % with placebo , all p < 0.01 ) and dose relatedly improved micturition frequency , frequency and severity of urgency , nocturia , and bladder capacity . Darifenacin was well tolerated . Adverse events were commonly mild to moderate dry mouth and constipation . There were no safety concerns . Darifenacin is effective and well tolerated in the treatment of OAB , with 7.5 and 15 mg doses offering flexibility of dosing for optimal treatment outcome Overactive bladder ( OAB ) has a significant impact on a patient ’s health-related quality of life ( HRQoL ) . This study assessed the HRQoL of Japanese OAB patients following 12 weeks ’ treatment with tolterodine extended release ( ER ) or oxybutynin . A total of 293 patients with symptoms of OAB were r and omized for treatment with tolterodine ER 4 mg once daily ( n=114 ) , oxybutynin 3 mg three times daily ( n=122 ) or a placebo ( n=57 ) . Treatment efficacy and safety assessment s were made over the 12-week period . HRQoL was assessed using the King ’s Health Question naire ( KHQ ) . Patients receiving tolterodine ER or oxybutynin showed a significant ( P<0.05 ) improvement in the Incontinence Impact , Role Limitations and most other KHQ domains compared with the placebo . These changes in HRQoL corresponded with significant ( P<0.05 ) improvements in micturition diary variables for patients receiving tolterodine ER and oxybutynin compared with placebo . Our findings demonstrate that Japanese OAB patients receiving tolterodine ER or oxybutynin experienced overall improvement in their quality of life The embarrassment and social stigma associated with urinary incontinence ( UI ) in overactive bladder syndrome ( OAB ) sufferers is a major reason for individuals to seek help for their condition . An analysis of 1,873 subjects with OAB with UI was conducted to assess the efficacy of solifenacin in reducing incontinence in a pooled population from four phase III clinical trials , stratified by severity of incontinence , urgency , and other key factors at baseline . Subjects were r and omized to either 5 or 10 mg of solifenacin once daily or placebo for 12 weeks . More than 50 % of the total population became continent at study end , with either dose of solifenacin ( P<0.01 vs placebo ) . Significant reductions in incontinence episodes and higher rates of attainment of continence vs placebo were observed irrespective of age or severity of incontinence or urgency at baseline with solifenacin treatment . Treatment was well tolerated , with the majority of adverse events being mild in nature . Solifenacin is an effective antimuscarinic agent for the treatment of incontinence associated with OAB PURPOSE In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder . In addition , we assessed the safety and acceptability of solifenacin . MATERIAL S AND METHODS The study was a multicenter , multinational , r and omized , double-blind , placebo controlled trial . Patients were r and omized to 12-week once daily treatment with solifenacin 5 mg , solifenacin 10 mg or placebo . The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours . Secondary efficacy variables included changes from baseline in mean number of urgency , nocturia and incontinence episodes per 24 hours , and mean volume voided per micturition . RESULTS Compared with changes obtained with placebo ( -1.59 ) , micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg ( -2.37 , p = 0.0018 ) and solifenacin 10 mg ( -2.81 , p = 0.0001 ) . A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses ( 5 mg , p = 0.002 and 10 mg , p = 0.016 ) . This effect was also seen for episodes of urge incontinence ( 5 mg , p = 0.014 and 10 mg , p = 0.042 ) . Of patients reporting incontinence at baseline , fully 50 % achieved continence after treatment with solifenacin . Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg ( -0.71 , -38.5 % ) versus placebo ( -0.52 , -16.4 % , p = 0.036 ) . Episodes of urgency were statistically significantly reduced with solifenacin 5 mg ( -2.84 , -51 % , p = 0.003 ) and solifenacin OUTPUT: Tolterodine immediate release ( IR ) had a more favorable profile of adverse events than oxybutynin IR . Regarding different dosages of IR formulations , dose escalation might yield some limited improvements in the efficacy but at the cost of significant increase in the rate of adverse events . In the comparisons between IR and extended-release ( ER ) formulations , the latter showed some advantages , both in terms of efficacy and safety . With regard to the route of administration , use if a transdermal route of administration does not provide significant advantage over an oral one . With regard to IR formulations , dose escalation might yield some improvements in the efficacy with significant increase in the AE . INPUT: OBJECTIVES To investigate the effects of darifenacin controlled-release ( CR ) and oxybutynin extended-release ( ER ) on cognitive function ( particularly memory ) in older subjects . METHODS Healthy subjects ( n=150 ) > /=60 years were r and omised to darifenacin , oxybutynin ER or placebo in a multicentre , double-blind , double-dummy , parallel-group , 3-week study . Doses were administered according to US labels : oxybutynin ER 10 mg once daily ( od ) , increasing to 15 mg od then 20 mg od by week 3 ; darifenacin 7.5 mg od in weeks 1 and 2 , then 15 mg od in week 3 . The primary end point was accuracy on the Name-Face Association Test ( delayed recall ) at week 3 . RESULTS Results of the Name-Face Association Test at week 3 showed no significant difference between darifenacin and placebo on delayed recall ( mean difference , -0.06 , p=0.908 ) . In contrast , oxybutynin ER result ed in memory impairment , with significantly lower scores than placebo and darifenacin ( mean differences , -1.30 , p=0.011 and -1.24 , p=0.022 , respectively ) for delayed recall on the Name-Face Association Test at week 3 . Additional tests of delayed recall indicated significant memory impairment with oxybutynin ER versus placebo at certain time points , whereas darifenacin was similar to placebo . No between-treatment differences were detected in self-rated memory , demonstrating that subjects were unaware of memory deterioration . CONCLUSIONS While darifenacin had no significant effects on memory versus placebo , oxybutynin ER caused significant memory deterioration ( magnitude of effect comparable to brain aging of 10 years ) . The results also demonstrate that subjects may not recognise/report memory deterioration INTRODUCTION Anti-cholinergic medications have been associated with increased risks of cognitive impairment , premature mortality and increased risk of hospitalisation . Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer , yet little is known about associated adverse outcomes in this setting . METHODS A sub study of 112 participants in a r and omised control trial who had cancer and an Australia modified Karnofsky Performance Scale ( AKPS ) score ( AKPS ) of 60 or above , explored survival and health service utilisation ; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale ( modified version ) longitudinally to death . A st and ardised starting point for prospect ively calculating survival was an AKPS of 60 or above . RESULTS Baseline entry to the sub- study was a mean 62 + /- 81 days ( median 37 , range 1 - 588 ) days before death ( survival ) , with mean of 4.8 ( median 3 , SD 4.18 , range 1 - 24 ) study assessment s in this time period . Participants spent 22 % of time as an inpatient . There was no significant association between anti-cholinergic score and time spent as an inpatient ( adjusted for survival time ) ( p = 0.94 ) ; or survival time . DISCUSSION No association between anti-cholinergic load and survival or time spent as an inpatient was seen . Future studies need to include cognitively impaired population s where the risks of symptomatic deterioration may be more substantial BACKGROUND Observational studies report a relationship between anticholinergic drug scale ( ADS ) score and cognitive function . This study investigated whether a reduced ADS score improved cognitive function in a frail elderly population . METHODS This r and omized , controlled , single-blinded trial , recruited long-term residents with an ADS score of greater than or equal to 3 from 22 nursing homes in Norway . The participants were r and omly allocated ( 1:1 ) to intervention or control . The intervention was a pharmacist-initiated reduction of ADS score after multidisciplinary drug review s. Primary end point was Consortium to Establish a Registry for Alzheimer 's Disease 10-wordlist test for immediate recall . Secondary end points were Mini-Mental Sate Examination , delayed recall and recognition of words , saliva flow , and serum anticholinergic activity (SAA).The participants were retested after 4 and 8 weeks , and the study groups were compared after adjusting for baseline differences . RESULTS Eighty-seven patients were included . The median ADS score was reduced by 2 units ( p < .0001 ) in the intervention group and remained unchanged in the control group . After 8 weeks , the adjusted mean difference in immediate recall was 0.54 words between the intervention and control group ( 95 % confidence interval [ CI ] : -0.91 , 2.05 ; p = .48 ) . The study groups did not differ significantly in any of the other cognitive end points , salvia flow , or SAA at either follow-up ( p > .18 ) . CONCLUSION Pharmacist-initiated drug changes significantly reduced ADS score but did not improve cognitive function in nursing home residents . Moreover , the drug changes did not reduce SAA or mouth dryness significantly , which might indicate limited applicability of the ADS score to prevent prescription risks in this population PURPOSE Overactive bladder is common in the elderly population , which is susceptible to cognitive disorders and drug induced cognitive impairment . Existing overactive bladder treatments may cause adverse events , such as cognitive impairment , due to antagonism of the M1 receptor in the central nervous system . In this study we evaluated the effect of darifenacin , an M3 selective antagonist , on cognitive function in elderly volunteers without clinical dementia . MATERIAL S AND METHODS This double-blind , 3-period crossover study r and omized 12 OUTPUT:

medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function , but limited evidence exists for delirium or mortality outcomes

MS2_dynamic_1_shot5

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: Abstract . Glucocorticoid-induced osteoporosis has been reported to be caused by enhanced bone resorption and suppressed bone formation . To clarify whether administration of vitamin K , which enhances bone formation , prevents prednisolone-induced loss of bone mineral density ( BMD ) , a r and omized , prospect i ve , controlled study was conducted on 20 patients with chronic glomerulonephritis scheduled for treatment with prednisolone . All patients were initially treated with 0.8 mg/kg body weight/day of prednisolone ( maximum of 40 mg ) for 4 weeks , tapering to 20 mg/day over approximately 6 weeks . Ten patients received prednisolone alone ( Group 1 ) , and the other 10 patients received prednisolone plus 15 mg of menatetrenone , vitamin K , three times per day ( Group 2 ) . BMD of the lumbar spine measured by dual-energy X-ray absorptiometry ( DXA ) and biochemical markers of bone metabolism in blood and urine were evaluated before and 10 weeks after administration of prednisolone alone or with menatetrenone . In Group 1 , treatment with prednisolone significantly reduced BMD of the lumbar spine from 1.14 ± 0.12 to 1.10 ± 0.11 g/cm2 ( P= 0.0029 ) . Serum intact osteocalcin and procollagen type I C-peptide ( PICP ) concentrations , biochemical markers of bone formation , were markedly reduced . A biochemical marker of bone resorption , urinary excretion of deoxypyridinoline , was significantly reduced . In Group 2 , prednisolone-induced reduction of BMD was prevented by menatetrenone administration ( 1.09 ± 0.09 to 1.07 ± 0.07 g/cm2 , P= 0.153 ) . Menatetrenone prevented reduction of PICP concentration by prednisolone but not in serum intact osteocalcin concentration and urinary excretion of deoxypyridinoline . Thus , treatment with prednisolone result ed in loss of BMD of the lumbar spine associated with suppression of both bone formation and bone resorption . Menatetrenone is a useful agent in preventing prednisolone-induced loss of BMD We have recently demonstrated that glucocorticoid ( GC ) suppresses bone formation and enhances bone resorption , with result ant bone loss . This altered bone turnover is not due to the action of parathyroid hormone ( PTH ) , but appears to be related to the suppression of osteoprotegerin ( OPG ) . As vitamin K2 ( menatetrenone ) has been used for the treatment of osteoporosis , the present study was carried out to evaluate the effect of vitamin K2 on GC-induced bone loss . Twenty patients with chronic glomerulonephritis treated with GC for the first time were chosen for this study . Ten patients received GC alone ( group A ) and the other 10 patients each received 15 mg of vitamin K2 per day in addition to GC ( group B ) . Markers of bone metabolism , including serum OPG , osteocalcin ( OC ) , bone-specific alkaline phosphatase activity ( BAP ) , PTH , tartrate-resistant acid phosphatase ( TRAP ) , and bone mineral density ( BMD ) , were measured before and during the treatment . OPG was significantly decreased in group A ( P < 0.001 ) , while no significant change was seen in group B. TRAP was markedly increased in both groups , more particularly in group A ( P < 0.01 ) . PTH was decreased in group A , but was increased in group B. OC was decreased at month 1 but subsequently increased until month 12 in both groups . BAP had decreased at month 3 in group A ( P < 0.05 ) , but not in group B. BMD of the lumbar spine was significantly reduced after 6 months ( P < 0.01 ) , and 12 months ( P < 0.001 ) of treatment in group A , whereas there was no remarkable change in group B. The present study demonstrated that the inhibition exerted by vitamin K2 of the reduction in OPG induced by GC may , at least in part , play a role in the prevention and treatment of GC-induced bone loss The purpose of this study was to evaluate the influence of gamma-glutamyl transferase ( GGCX ) gene polymorphisms on the response of serum undercarboxylated osteocalcin ( ucOC ) and bone turnover markers 3 months after treatment with menatetrenone . One hundred and forty postmenopausal Thai women were enrolled and assigned to receive 45 mg/day treatment of menatetrenone ( MK-4 ) concurrently with calcium 1.2 g and vitamin D 400 IU for 3 months . Demographic characteristics , GGCX genotyping , serum bone turnover markers and ucOC levels were obtained from all participants at baseline . We evaluated the reduction of ucOC at 3 months and the reduction of beta-CTx and P1NP at 1 and 3 months . The responses were compared between the different genotypes of GG and GA + AA groups . There was a significant reduction of serum ucOC , beta-CTx and P1NP from the baseline at 3 months ( p < 0.001 ) though there was no significant difference between genotypes ( GG vs. GA + AA ; p > 0.05 ) . Nonetheless , a subgroup analysis of postmenopausal women who 65 years of age or over ( N = 37 ) revealed a significant difference between the two groups in the reduction of ucOC . Menatetrenone significantly reduced serum ucOC as well as beta-CTX and P1NP from the baseline . GGCX polymorphism appeared to have an influence over the reduction of ucOC especially in older women ( age ≥65 ) . Furthermore , the groups which have “ A ” OUTPUT: A meta- analysis study , but not a systematic review study , showed efficacy against vertebral and non-vertebral fractures mainly in postmenopausal women with osteoporosis . There was no available evidence for men with osteoporosis . The present review of the literature revealed some evidence of a positive effect of menatetrenone on the skeleton of postmenopausal women and in patients treated with glucocorticoid . EXPERT OPINION Menatetrenone is considered to be a second-line medicine for postmenopausal osteoporotic women with an increased risk for vertebral fractures INPUT: We have recently demonstrated that glucocorticoid ( GC ) suppresses bone formation and enhances bone resorption , with result ant bone loss . This altered bone turnover is not due to the action of parathyroid hormone ( PTH ) , but appears to be related to the suppression of osteoprotegerin ( OPG ) . As vitamin K2 ( menatetrenone ) has been used for the treatment of osteoporosis , the present study was carried out to evaluate the effect of vitamin K2 on GC-induced bone loss . Twenty patients with chronic glomerulonephritis treated with GC for the first time were chosen for this study . Ten patients received GC alone ( group A ) and the other 10 patients each received 15 mg of vitamin K2 per day in addition to GC ( group B ) . Markers of bone metabolism , including serum OPG , osteocalcin ( OC ) , bone-specific alkaline phosphatase activity ( BAP ) , PTH , tartrate-resistant acid phosphatase ( TRAP ) , and bone mineral density ( BMD ) , were measured before and during the treatment . OPG was significantly decreased in group A ( P < 0.001 ) , while no significant change was seen in group B. TRAP was markedly increased in both groups , more particularly in group A ( P < 0.01 ) . PTH was decreased in group A , but was increased in group B. OC was decreased at month 1 but subsequently increased until month 12 in both groups . BAP had decreased at month 3 in group A ( P < 0.05 ) , but not in group B. BMD of the lumbar spine was significantly reduced after 6 months ( P < 0.01 ) , and 12 months ( P < 0.001 ) of treatment in group A , whereas there was no remarkable change in group B. The present study demonstrated that the inhibition exerted by vitamin K2 of the reduction in OPG induced by GC may , at least in part , play a role in the prevention and treatment of GC-induced bone loss BACKGROUND Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption . In a phase 2 clinical trial , strontium ranelate , an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption , has been shown to reduce the risk of vertebral fractures and to increase bone mineral density . METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial , we r and omly assigned 1649 postmenopausal women with osteoporosis ( low bone mineral density ) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years . We gave calcium and vitamin D supplements to both groups before and during the study . Vertebral radiographs were obtained annually , and measurements of bone mineral density were performed every six months . RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group , with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period ( relative risk , 0.59 ; 95 percent confidence interval , 0.48 to 0.73 ) . Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck ( P<0.001 for both comparisons ) . There were no significant differences between the groups in the incidence of serious adverse events . CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures It has been previously shown that the level of circulating undercarboxylated osteocalcin ( ucOC ) is elevated in elderly women in comparison with young , healthy , premenopausal ones . To underst and the mechanism of the increase in the ucOC in the elderly and to assess its potential consequences on bone fragility , we have measured ucOC in the sera of 195 elderly institutionalized women 70 - 101 yr of age . In 45 women ( 23 % ) serum ucOC was above the upper limit of the normal range for young women . The level of ucOC was negatively correlated with 25OHD ( r = -0.32 , P < 0.001 ) even after excluding the effect of age , parathyroid hormone ( PTH ) , and creatinine by partial correlation ( r = -0.24 , P < 0.002 ) . During an 18-mo follow-up , 15 women sustained a hip fracture and their baseline ucOC level was higher ( P < 0.01 ) in women who subsequently sustained hip fracture than in the nonfracture group contrasting with no significant differences for serum calcium , phosphate , alkaline phosphatase , creatinine , PTH , 250HD , and total and carboxylated OC . The risk of hip fracture was increased in women with elevated ucOC ( relative ratio 5.9 , 99.9 % Cl 1.5 - 22.7 , P < 0.001 ) . During 1 yr of calcium/vitamin D2 treatment , ucOC decreased ( P < 0.05 ) , especially in those with the initially increased values ( from 2.22 + /- 0.35 to 1.41 + /- 0.29 ng/ml , P < 0.005 ) contrasting with an increase in the placebo group ( P < 0.05 ) . In conclusion , the increase in ucOC in the elderly reflects not only some degree of vitamin K deficiency but also their poor vitamin D status , suggesting that vitamin D may be important , either directly or indirectly through its effect on bone turnover , for OUTPUT:

This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss . In the case of the latter , there is a strong effect on incident fractures among Japanese patients

MS2_dynamic_1_shot6

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: The relative accuracy of r and omized control trials ( RCTs ) and historical control trials ( HCTs ) in determining effective therapies has not been compared since there is no external verification of efficacy . We review ed six therapies studied by both methods . Most HCTs concluded therapy was better than control , but few RCTs agreed . We calculated sensitivity and specificity for each type of trial by combining published results with all possible combinations of effectiveness . The sensitivity of HCTs was 0.80 to 1.00 ( mean , 0.90 ) and specificity was 0.0 to 0.27 ( mean , 0.11 ) . The sensitivity of RCTs was 0.0 to 0.27 ( mean , 0.12 ) and specificity was 0.67 to 1.00 ( mean , 0.88 ) . Defects of RCTs are more easily corrected than those of HCTs . Readers should consider trial design and the probability of errors when deciding how much credence to give to a clinical trial CONTEXT Medical evidence may be biased over time if completion and publication of r and omized efficacy trials are delayed when results are not statistically significant . OBJECTIVE To evaluate whether the time to completion and the time to publication of r and omized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials . DESIGN Prospect i ve cohort of r and omized efficacy trials conducted by 2 trialist groups from 1986 to 1996 . SETTING Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health . PATIENTS A total of 109 efficacy trials ( total enrollment , 43708 patients ) . MAIN OUTCOME MEASURES Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer- review ed publication assessed with survival analysis . RESULTS The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm ( 6.5 vs 4.3 years , respectively ; P<.001 ; hazard ratio for time to publication for positive vs negative trials , 3.7 ; 95 % confidence interval [ CI ] , 1.8 - 7.7 ) . This difference was mostly attributable to differences in the time from completion to publication ( median , 3.0 vs 1.7 years for negative vs positive trials ; P<.001 ) . On average , trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results ( median , 2.3 vs 2.5 years ; P=.045 ) , but long-protracted trials often had low event rates and failed to reach statistical significance , while trials that were terminated early had significant results . Positive trials were su bmi tted for publication significantly more rapidly after completion than were negative trials ( median , 1.0 vs 1.6 years ; P=.001 ) and were published more rapidly after su bmi ssion ( median , 0.8 vs 1.1 years ; P=.04 ) . CONCLUSION Among r and omized efficacy trials , there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up Meta-analytic investigations sometimes use assessment s of research quality according to a formal protocol as a tool for improving research synthesis . We asked whether a particular quality scoring system could have a direct use in adjusting the summary estimates of a treatment difference . In an empirical study of the relation of quality scores to treatment differences in published meta-analyses of 7 groups of controlled r and omized clinical trials comprising 107 primary studies , we found no relation between treatment difference and overall quality score . We also found no relation between quality score and variation in treatment difference . The level of quality scores has increased at a rate of 9 % per decade for three decades , averaging 0.51 on a scale of 0 to 1 for the 1980s , and leaving much room for improvement . Nevertheless , attention to quality of studies by editors , review ers , and authors may be raising both the level of research done and quality of the reports OBJECTIVE To determine whether crossover trials with simple pooling of data over different study periods leads to a different estimate of treatment effect compared with parallel group trials in infertility research using pregnancy as the outcome measure . DESIGN An observational study using nine overviews that included trials with both crossover and parallel group design s. These overviews comprised 17 crossover and 17 parallel group trials . In total , there were 5,291 outcomes including 775 pregnancies . The association between study design and treatment effect estimate was analyzed using multiple logistic regression , controlling for differences in the therapeutic interventions and variations in the method ological quality of the trials . SETTING Infertile patients in an academic research environment . PATIENTS Infertile patients undergoing treatment efficacy evaluation in controlled trials . INTERVENTIONS R and om allocation to a variety of treatments including clomiphene citrate , hCG , IUI , tamoxifen , and bromocriptine . MAIN OUTCOME MEASURE Estimate of bias between study design s , based on the interaction of study design and treatment in the logistic regression model . RESULTS Crossover trials produced a larger average estimate of treatment effect compared with trials with a parallel group design , overestimating the odds ratio by 74 % ( 95 % confidence interval , 2 % to 197 % ) . CONCLUSION The use of a crossover design for evaluating infertility treatments with outcomes that prevent patients from completing later phases of the trial should be avoided because it leads to exaggerated estimates of treatment effect and may result in erroneous inferences and clinical decisions . Furthermore , the type of study design should be taken into account when assessing the method ological quality of therapy trials in infertility To compare the use of r and omized controls ( RCTs ) and historical controls ( HCTs ) for clinical trials , we search ed the literature for therapies studied by OUTPUT: Some of these differences were due to a poorer prognosis in the control groups in the non-r and omised trials . Comparisons of adequately and inadequately concealed allocation in r and omised trials of the same intervention provided high quality evidence that concealment can be crucial in achieving similar treatment groups and , therefore , unbiased estimates of treatment effects . Studies with inadequate concealment tended to overestimate treatment effects . Comparisons of high and low quality trials of the same intervention have found important differences in estimates of effect , but it is not possible to determine the extent to which these differences can be attributed to r and omisation or concealment of allocation . Omitting comparisons between r and omised trials and non-r and omised trials using historical controls did not substantially alter the results or conclusions of our review . On average , non-r and omised trials and r and omised trials with inadequate concealment of allocation tend to result in larger estimates of effect than r and omised trials with adequately concealed allocation . However , it is not generally possible to predict the magnitude , or even the direction , of possible selection biases and consequent distortions of treatment effects INPUT: To compare the use of r and omized controls ( RCTs ) and historical controls ( HCTs ) for clinical trials , we search ed the literature for therapies studied by both methods . We found six therapies for which 50 RCTs and 56 HCTs were reported . Forty-four of 56 HCTs ( 79 percent ) found the therapy better than the control regimen , but only 10 of 50 RCTs ( 20 percent ) agreed . For each therapy , the treated patients in RCTs and HCTs of the same therapy was largely due to differences in outcome for the control groups , with HCT control patients generally doing worse than the RCT control groups . Adjustment of the outcomes of the HCTs for prognostic factors , when possible , did not appreciably change the results . The data suggest that biases in patient selection may irretrievably weight the outcome of HCts in favor of new therapies . RCTs may miss clinical ly important benefits because of inadequate attention to sample size . The predictive value of each might be improved by reconsidering the use of p less than 0.05 as the significance level for all types of clinical trials , and by the use of confidence intervals around estimates of treatment effects A clinical trial , aim ed at secondary prevention of low-back pain , was performed in 142 hospital employees reporting at least three annual episodes of this condition . Participants were r and omly assigned to one of three groups : a calisthenics program ( CAL ) for 3 months with biweekly sessions of flexion exercises , a back school program ( 5 sessions ) , and a control group . The effectiveness of the two intervention programs was evaluated over a 1-year period . Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected . A monthly surveillance for the whole year showed a mean of 4.5 “ painful months ” in the CAL group versus 7.3 and 7.4 months in the back school and control groups , respectively ( P < 0.0001 ) . The superiority of the CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength . The increased trunk flexion was associated with the rate of participation in the CAL sessions . Further research is needed to answer the question of “ intensity versus type of exercise ” by comparing different intervention programs , with similar intensity Study Design . The study was carried out as an open , r and omized , multicenter , parallel‐group study with an observation period of 12 months . Four Norwegian physiotherapy institutes took part . Patients were subsequently followed for 12 months of home exercise on their own , without the supervision of a physiotherapist . Objectives . 1 ) To investigate and compare the effects of two different exercise programs on low back problems in patients after a 1‐year training program under the supervision of a physiotherapist . 2 ) To investigate the effect supervision by , and motivation from , physiotherapists has on training compliance and efficacy . Summary of Background Data . After ordinary physiotherapy treatment for low back problems , patients were r and omly allocated either to a conventional training program design ed by physiotherapists or to a training program using a new Norwegian‐developed training apparatus called the TerapiMaster . The study included 153 patients with low back problems , all of whom had been referred to physiotherapy by their general practitioners . One hundred twenty‐six patients were followed for an additional 12 months when performing home exercise programs on their own . Methods . Monitoring patient satisfaction with the training program , compliance with the program , and absenteeism from work during the training period . Results . Patient satisfaction with both training programs was high , with about 83 % of participating patients completing the study in accordance with the protocol . Mean absenteeism ( SD ) during the preceding year totaled 82.5 days ( 19.8 ) in the conventional training group and 61.6 days ( 14.7 ) in the TerapiMaster group . Significant reductions to 17.2 days ( 6.0 ) and 15.4 days ( 5.3 ) in the two groups , respectively , were recorded during the training period , corresponding to a 75 % to 80 % reduction compared with the preceding 1‐year period . Mean absenteeism showed a further significant decline during the 12‐month period without supervised training . The average values were 9.9 days ( 3.2 ) for conventional training and 9.3 days ( 3.1 ) for the TerapiMaster , respectively . Conclusions . Both exercise programs reduced absenteeism significantly ( 75‐80 % ) . No difference in the effects of the two different programs was discernible . Regular follow‐up through encouragement and variation in the training programs appear to be important factors for motivating patients to adhere to regular exercise programs for low back problems . This thesis was corroborated by the 12‐month study of unsupervised exercise CONTEXT Low back pain is a frequent and costly health problem . Prevention of low back pain is important both for the individual patient and from an economic perspective . OBJECTIVE To assess the efficacy of lumbar supports and education in the prevention of low back pain in industry . DESIGN A r and omized controlled trial with a factorial design . SETTING The cargo department of an airline company in the Netherl and s. PARTICIPANTS A total of 312 workers were r and omized , of whom 282 were available for the 6-month follow-up . INTERVENTIONS Subjects were r and omly assigned to 4 groups : ( 1 ) education ( lifting instructions ) and lumbar support , ( 2 ) education , ( 3 ) lumbar support , and ( 4 ) no intervention . Education consisted of 3 group sessions on lifting techniques with a total duration of 5 hours . Lumbar supports were recommended to be used during working hours for 6 months . MAIN OUTCOME MEASURES Low back pain incidence and sick leave because of back pain during the 6-month intervention period . RESULTS Compliance with wearing the lumbar support at least half the time was 43 % . In the 282 subjects for whom data were available , no statistically significant differences in back pain incidence ( 48 [ 36 OUTPUT:

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

MS2_dynamic_1_shot7

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: BACKGROUND Better self management could improve quality of life ( QoL ) and reduce hospital admissions in chronic obstructive pulmonary disease ( COPD ) , but the best way to promote it remains unclear . AIM To explore the feasibility , effectiveness and cost effectiveness of a novel , layperson-led , theoretically driven COPD self-management support programme . DESIGN AND SETTING Pilot r and omised controlled trial in one UK primary care trust area . METHOD Patients with moderate to severe COPD were identified through primary care and r and omised 2:1 to the 7-week-long , group intervention or usual care . Outcomes at baseline , 2 , and 6 months included self-reported health , St George 's Respiratory Question naire ( SGRQ ) , EuroQol , and exercise . RESULTS Forty-four per cent responded to GP invitation , 116 were r and omised : mean ( st and ard deviation [ SD ] ) age 69.5 ( 9.8 ) years , 46 % male , 78 % had unscheduled COPD care in the previous year . Forty per cent of intervention patients completed the course ; 35 % attended no sessions ; and 78 % participants completed the 6-month follow-up question naire . Results suggest that the intervention may increase both QoL ( mean EQ-5D change 0.12 ( 95 % confidence interval [ CI ] = -0.02 to 0.26 ) higher , intervention versus control ) and exercise levels , but not SGRQ score . Economic analyses suggested that with thresholds of £ 20 000 per quality -adjusted life-year gained , the intervention is likely to be cost-effective . CONCLUSION This intervention has good potential to meet the UK National Institute for Health and Clinical Excellence criteria for cost effectiveness , and further research is warranted . However , to make a substantial impact on COPD self-management , it will also be necessary to explore other ways to enable patients to access self-management education Aims : The main objective of this study was to investigate whether a comprehensive self-management programme , including self-treatment guidelines for exacerbations and a fitness programme , is an efficient treatment option for chronic obstructive pulmonary disease ( COPD ) patients . Method : We r and omly allocated 248 COPD patients to either self-management ( 127 ) or usual care ( 121 ) . Data on preference-based utilities ( EuroQol-5D ) , health-related quality of life ( HRQoL ) , health-care re source use and productivity losses associated with exacerbations were prospect ively collected . Quality -adjusted life years ( QALYs ) were calculated . The economic analysis took the societal perspective and the observation period was one year . Results : As we observed that the groups were equally effective in terms of QALYs and HRQoL ( SGRQ ) , we described a cost minimization analysis only . The self-management programme-specific costs amounted to 6642 per patient . In the base-case cost analysis , the incremental cost difference amounted to 838 per patient per year in favour of usual care . When only direct medical costs were included , the incremental annual cost of self-managementrelative to usual care was 179 per person per year . If time costs for the fitness programme were set to zero , the costs for self-management diminished to 542 . Sensitivity analysis showed that these results were robust to changes in the underlying assumptions . Conclusion : We conclude that the COPE self-management programme is not an efficient treatment option for moderate to severe COPD patients who rate their HRQoL relatively high . The programme was twice as expensive as usual care and had no measurable beneficial effects on QALYs or Objectives Pulmonary rehabilitation ( PR ) provides benefit for patients with chronic obstructive pulmonary disease ( COPD ) in terms of quality of life ( QoL ) and exercise capacity ; however , the effects diminish over time . Our aim was to evaluate a maintenance programme for patients who had completed PR . Setting Primary and secondary care PR programmes in Norfolk . Participants 148 patients with COPD who had completed at least 60 % of a st and ard PR programme were r and omised and data are available for 110 patients . Patients had greater than 20 pack year smoking history and less than 80 % predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection . Interventions Patients were r and omised to receive a maintenance programme or st and ard care . The maintenance programme consisted of 2 h ( 1 h individually tailored exercise training and 1 h education programme ) every 3 months for 1 year . Primary and secondary outcome measures The Chronic Respiratory Question naire ( CRQ ) ( primary outcome ) , endurance shuttle walk test ( ESWT ) , EuroQol ( EQ5D ) , hospital anxiety and depression score ( HADS ) , body mass index ( BMI ) , body fat , activity levels ( overall score and activity diary ) and exacerbations were assessed before and after 12 months . Results There was no statistically significant difference between the groups for the change in CRQ dyspnoea score ( primary end point ) at 12 months which amounted to 0.19 ( −0.26 to 0.64 ) units or other domains of the CRQ . There was no difference in the ESWT duration ( −10.06 ( −191.16 to 171.03 ) seconds ) , BMI , body fat , EQ5D , MET-minutes , activity rating , HADS , exacerbations or admissions . Conclusions A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months . We do not recommend that our maintenance programme is adopted . Other methods of sustaining the benefits of PR are required . Trial registration number NCT00925171 The Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) serves as a guide to treat and manage different severity classes of patients with COPD . It was suggested that the five categories of FEV1 % predicted ( GOLD 0–4 ) , can be applied OUTPUT: Meta-analyses of COPD stages utility values showed influence of airway obstruction on utility value . INPUT: BACKGROUND There is some evidence that quality of life ( QOL ) in patients with chronic obstructive pulmonary disease ( COPD ) may predict clinical outcomes and use of re sources . This study examined whether QOL scores could prospect ively predict re-admission for COPD or death within 12 months of an original admission , and whether QOL scores predicted home nebuliser provision . METHODS The study was carried out in all acute medical wards of Aberdeen Royal Infirmary , Woodend and City Hospitals , Aberdeen over 12 months . A total of 377 patients admitted with an exacerbation of COPD were identified in this time , 111 of whom were not included in the study because they refused the interview or died before discharge . The remaining 266 patients completed the St George 's Respiratory Question naire ( SGRQ ) . Information on spirometric parameters , nebuliser provision at discharge , provision of domiciliary oxygen , and re-admission within 12 months was collected from patient notes . RESULTS The mean age of the patients was 68 years and 53 % were men . The mean ( SD ) forced expiratory volume in one second ( FEV1 ) was 38.8 (18.0)% predicted and forced vital capacity ( FVC ) was 58.9 (23.8)% predicted . Higher ( worse ) scores on the SGRQ were significantly related to re-admission for COPD in the next 12 months ( difference = 4.8 , 95 % CI 1.6 to 8.0 ) . Patients who were re-admitted and died from COPD did not differ in SGRQ scores from those who were re-admitted and survived for more than 12 months . Re-admission was not related to sex , age , or pulmonary function . One hundred and thirty eight patients did not have a home nebuliser before admission . Of these , 14 were provided with a home nebuliser at discharge . Patients provided with nebulisers had significantly worse SGRQ scores and worse FVC . The 41 patients given domiciliary oxygen did not differ in SGRQ or spirometric parameters . Logistic regression analysis of the three SGRQ subscales ( Symptom , Impact and Activity ) , adjusting for lung function , age and sex , showed that all three subscales were significantly related to hospital readmission and that Impact scores were related to nebuliser provision . Women did not differ from men in Symptom scores on the SGRQ but differed markedly on the Activity and Impact scales . CONCLUSIONS It is concluded that poor scores on the SGRQ , a QOL scale which measures patient distress and coping , are associated with re-admission for COPD and use of re sources such as nebulisers , independent of physiological measures of disease severity PURPOSE Self-directed and supervised exercise were compared with usual care in a clinical trial design ed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer . PATIENTS AND METHODS One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life , aerobic capacity , and body weight . Participants were r and omly allocated to one of three intervention groups : usual care ( control group ) , self-directed exercise , or supervised exercise . Quality of life , aerobic capacity , and body weight measures were repeated at 26 weeks . The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks . RESULTS Physical functioning in the control group decreased by 4.1 points , whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups , respectively ( P = .04 ) . Post hoc analysis showed a moderately large ( and clinical ly important ) difference between the self-directed and control groups ( 9.8 points ; P = .01 ) and a more modest difference between the supervised and control groups ( 6.3 points ; P = .09 ) . No significant differences between groups were observed for changes in quality of life scores . In a secondary analysis of participants stratified by type of adjuvant therapy , supervised exercise improved aerobic capacity ( + 3.5 mL/kg/min ; P = .01 ) and reduced body weight ( -4.8 kg ; P < .05 ) compared with usual care only in participants not receiving chemotherapy . CONCLUSION Physical exercise can blunt some of the negative side effects of breast cancer treatment , including reduced physical functioning . Self-directed exercise is an effective way to improve physical functioning compared with usual care . In participants not receiving chemotherapy , supervised exercise may increase aerobic capacity and reduce body weight compared with usual care We have developed a rehabilitation programme at home and have investigated its effects on quality of life ( QOL ) , lung function , and exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . We studied 43 patients with severe airflow obstruction : forced expiratory volume in one second ( FEV1 ) 1.3 + /- 0.4 l ( mean + /- SD ) , FEV1/inspiratory vital capacity ( IVC ) 37 + /- 7.9 % . After stratification , 28 patients were r and omly allocated in a home rehabilitation programme for 12 weeks . Fifteen patients in a control group received no rehabilitation . The rehabilitation group received physiotherapy by the local physiotherapist , and supervision by a nurse and a general practitioner . Quality of life was assessed by the four dimensions of the Chronic Respiratory Question naire ( CRQ ) . We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea , emotion , and mastery . Lung function showed no changes in the rehabilitation group . The exercise tolerance improved significantly in the rehabilitation group compared to the control group . The improvement in quality of life was not correlated with the improvement in exercise tolerance . Rehabilitation of COPD patients at home may improve quality of life ; this improvement is not correlated with an OUTPUT:

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

MS2_dynamic_1_shot8

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: CONTEXT The generalized type of social phobia ( social anxiety disorder ) is a severe and often disabling form of social anxiety that affects approximately 5 % of the general population . Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition , but neither has achieved widespread use . OBJECTIVE To compare the efficacy of paroxetine , a selective serotonin reuptake inhibitor , with placebo in adults with generalized social phobia . DESIGN Twelve-week , multicenter , r and omized , double-blind trial . SETTING Thirteen centers across the United States and 1 in Canada . PARTICIPANTS Between April 13 , 1995 , and February 28 , 1996 , 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for generalized social phobia were r and omized ( and 183 returned for at least 1 efficacy assessment ) to treatment . INTERVENTION After a 1-week , single-blind , placebo , run-in period , patients received a double-blind , 11-week course of either paroxetine or matching-image placebo . The initial daily dosage of paroxetine ( or placebo ) was 20 mg with increases of 10 mg/d weekly ( flexible dosing to a maximum of 50 mg/d ) permitted after the second week of treatment . MAIN OUTCOME MEASURES Number of responders based on the Clinical Global Impression Global Improvement Item ( " much improved " or " very much improved " ) ; mean change from baseline on the Liebowitz Social Anxiety Scale total score . RESULTS Fifty ( 55.0 % ) of 91 persons taking paroxetine and 22 ( 23.9 % ) of 92 persons taking placebo were much improved or very much improved at the end of treatment ( odds ratio [ OR ] , 3.88 ; 95 % confidence interval [ CI ] , 2.81 - 5.36 ) . Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1 % ( the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up ) in the paroxetine group compared with 17.4 % ( the mean baseline score of 83.5 declined 14.5 points at follow-up ) in the placebo group , a difference of 21.7 % ( 95 % CI , 8.7%-34.7 % ) favoring paroxetine . CONCLUSIONS Paroxetine is an effective treatment for patients with generalized social phobia . Short-term ( ie , 11-week ) treatment results in substantial and clinical ly meaningful reductions in symptoms and disability . Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques Rationale Seasonal affective disorder ( SAD ) is a relatively common cyclical depressive illness characterized by seasonal depressions during winter . The disorder is commonly responsive to light therapy , but antidepressant drug efficacy has not been definitely established . Serotonin selective re-uptake inhibitors are potentially efficacious treatments for SAD . Objectives The objective of this study was to evaluate the efficacy , tolerability and safety of sertraline treatment for SAD . Methods One hundred and eighty seven out patients with seasonal pattern recurrent winter depression ( DSM-III-R defined ) and a minimum 29-item Hamilton depression scale ( SIGH-SAD version ) score of 22 were r and omized to 8 weeks treatment with either sertraline or placebo in a double-blind , multi-country , multi-center , parallel-group , flexible dose ( 50–200 mg once daily ) study . Efficacy was investigated using physician and patient-rated scales measuring depression , anxiety and symptoms characteristic of seasonal affective disorder . Results Sertraline produced a significantly greater response than placebo at endpoint as measured by changes in the 29-item and 21-item Hamilton depression scales , the clinical global impression ( CGI ) severity scale , the Hamilton anxiety scale , and the hospital anxiety and depression scale . The proportion of sertraline-treated subjects achieving a response on the CGI improvement rating ( ratings of 1 or 2 ) at endpoint ( last observation carried forward ) was significantly greater than that of the placebo group . Overall sertraline was well tolerated with the most frequent placebo adjusted adverse events , being nausea , diarrhea , insomnia and dry mouth . Adverse events were mostly mild to moderate and transient . Conclusions Sertraline pharmacotherapy has been demonstrated to be an effective and well-tolerated therapy for out patients with SAD . As such , sertraline offers an important pharmacological option in the clinical management of this condition The efficacy of paroxetine in the treatment of obsessive-compulsive disorder in Western population s is well established . The present study compares the efficacy and safety of paroxetine with placebo in the treatment of obsessive-compulsive disorder in Japanese patients . Patients aged 16 years or older who met Diagnostic and Statistical Manual of Mental Disorders ( 4th edn ; DSM-IV ) criteria for obsessive-compulsive disorder and had a Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) score of > /=16 were r and omized to receive 12 weeks ' therapy in a double-blind manner . Paroxetine 20 - 50 mg/day or placebo was administered following a 1 week , placebo run-in phase . One hundred and ninety-one patients were r and omized to either paroxetine or placebo , 188 patients were assessed as the full analysis set ( FAS ) and 144 patients completed the 12 week study . After adjustment for the Y-BOCS total score at baseline , reductions in obsessive-compulsive total score at week 6 and at OUTPUT: Systematic assessment led to higher rates than less systematic assessment . Conclusion : Adverse effect profiles reported in clinical trials are strongly influenced by expectations from investigators and patients . This difference can not be attributed to ascertainment methods . Adverse effect patterns of the drug group are closely related to adverse effects of the placebo group . These results question the validity of the assumption that adverse effects in placebo groups reflect the ‘ drug-unspecific effects ’ INPUT: Abstract This long-term extension of an 8-week r and omized , naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam ( n = 47 ) and paroxetine ( n = 37 ) over a 3-year total treatment duration . Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine ( both taken at bedtime ) . This study reports data from the long-term period ( 34 months ) , following the initial 8-week treatment phase . Thus , total treatment duration was 36 months . Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine , but patients with partial primary treatment success were switched to the combination therapy . At initiation of the long-term study , the mean doses of clonazepam and paroxetine were 1.9 ( SD , 0.30 ) and 38.4 ( SD , 3.74 ) mg/d , respectively . These doses were maintained until month 36 ( clonazepam 1.9 [ SD , 0.29 ] mg/d and paroxetine 38.2 [ SD , 3.87 ] mg/d ) . Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine ( mean difference : CGI-Severity scale −3.48 vs −3.24 , respectively , P = 0.02 ; CGI-Improvement scale 1.06 vs 1.11 , respectively , P = 0.04 ) . Both treatments similarly reduced the number of panic attacks and severity of anxiety . Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine ( 28.9 % vs 70.6 % , P < 0.001 ) . The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course . There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events Background Anxiety disorders are among the most common psychiatric illnesses , with generalized anxiety disorder ( GAD ) being one of the most common . Sleep disturbances are highly prevalent in GAD patients . While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials , mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin . Thus , the objective of this study was to model the longitudinal latent effect of pregabalin or usual care ( UC ) therapies on changes in sleep in out patients with GAD under routine clinical practice . Methods Male and female GAD out patients , aged 18 years or above , from a 6-month prospect i ve noninterventional trial were analyzed . Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms ( assessed with Hamilton Anxiety Scale ) and sleep disturbances ( assessed with Medical Outcomes Study -Sleep Scale [ MOS-S ] ) were estimated by a conditional latent curve model applying structural equation modeling . Results A total of 1,546 pregabalin-naïve patients were analyzed , 984 receiving pregabalin and 562 UC . Both symptoms of anxiety and sleep disturbances were significantly improved in both groups , with higher mean ( 95 % confidence interval ) score reductions in subjects receiving pregabalin : −15.9 ( −15.2 ; −16.6 ) vs −14.5 ( −13.5 ; −15.5 ) , P=0.027 , in Hamilton Anxiety Scale ; and −29.7 ( −28.1 ; −31.3 ) vs −24.0 ( −21.6 ; −26.4 ) , P<0.001 , in MOS-S. The conditional latent curve model showed that the pregabalin effect on sleep disturbances was significant ( γ = −3.99 , P<0.001 ) , after discounting the effect on reduction in anxiety symptoms . A mediation model showed that 70 % of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement . Conclusion A substantial proportion of the incremental improvements in anxiety-related sleep disturbances with pregabalin vs UC were explained by its direct effect , not mediated by improvements in anxiety symptoms Background : Remission has become one of the leading outcome criteria in clinical trials . Data collected by this research group assessed the rate of remission after 6 months of treatment of generalized anxiety disorder ( GAD ) with venlafaxine XR , to search for predictors of remission and to define how early on in treatment later remission can be predicted . Method : Two hundred sixty-eight patients with a GAD diagnosis enrolled into an open-label 6-month-treatment trial with venlafaxine XR ( 75 - 225 mg/day ) . Remission was defined by a Hamilton anxiety scale total score ≤7 . Logistic regression approaches were used to find out how early on in treatment later remission could be predicted , as well as to determine predictors of remission . In addition , adverse events were also followed over time . Results : While the total enrolled patient sample ( n = 268 ) had a remission rate of 53 % , 6-month completers ( n = 159 ) had a remission rate of 79 % . The only statistically significant predictor of remission , independent of baseline anxiety and depression levels , was a low Eysenck neuroticism score . The remission status outcome could best be predicted after 8 weeks of treatment when a CGI-I score of 1 or 2 predicted later remission with 78 % accuracy and later nonremission with 91 % accuracy . The incidence of adverse events decreased over the 6-month period , with sexual adverse events decreasing the least . Conclusion : The only significant predictor of remission was a OUTPUT:

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

MS2_dynamic_1_shot9

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: OBJECTIVES To assess the optimal stroke prevention treatment for patients with atrial fibrillation ( AF ) and a low-medium risk ( < or = 4 % ) of stroke . DESIGN A total of 668 patients with persistent or permanent AF , without an indication for full dose and with adequate rate control on sotalol , were r and omized to warfarin 1.25 mg + aspirin 75 mg daily ( W/A , 334 patients ) or no anticoagulation ( C , 334 patients ) . The mean follow-up period was 33 months . The protocol intended to verify a 37 % relative risk reduction provided a 4 % stroke incidence in the C group . RESULTS The stroke incidence was less in the W/A group , although the reduction was not statistically significant ( W/A 9.6 % versus C 12.3 % ) . Four haemorrhagic strokes were identified , two in each group . Secondary end-points were transient ischaemic attacks ( TIA ) ( W/A 3.3 % versus C 4.5 % ) , all cause mortality ( W/A 9.3 % versus C 10.8 % ) , cardiovascular morbidity ( W/A 17.7 % versus C 22.2 % ) and the combination of stroke + TIA ( W/A 11.7 % versus C 16.5 % ) . Bleedings were documented in 19 versus four patients ( W/A 5.7 % versus C 1.2 % ) ( P = 0.003 ) , although none fatal . Sinus rhythm ( SR ) was recorded occasionally in 68 patients ( W/A 9.6 % versus C 10.8 % ) . The stroke incidence tended to be higher in those with SR than without , 16.2 % versus 10.4 % . CONCLUSIONS Our results were inconclusive , but consistent with a small beneficial effect of W/A for reduction of stroke and major vascular events in AF patients at moderate risk . The low-dose regiment produced , however , a significantly increased risk of bleedings . Documented SR occasionally recorded may represent a sub population that warrants full dose warfarin BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin . METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P<0.001 ) , female sex ( RR=1.6 , P=0.01 ) , history of hypertension ( RR=2.0 , P<0.001 ) , systolic blood pressure > 160 mm Hg ( RR=2.3 , P<0.001 ) , and prior stroke or transient ischemic attack ( RR=2.9 , P<0.001 ) were independently associated with increased stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P<0.001 ) . CONCLUSIONS Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation Background Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke . Methods and Main Results . The Stroke Prevention in Atrial Fibrillation Study , a multicenter , r and omized trial , compared 325 mg/day aspirin ( double-blind ) or warfarin with placebo for prevention of ischemic stroke and systemic embolism ( primary events ) , and included 1,330 in patients and out patients with constant or intermittent atrial fibrillation . During a mean follow-up of 1.3 years , the rate of primary events in patients assigned to placebo was 6.3 % per year and was reduced by 42 % in those assigned to aspirin ( 3.6 % per year , p = 0.02 ; 95 % confidence interval , 9–63 % ) . In the subgroup of warfarin-eligible patients ( most less than 76 years old ) , warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67 % ( warfarin versus placebo , 2.3 % versus 7.4 % per year , p = 0.01 ; 95 % confidence interval , 27–85 % ) . Primary events or death were reduced 58 % ( p = 0.01 ) by warfarin and 32 % ( p = 0.02 ) by aspirin . The risk of OUTPUT: The observed rates of intracranial and extracranial hemorrhage were not significantly increased by OAC therapy , but the confidence intervals were wide . Treatment with adjusted-dose warfarin to achieved INRs of 2 to 3 reduces stroke , disabling or fatal stroke , and death for patients with non-valvular AF . The benefits were not substantially offset by increased bleeding among these participants in r and omized clinical trials . INPUT: Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation ( AF ) . We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation . Methods and results Patients r and omized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) trial ( n = 14 264 ) were grouped by baseline AF category : paroxysmal or persistent . Multivariable adjustment was performed to compare thrombo-embolic events , bleeding , and death between groups , in high-risk subgroups , and across treatment assignment ( rivaroxaban or warfarin ) . Of 14 062 patients , 11 548 ( 82 % ) had persistent AF and 2514 ( 18 % ) had paroxysmal AF . Patients with persistent AF were marginally older ( 73 vs. 72 , P = 0.03 ) , less likely female ( 39 vs. 45 % , P < 0.0001 ) , and more likely to have previously used vitamin K antagonists ( 64 vs. 56 % , P < 0.0001 ) compared with patients with paroxysmal AF . In patients r and omized to warfarin , time in therapeutic range was similar ( 58 vs. 57 % , P = 0.94 ) . Patients with persistent AF had higher adjusted rates of stroke or systemic embolism ( 2.18 vs. 1.73 events per 100-patient-years , P = 0.048 ) and all-cause mortality ( 4.78 vs. 3.52 , P = 0.006 ) . Rates of major bleeding were similar ( 3.55 vs. 3.31 , P = 0.77 ) . Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment ( rivaroxaban vs. warfarin , Pinteraction = 0.6 ) . Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation , those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF Background and Purpose — We sought to investigate the apparently high risk of early death after an ischemic stroke among patients with atrial fibrillation ( AF ) , identify the main factors associated with early death , and assess the effect of treatment with different doses of subcutaneous unfractionated heparin ( UFH ) given within 48 hours . Methods — We studied the occurrence of major clinical events within 14 days among 18 451 patients from the International Stroke Trial , first for all treatment groups combined . Then , among patients with AF , we examined the effects of treatment with subcutaneous UFH started within 48 hours and continued until 14 days after stroke onset . Results — A total of 3169 patients ( 17 % ) had AF . Seven hundred eighty-four patients were allocated to UFH 12 500 IU SC BID , 773 to UFH 5000 IU SC BID , and 1612 to no heparin . Within each of these groups , half of the patients were r and omly assigned to aspirin 300 mg once daily . Compared with patients without AF , patients with AF were more likely to be female ( 56 % versus 45 % ) , to be old ( mean age , 78 versus 71 years ) , to have an infa rct on prer and omization CT ( 57 % versus 47 % ) , and to have impaired consciousness ( 37 % versus 20 % ) . The initial ischemic stroke type was more often a large-artery infa rct ( 36 % versus 21 % ) . A lacunar stroke syndrome was less common ( 13 % versus 26 % ) . Death within 14 days was more common in patients with AF ( 17 % versus 8 % ) and more often attributed to neurological damage from the initial stroke ( 10 % versus 4 % ) . The frequency of recurrent ischemic or undefined stroke was not significantly different ( 3.9 % versus 3.3 % ) . The proportion of AF patients with further events within 14 days allocated to UFH 12 500 IU ( n=784 ) , UFH 5000 IU ( n=773 ) , and to no-heparin ( n=1612 ) groups were as follows : ischemic stroke , 2.3 % , 3.4 % , 4.9 % ( P = 0.001 ) ; hemorrhagic stroke , 2.8 % , 1.3 % , 0.4 % ( P < 0.0001 ) ; and any stroke or death , 18.8 % , 19.4 % and 20.7 % ( P = 0.3 ) , respectively . No effect of heparin on the proportion of patients dead or dependent at 6 months was apparent . Conclusions — Acute ischemic stroke patients with AF have a higher risk of early death , which can be explained by older age and larger infa rcts but not by a higher risk of early recurrent ischemic stroke , although slightly more patients with AF died from a fatal recurrent stroke of ischemic or unknown type ( 1.3 % versus 0.9 % ) . In patients with AF the absolute risk of early recurrent stroke is low , and there is no net advantage to treatment with heparin . These data do not support the widespread use of intensive heparin regimens in the acute phase of ischemic stroke associated with AF BACKGROUND Few epidemiologic cohort studies have evaluated atrial flutter ( flutter ) as an arrhythmia distinct from atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to examine the clinical correlates of flutter and its associated outcomes to distinguish them from those associated with AF in OUTPUT:

These results showed that AF is an independent risk factor for MI , CV death , and CV events

MS2_dynamic_1_shot10

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: BACKGROUND Cholera is endemic in Bangladesh with epidemics occurring each year . The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting . We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and h and washing to vaccination in this setting . METHODS We did this cluster-r and omised open-label trial in Dhaka , Bangladesh . We r and omly assigned 90 clusters ( 1:1:1 ) to vaccination only , vaccination and behavioural change , or no intervention . The primary outcome was overall protective effectiveness , assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose . This study is registered with Clinical Trials.gov , number NCT01339845 . FINDINGS Of 268,896 people present at baseline , we analysed 267,270 : 94,675 assigned to vaccination only , 92,539 assigned to vaccination and behavioural change , and 80,056 assigned to non-intervention . Vaccine coverage was 65 % in the vaccination only group and 66 % in the vaccination and behavioural change group . Overall protective effectiveness was 37 % ( 95 % CI lower bound 18 % ; p=0·002 ) in the vaccination group and 45 % ( 95 % CI lower bound 24 % ; p=0·001 ) in the vaccination and behavioural change group . We recorded no vaccine-related serious adverse events . INTERPRETATION Our findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban population s with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such population s. FUNDING Bill & Melinda Gates Foundation This paper analyzes a r and omized experiment that uses novel strategies to promote h and washing with soap at critical points in time in Peru . It evaluates a large-scale comprehensive initiative that involved both community and school activities in addition to communication campaigns . The analysis indicates that the initiative was successful in reaching the target audience and in increasing the treated population 's knowledge about appropriate h and washing behavior . These improvements translated into higher self-reported and observed h and washing with soap at critical junctures . However , no significant improvements in the health of children under the age of 5 years were observed . Copyright © 2015 John Wiley & Sons , Summary Background Diarrhoea and growth faltering in early childhood are associated with subsequent adverse outcomes . We aim ed to assess whether water quality , sanitation , and h and washing interventions alone or combined with nutrition interventions reduced diarrhoea or growth faltering . Methods The WASH Benefits Bangladesh cluster-r and omised trial enrolled pregnant women from villages in rural Bangladesh and evaluated outcomes at 1-year and 2-years ' follow-up . Pregnant women in geographically adjacent clusters were block-r and omised to one of seven clusters : chlorinated drinking water ( water ) ; up grade d sanitation ( sanitation ) ; promotion of h and washing with soap ( h and washing ) ; combined water , sanitation , and h and washing ; counselling on appropriate child nutrition plus lipid-based nutrient supplements ( nutrition ) ; combined water , sanitation , h and washing , and nutrition ; and control ( data collection only ) . Primary outcomes were caregiver-reported diarrhoea in the past 7 days among children who were in utero or younger than 3 years at enrolment and length-for-age Z score among children born to enrolled pregnant women . Masking was not possible for data collection , but analyses were masked . Analysis was by intention to treat . This trial is registered at Clinical Trials.gov , number NCC01590095 . Findings Between May 31 , 2012 , and July 7 , 2013 , 5551 pregnant women in 720 clusters were r and omly allocated to one of seven groups . 1382 women were assigned to the control group ; 698 to water ; 696 to sanitation ; 688 to h and washing ; 702 to water , sanitation , and h and washing ; 699 to nutrition ; and 686 to water , sanitation , h and washing , and nutrition . 331 ( 6 % ) women were lost to follow-up . Data on diarrhoea at year 1 or year 2 ( combined ) were available for 14 425 children ( 7331 in year 1 , 7094 in year 2 ) and data on length-for-age Z score in year 2 were available for 4584 children ( 92 % of living children were measured at year 2 ) . All interventions had high adherence . Compared with a prevalence of 5·7 % ( 200 of 3517 child weeks ) in the control group , 7-day diarrhoea prevalence was lower among index children and children under 3 years at enrolment who received sanitation ( 61 [ 3·5 % ] of 1760 ; prevalence ratio 0·61 , 95 % CI 0·46–0·81 ) , h and washing ( 62 [ 3·5 % ] of 1795 ; 0·60 , 0·45–0·80 ) , combined water , sanitation , and h and washing ( 74 [ 3·9 % ] of 1902 ; 0·69 , 0·53–0·90 ) , nutrition ( OUTPUT: Conclusions Many people lack a design ated h and washing facility , but even among those with access , HWWS is poorly practised . People with access to design ated h and washing facilities are about twice as likely to wash their h and s with soap after potential faecal contact as people who lack a facility . INPUT: Vaccination of one person may prevent the infection of another either because the vaccine prevents the first from being infected and from infecting the second , or because , even if the first person is infected , the vaccine may render the infection less infectious . We might refer to the first of these mechanisms as a contagion effect and the second as an infectiousness effect . In the simple setting of a r and omized vaccine trial with households of size two , we use counterfactual theory under interference to provide formal definitions of a contagion effect and an unconditional infectiousness effect . Using ideas analogous to mediation analysis , we show that the indirect effect ( the effect of one person 's vaccine on another 's outcome ) can be decomposed into a contagion effect and an unconditional infectiousness effect on the risk difference , risk ratio , odds ratio , and vaccine efficacy scales . We provide identification assumptions for such contagion and unconditional infectiousness effects and describe a simple statistical technique to estimate these effects when they are identified . We also give a sensitivity analysis technique to assess how inferences would change under violations of the identification assumptions . The concepts and results of this paper are illustrated with hypothetical vaccine trial data BACKGROUND We evaluated the herd protection conferred by an oral cholera vaccine using 2 approaches : cluster design and geographic information system ( GIS ) design . METHODS Residents living in 3933 dwellings ( clusters ) in Kolkata , India , were cluster-r and omized to receive either cholera vaccine or oral placebo . Nonpregnant residents aged≥1 year were invited to participate in the trial . Only the first episode of cholera detected for a subject between 14 and 1095 days after a second dose was considered . In the cluster design , indirect protection was assessed by comparing the incidence of cholera among non participants in vaccine clusters vs those in placebo clusters . In the GIS analysis , herd protection was assessed by evaluating association between vaccine coverage among the population residing within 250 m of the household and the occurrence of cholera in that population . RESULTS Among 107 347 eligible residents , 66 990 received 2 doses of either cholera vaccine or placebo . In the cluster design , the 3-year data showed significant total protection ( 66 % protection , 95 % confidence interval [ CI ] , 50%-78 % , P<.01 ) but no evidence of indirect protection . With the GIS approach , the risk of cholera among placebo recipients was inversely related to neighborhood-level vaccine coverage , and the trend was highly significant ( P<.01 ) . This relationship held in multivariable models that also controlled for potentially confounding demographic variables ( hazard ratio , 0.94 [ 95 % CI , .90-.98 ] ; P<.01 ) . CONCLUSIONS Indirect protection was evident in analyses using the GIS approach but not the cluster design approach , likely owing to considerable transmission of cholera between clusters , which would vitiate herd protection in the cluster analyses . CLINICAL TRIALS REGISTRATION NCT00289224 Spatial analyses of the effect of insecticide (permethrin)-treated bed nets ( ITNs ) on nearby households both with and without ITNs was performed in the context of a large-scale , group-r and omized , controlled mortality trial in Asembo , western Kenya . Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality , moderate anemia , high-density parasitemia , and hemoglobin levels . This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs . This implies that in areas with intense malaria transmission with high ITN coverage , the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not , as commonly supposed , by simple imposition of a physical barrier protecting individuals from biting . The strength of the community effect depended upon the proportion of nearby compounds with treated nets . To maximize their public health impact , high coverage with treated nets is essential Objective To assess the efficacy of modest non-financial incentives on immunisation rates in children aged 1 - 3 and to compare it with the effect of only improving the reliability of the supply of services . Design Clustered r and omised controlled study . Setting Rural Rajasthan , India . Participants 1640 children aged 1 - 3 at end point . Interventions 134 villages were r and omised to one of three groups : a once monthly reliable immunisation camp ( intervention A ; 379 children from 30 villages ) ; a once monthly reliable immunisation camp with small incentives ( raw lentils and metal plates for completed immunisation ; intervention B ; 382 children from 30 villages ) , or control ( no intervention , 860 children in 74 villages ) . Surveys were undertaken in r and omly selected households at baseline and about 18 months after the interventions started ( end point ) . Main outcome measures Proportion of children aged 1 - 3 at the end point who were partially or fully immunised . Results Among children aged 1 - 3 in the end point survey , rates of full immunisation were 39 % ( 148/382 , 95 % confidence interval 30 % to 47 % ) for intervention B villages ( reliable immunisation with incentives ) , 18 % ( 68/379 , 11 % to 23 % ) for intervention A villages ( reliable immunisation without incentives ) , and 6 % ( 50/860 , 3 % to 9 % ) for control villages . The relative risk of complete immunisation for intervention B versus control was 6.7 ( 4.5 to 8.8 ) and for intervention B versus intervention A was 2.2 ( 1.5 to 2.8 ) . Children in areas neighbouring intervention B villages were also more likely to be fully immun OUTPUT:

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

MS2_dynamic_1_shot11

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: Background Type 2 diabetes mellitus is a worldwide challenge . Practice guidelines promote structured self-monitoring of blood glucose ( SMBG ) for informing health care providers about glycemic control and providing patient feedback to increase knowledge , self-efficacy , and behavior change . Paired glucose testing — pairs of glucose results obtained before and after a meal or physical activity — is a method of structured SMBG . However , frequent access to glucose data to interpret values and recommend actions is challenging . A complete feedback loop— data collection and interpretation combined with feedback to modify treatment — has been associated with improved outcomes , yet there remains limited integration of SMBG feedback in diabetes management . Incorporating telehealth remote monitoring and asynchronous electronic health record ( EHR ) feedback from certified diabetes educators (CDEs)—specialists in glucose pattern management — employ the complete feedback loop to improve outcomes . Objective The purpose of this study was to evaluate a telehealth remote monitoring intervention using paired glucose testing and asynchronous data analysis in adults with type 2 diabetes . The primary aim was change in glycated hemoglobin (A1c)—a measure of overall glucose management — between groups after 6 months . The secondary aims were change in self-reported Summary of Diabetes Self-Care Activities ( SDSCA ) , Diabetes Empowerment Scale , and Diabetes Knowledge Test . Methods A 2-group r and omized clinical trial was conducted comparing usual care to telehealth remote monitoring with paired glucose testing and asynchronous virtual visits . Participants were aged 30 - 70 years , not using insulin with A1c levels between 7.5 % and 10.9 % ( 58 - 96 mmol/mol ) . The telehealth remote monitoring tablet computer transmitted glucose data and facilitated a complete feedback loop to educate participants , analyze actionable glucose data , and provide feedback . Data from paired glucose testing were analyzed asynchronously using computer-assisted pattern analysis and were shared with patients via the EHR weekly . CDEs called participants monthly to discuss paired glucose testing trends and treatment changes . Separate mixed-effects models were used to analyze data . Results Participants ( N=90 ) were primarily white ( 64 % , 56/87 ) , mean age 58 ( SD 11 ) years , mean body mass index 34.1 ( SD 6.7 ) kg/m2 , with diabetes for mean 8.2 ( SD 5.4 ) years , and a mean A1c of 8.3 % ( SD 1.1 ; 67 mmol/mol ) . Both groups lowered A1c with an estimated average decrease of 0.70 percentage points in usual care group and 1.11 percentage points in the treatment group with a significant difference of 0.41 percentage points at 6 months ( SE 0.08 , t159=–2.87 , P=.005 ) . Change in medication ( SE 0.21 , t157=–3.37 , P=.009 ) was significantly associated with lower A1c level . The treatment group significantly improved on the SDSCA subscales carbohydrate spacing ( P=.04 ) , monitoring glucose ( P=.001 ) , and foot care ( P=.02 ) . Conclusions An eHealth model incorporating a complete feedback loop with telehealth remote monitoring and paired glucose testing with asynchronous data analysis significantly improved A1c levels compared to usual care . Trial Registration Clinical trials.gov NCT01715649 ; https://www . clinical trials.gov/ct2/show/NCT01715649 ( Archived by WebCite at http://www.webcitation.org/6ZinLl8D0 ) AIM This paper is a report of a study conducted to assess the effectiveness of an educational intervention for people with type 2 diabetes based on self-completed instruments to identify particular areas of self-care needs . BACKGROUND Diabetes is a dem and ing disease which requires self-care . Instruments that identify self-care needs or factors affecting self-care can be helpful to detect level of self-care , distress or knowledge among individuals with diabetes . METHODS Participants were r and omized into intervention ( n = 28 ) or control groups ( n = 25 ) . Both groups answered five vali date d instruments three times , at baseline and after 3 and 6 months , and biological measurements were conducted simultaneously . The intervention was based on an empowerment approach . The study started in November 2005 and lasted until March 2007 . FINDINGS There was no statistically significant difference between groups in level of glycated haemoglobin postintervention as it reduced statistically significantly in both groups between baseline and 3 months but increased again after 6 months . There was no statistically significant difference between groups in body mass index reduction ; the intervention group achieved a statistically significant body mass index reduction but this was unchanged in the control group . No statistically significant differences between groups were found in scores for empowerment , well-being and distress . There was a statistically significant difference between groups in knowledge postintervention . CONCLUSION Use of instruments to identify self-care needs can enable patient-tailored care as it allows direct focusing on issues that are challenging and of relevance for each individual . It seems to be feasible to use the telephone to conduct an empowering educational intervention after one meeting Purpose The purpose of this pilot study was to evaluate the effects of a culturally sensitive , empowerment-based diabetes self-management education program for Spanish-speaking Hispanic/Latinos . Methods A prospect i ve quasi-experimental repeated measures design tested the effectiveness of the ¡ Si , Yo Puedo Controlar Mi Diabetes ! diabetes self-management education program . In sum , 144 persons residing in 2 Texas counties at the Texas-Mexico border ( Starr and Hidalgo ) served as participants . Two groups were formed , an intervention and a control ( wait list ) . Clinical ( A1C ) , cognitive , attitudinal , behavioral , and cultural assessment s were OUTPUT: However , after meta- analysis , no statistically significant improvement was found for HbA1c . CONCLUSION This systematic review showed that individual strategies for DM empowerment were not effective in reducing HbA1c , despite contributing to improvements in psychosocial parameters . INPUT: Sustained improvement in blood glucose control is the only treatment outcome which will reduce or eliminate the long term complications of diabetes mellitus . We have design ed and evaluated an electronic information system which facilitates this task . The system is voice-interactive , physician directed and affords , to remote patients , 24 h access via touch-tone telephone . Accordingly , patients access the system each day to report self-measured blood glucose levels or hypoglycaemic symptoms together with dietary changes , planned exercise , stress , illness or other lifestyle events . In turn they receive immediate advice with respect to medication dosing changes , and other pertinent feedback . Preliminary system beta-testing for safety and efficacy was performed for one year in an open study of 204 patients derived from two independent , health-care environments . Among the two testing centres , over 60,000 telephone cells were received by the computer systems during the start-up year . Safety and efficacy expectations were met . In addition , prevalence of diabetes related crises ( hyperglycaemia or hypoglycaemia ) fell approximately 3-fold . Glycated haemoglobin fell significantly ( 1.0 - 1.3 % ) in patients actively using the system . In control groups of patients not actively using the system , there were no improvements in metabolic control while body weights were stable in all groups . The new system was safe and effective in our h and s and empowered our health professionals to provide improved diabetes care Background Type 2 diabetes mellitus is a worldwide challenge . Practice guidelines promote structured self-monitoring of blood glucose ( SMBG ) for informing health care providers about glycemic control and providing patient feedback to increase knowledge , self-efficacy , and behavior change . Paired glucose testing — pairs of glucose results obtained before and after a meal or physical activity — is a method of structured SMBG . However , frequent access to glucose data to interpret values and recommend actions is challenging . A complete feedback loop— data collection and interpretation combined with feedback to modify treatment — has been associated with improved outcomes , yet there remains limited integration of SMBG feedback in diabetes management . Incorporating telehealth remote monitoring and asynchronous electronic health record ( EHR ) feedback from certified diabetes educators (CDEs)—specialists in glucose pattern management — employ the complete feedback loop to improve outcomes . Objective The purpose of this study was to evaluate a telehealth remote monitoring intervention using paired glucose testing and asynchronous data analysis in adults with type 2 diabetes . The primary aim was change in glycated hemoglobin (A1c)—a measure of overall glucose management — between groups after 6 months . The secondary aims were change in self-reported Summary of Diabetes Self-Care Activities ( SDSCA ) , Diabetes Empowerment Scale , and Diabetes Knowledge Test . Methods A 2-group r and omized clinical trial was conducted comparing usual care to telehealth remote monitoring with paired glucose testing and asynchronous virtual visits . Participants were aged 30 - 70 years , not using insulin with A1c levels between 7.5 % and 10.9 % ( 58 - 96 mmol/mol ) . The telehealth remote monitoring tablet computer transmitted glucose data and facilitated a complete feedback loop to educate participants , analyze actionable glucose data , and provide feedback . Data from paired glucose testing were analyzed asynchronously using computer-assisted pattern analysis and were shared with patients via the EHR weekly . CDEs called participants monthly to discuss paired glucose testing trends and treatment changes . Separate mixed-effects models were used to analyze data . Results Participants ( N=90 ) were primarily white ( 64 % , 56/87 ) , mean age 58 ( SD 11 ) years , mean body mass index 34.1 ( SD 6.7 ) kg/m2 , with diabetes for mean 8.2 ( SD 5.4 ) years , and a mean A1c of 8.3 % ( SD 1.1 ; 67 mmol/mol ) . Both groups lowered A1c with an estimated average decrease of 0.70 percentage points in usual care group and 1.11 percentage points in the treatment group with a significant difference of 0.41 percentage points at 6 months ( SE 0.08 , t159=–2.87 , P=.005 ) . Change in medication ( SE 0.21 , t157=–3.37 , P=.009 ) was significantly associated with lower A1c level . The treatment group significantly improved on the SDSCA subscales carbohydrate spacing ( P=.04 ) , monitoring glucose ( P=.001 ) , and foot care ( P=.02 ) . Conclusions An eHealth model incorporating a complete feedback loop with telehealth remote monitoring and paired glucose testing with asynchronous data analysis significantly improved A1c levels compared to usual care . Trial Registration Clinical trials.gov NCT01715649 ; https://www . clinical trials.gov/ct2/show/NCT01715649 ( Archived by WebCite at http://www.webcitation.org/6ZinLl8D0 ) OBJECTIVE To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS For this study , 104 patients with diabetes and HbA(1c ) ( A1C ) > or = 9.0 % who received their care at a Department of Veterans Affairs medical center were recruited . All participants completed a diabetes education class and were r and omized to continue with their usual care ( n = 52 ) or receive web-based care management ( n = 52 ) . The web-based group received a notebook computer , glucose and blood pressure monitoring devices , and access to a care management website . The website provided educational modules , accepted uploads from monitoring devices , and had an internal messaging system for patients to communicate with the care manager . RESULTS OUTPUT:

In addition , the more CCM-incorporated the information technology-based interventions were , the more improvements there were in HbA1c levels . CONCLUSIONS Information technology strategies combined with the other elements of chronic care models are associated with improved glycemic control in people with diabetes . No clinical ly relevant impact was observed on low-density lipoprotein levels and blood pressure , but there was evidence that the cost of care was lower

MS2_dynamic_1_shot12

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: To better estimate how frequently patients with low serum cobalamin ( Cbl ) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency , we prospect ively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period . Baseline hematologic , neuropsychiatric , and biochemical measurements were obtained , followed by a course of parenteral Cbl therapy and re assessment . A response to Cbl therapy was defined as one or more of the following : ( 1 ) an increase in hematocrit of 0.05 or more ; ( 2 ) a decrease in mean cell volume of 5 fL or more ; ( 3 ) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear ; and ( 4 ) an unequivocal and prompt improvement of neuropsychiatric abnormalities . Of the 300 patients with serum Cbl levels less than 200 pg/mL , 86 had one or more responses to Cbl therapy and 59 had no response . In 155 , insufficient data was available . In the Cbl-responsive patients , normal values were found for the following tests : hematocrit , 44 % ; mean cell volume less than or equal to 100 fL , 36 % ; white blood cell count , 84 % ; platelet count , 79 % ; serum lactic dehydrogenase , 43 % ; and serum bilirubin , 83 % . Peripheral blood smears were nondiagnostic in 6 % when review ed by the investigators , but 33 % as reported by routine laboratories . Serum Cbl levels in the 100 to 199 pg/mL range were present in 38 % . Neuropsychiatric abnormalities were noted in 28 % , often in the absence of anemia , macrocytosis , or both . Serum levels of methylmalonic acid and /or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94 % of the Cbl-responsive patients . We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency , even if anemia , an elevated mean cell volume , a marked depression of the serum Cbl , or other classic hematologic or biochemical abnormalities are lacking . Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency BACKGROUND A self-rating inventory has been developed to measure DSM-IV and ICD-10 diagnoses of major ( moderate to severe ) depression by the patients ' self-reported symptoms . This Major Depression Inventory ( MDI ) can be scored both according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology and according to severity scales by the simple total sum of the items . METHODS The Schedule for Clinical Assessment in Neuropsychiatry ( SCAN ) was used as index of validity for the clinician 's DSM-IV and ICD-10 diagnosis of major ( moderate to severe ) depression . The sensitivity and specificity of MDI was assessed in a sample of 43 subjects covering a spectrum of depressive symptoms . RESULTS The sensitivity of the MDI algorithms for major depression varied between 0.86 and 0.92 . The specificity varied between 0.82 and 0.86 . When using the total score of MDI the optimal cut-off score was estimated 26 and the total score was shown to be a sufficient statistic . LIMITATIONS The sample of subjects was limited . Patients with psychotic depression were not included . CONCLUSION The MDI was found to have a sensitivity and specificity which is acceptable . The question naire is brief and can be scored diagnostically by the DSM-IV and ICD-10 algorithms as well as by its simple total score OBJECTIVE To measure the prevalence of cobalamin ( vitamin B12 ) deficiency in geriatric out patients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment . DESIGN Prospect i ve study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays . In patients with serum cobalamin levels < or = 300 pg/mL , the response to cobalamin treatment in the group with levels of methylmalonic acid and /or homocysteine > 3 st and ard deviations ( SD ) above the mean for normals was compared with that of those without such elevations . SETTING Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center , Denver , CO . PATIENTS One-hundred and fifty-two consecutive out patients , ages 65 to 99 , were screened . Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospect ively evaluated and treated with cobalamin . MAIN OUTCOME MEASURES Cobalamin , methylmalonic acid , homocysteine , complete blood counts , neurologic examination , and neuropsychological testing . RESULTS The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and /or homocysteine elevated to > 3 SD was 14.5 % of the screened out patients . A similar proportion of patients with low normal serum cobalamin levels ( between 201 and 300 pg/mL ) demonstrated elevated metabolites > OUTPUT: MAIN RESULTS From the two included studies ( Seal 2002 ; Fourniere 1997 ) of people with dementia and low serum vitamin B12 levels , there was no statistically significant evidence of treatment effect , vitamin B12 supplementation compared with placebo , on cognitive function . INPUT: BACKGROUND The st and ard treatment for cobalamin ( vitamin B(12 ) ) deficiency involves regular intramuscular cobalamin injection . It has been suggested that oral cobalamin therapy may be effective for treating patients who have food-cobalamin malabsorption . SUBJECTS AND METHODS We prospect ively studied 10 patients with cobalamin deficiency and well-established food-cobalamin malabsorption who received 3000 microg or 5000 microg of oral crystalline cyanocobalamin once a week for at least 3 months . Complete blood counts and serum cobalamin , homocysteine , and folate levels were determined at baseline and after 3 months of treatment . Patients were reexamined after 6 months . RESULTS After 3 months of treatment , all patients had increased hemoglobin levels ( mean increase , 1.9 g/dL ; 95 % confidence interval : 0.9 to 3.9 g/dL;P < 0.01 compared with baseline ) and decreased erythrocyte cell volume ( mean decrease , 7.8 fL ; 95 % confidence interval : 0.9 to 16.5 fL;P<0.001 ) . However , 2 patients had only minor , if any , responses . Serum cobalamin levels were increased in all 8 patients in whom it was measured . CONCLUSION Our findings suggest that moderate doses of crystalline cyanocobalamin given orally may be an effective treatment for food-cobalamin malabsorption AIMS To investigate the nasal absorption of hydroxocobalamin in 10 healthy elderly adults . METHODS In a cross-over study , blood sample s were collected before administration of the drug and after 10 , 20 , 30 , 40 , 60 , 120 , 180 and 240 min . The plasma cobalamin concentration was determined by competitive radioisotope binding technique . RESULTS The maximal plasma cobalamin concentration ( Cmax ) after nasal administration of 750 microg hydroxocobalamin was 1900 + /- 900 pmol l(-1 ) ( mean + /- s.d . ) . The maximal plasma cobalamin concentration was reached in 35 + /- 13 min ( t[max ] ) . The Cmax after nasal administration of 1500 microg hydroxocobalamin was 3500 + /- 2500 pmol l(-1 ) with a t(max ) of 28 + /- 16 min . Both the AUC(0,240 min ) and AUC(0,00 ) increased significantly with an increase of the dose from 750 microg to 1500 microg ( P = 0.037 and P = 0.028 , respectively ) . The nasal spray was well tolerated . No signs of irritation or local sensitivity were noted . CONCLUSIONS The nasal absorption of hydroxocobalamin in healthy elderly adults is rapid , high and well tolerated Because cobalamin deficiency is routinely treated with parenteral cobalamin , we investigated the efficacy of oral therapy . We r and omly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1 , 3 , 7 , 10 , 14 , 21 , 30 , 60 , and 90 or 2 mg orally on a daily basis for 120 days . Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin ( normal , 200 to 900 pg/mL ) methylmalonic acid ( normal , 73 to 271 nmol/L ) , and homocysteine ( normal , 5.1 to 13.9 micromol/L ) . Five patients were subsequently found to have folate deficiency , which left 18 evaluable patients in the oral group and 15 in the parenteral group . Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups . The mean pretreatment values for serum cobalamin , methylmalonic acid , and homocysteine were , respectively , 93 pg/mL , 3,850 nmol/L , and 37 . 2 micromol/L in the oral group and 95 pg/mL , 3,630 nmol/L , and 40.0 micromol/L in the parenteral therapy group . After 4 months of therapy , the respective mean values were 1,005 pg/mL , 169 nmol/L , and 10.6 micromol/L in the oral group and 325 pg/mL , 265 nmol/L , and 12.2 micromol/L in the parenteral group . The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant , with P < .0005 and P < .05 , respectively . In cobalamin deficiency , 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior BACKGROUND Cobalamin ( vitamin B12 ) deficiency , the most common cause of megaloblastic anemia , is treated with intramuscular ( IM ) cobalamin . It has been suggested by some investigators that oral ( p.o . ) cobalamin treatment may be as effective in the treatment of this condition , with the advantages of ease of administration and lower cost . OBJECTIVE This study assessed the effects and cost of p.o . versus i.m . cobalamin treatment OUTPUT:

The efficacy was particularly highlighted when looking at the marked improvement in serum vitamin B12 levels and hematological parameters , for example hemoglobin level , mean erythrocyte cell volume and reticulocyte count . Oral cobalamin treatment avoids the discomfort , inconvenience and cost of monthly injections . TAKE HOME MESSAGE Our experience and the present analysis support the use of oral cobalamin therapy in clinical practice

MS2_dynamic_1_shot13

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Objectives : Examining the effects of tracheal suctioning on cerebral hemodynamics of normotensive ventilated very low birth weight ( VLBW ) infants with normal cranial ultrasounds ; determining the factor(s ) influencing changes in mean cerebral blood flow velocity ( CBFv ) after suctioning . Methods : Seventy-three VLBW infants had continuous monitoring of mean arterial blood pressure ( MABP ) , PaCO2 , PaO2 and mean CBFv before , during , and after 202 suctioning sessions during the first week of life . Peak ( or nadir ) and relative changes of the four variables for 45 min after suctioning were calculated . Multiple linear regression was used to determine the factor(s ) influencing changes in mean CBFv after suctioning . Result : Birth weight was 928±244 g ; gestational age was 27.0±2.0 weeks . Mean CBFv increased to 31.0±26.4 % after suctioning and remained elevated for 25 min . PaCO2 was highly associated with mean CBFv ( P<0.001 ) , whereas MABP and PaO2 were not . Conclusion : We observed prolonged increases of mean CBFv following suctioning in ventilated VLBW infants that were previously unrecognized . This is concerning since disturbances of CBF may be associated with subsequent brain injury Abstract A numeric scoring system for the assessment of hypoxic ischaemic encephalopathy during the neonatal period was tested . The value of the score in predicting neurodevelopmental outcome at 1 y of age was assessed . Forty‐five infants who developed hypoxic ischaemic encephalopathy after birth were studied prospect ively . In addition to the hypoxic ischaemic encephalopathy score all but two infants had at least one cranial ultrasound examination . Thirty‐five infants were evaluated at 12 months of age by full neurological examination and the Griffiths Scales of Mental Development . Five infants were assessed at an earlier stage , four who died before 6 months of age and one infant who was hospitalized at the time of the 12 month assessment . Twenty‐three ( 58 % ) of the infants were normal and 17 ( 42 % ) were abnormal , 16 with cerebral palsy and one with developmental delay . The hypoxic ischaemic encephalopathy score was highly predictive for outcome . The best correlation with outcome was the peak score ; a peak score of 15 or higher had a positive predictive value of 92 % and a negative predictive value of 82 % for abnormal outcome , with a sensitivity and specificity of 71 % and 96 % , respectively . For the clinician working in areas where sophisticated technology is unavailable this scoring system will be useful for assessment of infants with hypoxic ischaemic encephalopathy and for prognosis of neurodevelopmental outcome The effect of oro-naso-pharyngeal suction at birth on pulmonary mechanics is described in a r and om assigned controlled study of 40 normal term vaginally born infants . Twenty cases had their oro-naso-pharynx suctioned immediately after birth ( S Group ) , whereas 20 were not suctioned in the neonatal period ( NS Group ) . A computerized pneumotachographic system ( MECVENT ) was used for the assessment of respiratory mechanics ( Dynamic Compliance ( C. Dyn . ) and Total Pulmonary Resistance ( R ) in inspiration and expiration at 10 , 30 and 120 minutes after birth . In both groups the C. Dyn increased during the study period whereas the R decreased , mainly in the initial 30 minutes . No significant differences were observed between S and NS groups for any of the parameters of respiratory mechanics . The results obtained in this study provide no physiological basis to recommend routine airway suction at birth in normal , term , vaginally born infants Adverse changes in cerebral hemodynamics during endotracheal suctioning have been reported in conventionally ventilated newborns , whereas observations on the effect of endotracheal suctioning during high-frequency ventilation have not been reported to date . The present study was design ed to investigate the effect of endotracheal suctioning on cerebral hemodynamics in high-frequency and conventionally ventilated infants . Changes in cerebral concentration of oxygenated ( cO(2)Hb ) and deoxygenated hemoglobin ( cHHb ) and oxidized cytochrome aa3 ( cCyt.aa3 ) were measured by noninvasive near-infrared spectroscopy . In an open prospect i ve study , 26 suctioning periods in 9 high-frequency and in 6 conventionally ventilated newborn infants were investigated . Heart rate , arterial oxygen saturation ( SaO(2 ) ) , mean blood pressure ( MABP ) , and transcutaneous carbon dio OUTPUT: The currently available evidence does not support or refute the benefits or harms of routine oro/nasopharyngeal suction over no suction . INPUT: In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias BACKGROUND AND OBJECTIVE : Late-onset sepsis frequently complicates prematurity , contributing to morbidity and mortality . Probiotics may reduce mortality and necrotizing enterocolitis ( NEC ) in preterm infants , with unclear effect on late-onset sepsis . This study aim ed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis . METHODS : A prospect i ve multicenter , double-blinded , placebo-controlled , r and omized trial compared daily administration of a probiotic combination ( Bifidobacterium infantis , Streptococcus thermophilus , and Bifidobacterium lactis , containing 1 × 109 total organisms ) with placebo ( maltodextrin ) in infants born before 32 completed weeks ’ gestation weighing < 1500 g. The primary outcome was at least 1 episode of definite late-onset sepsis . RESULTS : Between October 2007 and November 2011 , 1099 very preterm infants from Australia and New Zeal and were r and omized . Rates of definite late-onset sepsis ( 16.2 % ) , NEC of Bell stage 2 or more ( 4.4 % ) , and mortality ( 5.1 % ) were low in controls , with high breast milk feeding rates ( 96.9 % ) . No significant difference in definite late-onset sepsis or all-cause mortality was found , but this probiotic combination reduced NEC of Bell stage 2 or more ( 2.0 % versus 4.4 % ; relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 , P = .03 ; number needed to treat 43 , 95 % confidence interval 23 to 333 ) . CONCLUSIONS : The probiotics B infantis , S thermophilus , and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants , but not definite late-onset sepsis or mortality . Treatment with this combination of probiotics appears to be safe The value of prophylactic oral gentamicin sulfate therapy in the prevention of necrotizing enterocolitis ( NEC ) was evaluated in a group of 42 high-risk neonates over a four-month period in a r and omized , double-blind controlled trial . Twenty babies in the treatment group received 2.5 mg/kg of gentamicin sulfate every six hours for one week after birth , and 22 babies received dextrose- and -water placebo in an equivalently small volume . None of the 20 gentamicin-treated babies developed NEC . Four of the control babies did . Two of these babies died , and their diagnosis was pathologically confirmed . This difference in the incidence of NEC between the treatment and control group was significant at the .05 level . These results support the prophylactic use of orally given gentamicin for selected babies at high risk for NEC , particularly those born prematurely and those who have a history of perinatal asphyxia or umbilical artery catheterization or both . Continued surveillance for changes in antimicrobial sensitivity patterns is recommended Small premature infants are often hypochlorhydric , and frequently their stomachs are colonized by enteric , gram-negative bacteria . We tested a hypothesis that gastric pH affected the colonization of the stomach with enteric bacteria and that this colonization was causally related to the risk or severity of necrotizing enterocolitis . A prospect i ve , double-blind study was conducted that compared a group of infants supplemented with 0.01–0.02 ml of 1 N HCl/ml of milk to a group with a similar supplement of water . Gastric pH , gastric enteric bacteria counts , and the incidence and severity of necrotizing enterocolitis were monitored . The median gastric pH of the HCl-supplemented group was lower ( 3.0 ) than controls ( 4.0 ) throughout the study ( p < 0.001 ) . The gastric enteric bacterial colonization rate and the quantitative bacterial counts were strongly correlated with gastric pH over 4 ( p < 0.001 ) . Somatic growth rates in infants in the HCl-supplemented group were equal to , or exceeded , those in the control group . There was 1 case of necrotizing entero-colitis among the 34 infants in the HCl-supplemented group and 8 cases among the 34 in the control group ( p = 0.02 ) . It appears that acidifying the feedings of small premature infants to a pH low enough to inhibit bacterial proliferation in the stomach significantly lowers the risk of OUTPUT:

Based on the available trials , the evidence does not support the administration of oral immunoglobulin for the prevention of NEC . There are no r and omized controlled trials of oral IgA alone for the prevention of NEC

MS2_dynamic_1_shot14

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: Abstract : The aim of this placebo-controlled , r and omized , single-masked study was to establish the effects of a 10-week ambulatory exercise programme for osteoporotic patients on pain , use of analgesics , functional status , quality of life , balance and muscle strength . Fifty-three ambulatory postmenopausal women with at least one spinal crush fracture and pains within the last 3 years were r and omized for physiotherapeutic training twice a week for 10 weeks or no training . The training included general training of balance and muscle strength , with stabilization of the lumbar spine . The participants were tested at baseline , week 5 and week 10 with a balance test , muscle strength test and question naires on pain , use of analgesics , functional status and quality of life . Twelve weeks after the supervised training had finished ( week 22 ) they answered the same question naires . The study groups were comparable at baseline . The training group had a significant reduction in use of analgesics ( p= 0.02 ) and pain level ( p= 0.01 ) during the training period . Distribution of functional score improved ; the improvement was reduced at week 22 . Quality of life score improved significantly throughout the study ( p= 0.0008 ) , even after week 22 . Balance improved non-significantly ( p= 0.08 ) . Quadriceps muscle strength improved significantly after 5 weeks ( p= 0.04 ) . Back extensor muscle strength improved almost significantly ( p= 0.09 ) . In conclusion , this training programme for osteoporotic patients improved balance and level of daily function and decreased experience of pain and use of analgesics . Quality of life was improved even beyond the active training period BACKGROUND Physical activity has been related to enhanced bone mass and improved physical functioning and thus may reduce the risk for osteoporotic fracture . OBJECTIVE To determine whether higher levels of physical activity are related to lower incidence of hip , wrist , and vertebral fractures . DESIGN Prospect i ve cohort study . SETTING Four clinical centers in Baltimore , Maryl and ; Portl and , Oregon ; Minneapolis , Minnesota ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS 9704 nonblack women 65 years of age or older . MEASUREMENTS Physical activity was assessed by question naire at baseline . Hip and wrist fractures were followed for an average of 7.6 years . The incidence of vertebral fracture was determined morphometrically by using radiography at baseline and an average of 3.7 years later . RESULTS Higher levels of leisure time , sport activity , and household chores and fewer hours of sitting daily were associated with a significantly reduced relative risk for hip fracture after adjustment for age , dietary factors , falls at baseline , and functional and health status . Very active women ( fourth and fifth quintiles ) had a statistically significant 36 % reduction in hip fractures ( relative risk , 0.64 [ 95 % CI , 0.45 to 0.891 ) compared with the least active women ( lowest quintile ) . The intensity of physical activity was also related to fracture risk : Moderately to vigorously active women had statistically significant reductions of 42 % and 33 % in risk for hip and vertebral fractures , respectively , compared with inactive women . Total physical activity , hours of household chores per day , and hours of sitting per day were not significantly associated with wrist or vertebral fractures . CONCLUSIONS Among older community-dwelling women , physical activity is associated with a reduced risk for hip fracture but not wrist or vertebral fracture Physical exercise has a favorable impact on bones , but optimum training strategies are still under discussion . In this study , we compared the effect of slow and fast resistance exercises on various osteodensitometric parameters . Fifty-three postmenopausal women were r and omly assigned to a strength training ( ST ) or a power training group ( PT ) . Both groups carried out a progressive resistance training , a gymnastics session , and a home training over a period of 12 mo . During the resistance training , the ST group used slow and the PT group fast movements ; otherwise there were no training differences . All subjects were supplemented with Ca and vitamin D. At baseline and after 12 mo , bone mineral density ( BMD ) was measured at the lumbar spine , proximal femur , and distal forearm by dual-energy X-ray absorptiometry . We also measured anthropometric data and maximum static strength . Frequency and grade of pain were assessed by question naire . After 12 mo , significant between-group differences were observed for BMD at the lumbar spine ( P < 0.05 ) and the total hip ( P < 0.05 ) . Whereas the PT group maintained BMD at the spine ( + 0.7 + /- 2.1 % , not significant ) and the total hip ( 0.0 + /- 1.7 % , not significant ) , the ST group lost significantly at both sites ( spine : -0.9 + /- 1.9 % ; P < 0.05 ; total hip : -1.2 + /- 1.5 % ; P < 0.01 ) . No significant between-group differences were observed for anthropometric data , maximum strength , BMD of the forearm , or frequency and grade of pain . These findings suggest that power training is more effective than strength training in reducing bone loss in postmenopausal women Abstract Objectives To evaluate postoperative medical complications and the association between these complications and mortality at 30 days and one year after surgery for hip fracture and to examine the association between preoperative comorbidity and the risk of postoperative complications and mortality . Design Prospect i ve observational cohort study . Setting University teaching hospital . Participants 2448 consecutive patients admitted with an acute hip fracture over a four year period . We excluded 358 patients : all those aged < 60 ; those with periprosthetic fractures , pathological fractures , and fractures treated without surgery ; and patients who died before surg OUTPUT: Interventions with balance exercises reduced falls or fall-related fractures and improved balance in the majority of the studies . Muscle strengthening exercises were effective in improving lower extremity strength and back extensor strength ; however , not all RCT ’s reported positive effects . Bone strength was improved by weight-bearing aerobic exercise with or without muscle strengthening exercise when the duration of the intervention was at least a year . Conclusions Exercise can reduce falls , fall-related fractures , and several risk factors for falls in individuals with low BMD . Exercise interventions for patients with osteoporosis should include weight-bearing activities , balance exercise , and strengthening exercises to reduce fall and fracture risk INPUT: Abstract : The aim of this placebo-controlled , r and omized , single-masked study was to establish the effects of a 10-week ambulatory exercise programme for osteoporotic patients on pain , use of analgesics , functional status , quality of life , balance and muscle strength . Fifty-three ambulatory postmenopausal women with at least one spinal crush fracture and pains within the last 3 years were r and omized for physiotherapeutic training twice a week for 10 weeks or no training . The training included general training of balance and muscle strength , with stabilization of the lumbar spine . The participants were tested at baseline , week 5 and week 10 with a balance test , muscle strength test and question naires on pain , use of analgesics , functional status and quality of life . Twelve weeks after the supervised training had finished ( week 22 ) they answered the same question naires . The study groups were comparable at baseline . The training group had a significant reduction in use of analgesics ( p= 0.02 ) and pain level ( p= 0.01 ) during the training period . Distribution of functional score improved ; the improvement was reduced at week 22 . Quality of life score improved significantly throughout the study ( p= 0.0008 ) , even after week 22 . Balance improved non-significantly ( p= 0.08 ) . Quadriceps muscle strength improved significantly after 5 weeks ( p= 0.04 ) . Back extensor muscle strength improved almost significantly ( p= 0.09 ) . In conclusion , this training programme for osteoporotic patients improved balance and level of daily function and decreased experience of pain and use of analgesics . Quality of life was improved even beyond the active training period Introduction : Specific pharmacological treatment reduces the incidence of fractures significantly in patients with osteoporosis . Unfortunately , compliance with such therapy is low in clinical practice and is inversely related to educational level . We hypothesized that patients ' knowledge of osteoporosis may be increased by a group-based multidisciplinary education programme . Methods : Three hundred patients , aged 45—81 years , recently diagnosed with osteoporosis and started on specific treatment , were r and omized to either the " school ' ' or " control ' ' group . Teaching was performed by nurses , physiotherapists , dieticians , and doctors , and design ed to increase the patient 's empowerment . The patient 's knowledge of osteoporosis was tested at study entry and at 3 months using a vali date d question naire . Results : At study entry , no differences in age or score ( 22 ( 18—24 ) ( median ( 25—75 percentiles ) ) vs. 22 ( 18—24 ) ) were seen between the school and control groups . The change in knowledge during the study , however , differed significantly between the two groups ( p<0.001 ) . In the school group , the increase in knowledge score correlated inversely with the level of education ; that is , the lower the education level , the higher the gain in knowledge during the course ( Rho=-0.25 , p<0.01 ) . Conclusions : A group-based multidisciplinary education programme significantly increases patients ' knowledge of the disease OBJECTIVE To examine the effect of community-based nutrition education intervention on calcium intake and bone mass in Vietnamese postmenopausal women . DESIGN A controlled trial was conducted in two groups as intervention and control . The intervention group was given nutrition education during 18 months to improve calcium intake , while the control subjects had the usual diet . Calcium intake and bone mass were evaluated every 6 months . Bone mass was assessed by speed of sound ( SOS ) at calcaneus , referred to as quantitative ultrasound measurement . Anthropometric indices and serum parathyroid hormone ( PTH ) were determined at baseline and at the end of intervention . SETTING Two rural communes of Hai Duong province located in the Red River Delta in Vietnam . SUBJECTS A total of 140 women aged 55 - 65 years , who were more than 5 years postmenopausal and with low calcium intake ( < 400 mg/d ) , were recruited . After 18 months of intervention , 108 women completed the study . RESULTS Calcium intake in the intervention group had increased significantly ( P < 0.01 ) while it had no significant changes in controls . SOS values were not changed significantly in the intervention subjects while it decreased significantly by 0.5 % in the controls ( P < 0.01 ) . The intervention led to a decrease in serum PTH by 12 % ( P < 0.01 ) . In the controls , there was an increase in serum PTH by 32 % ( P < 0.001 ) . CONCLUSION Nutrition education intervention was effective in improving calcium intake and retarding bone loss in the studied subjects OBJECTIVE : To define the effects of therapeutic exercise on bone density and back complaints . METHODS : A r and omised controlled trial with parallel groups was conducted in an outpatient clinic , Medical School , University of Vienna . Ninety two sedentary post-menopausal women with back problems were r and omly allocated to either exercise ( groups 1 and 2 ) or control ( group 3 , no exercise , n = 31 ) ; the exercise group was retrospectively subdivided into compliant ( group 1 , n = 27 ) and not fully compliant patients ( group 2 , n = 34 ) . Regular , initially supervised therapeutic exercise aim ed at restoring biomechanical function was performed for four years . Bone density in the forearm was measured by single photon absorptiometry at entry and after four years ; subjective back complaints were documented . RESULTS : A significant decrease in bone density was observed in groups 2 and 3 ; no change was noted in group 1 ; back complaints decreased in group 1 only . CONCLUSIONS : Sedentary postmenopausal women may benefit from regular long term therapeutic exercise in terms of subjective back complaints OUTPUT:

Collectively , these studies provided some evidence to show that interventions by healthcare professionals improved the QOL medication compliance and calcium intake of patients but its effects on BMD , medication persistence , knowledge , and other lifestyle modifications were less conclusive .

MS2_dynamic_1_shot15

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** INPUT: Pilot studies for phase III trials - which are comparative r and omized trials design ed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas . Also commonly know as " feasibility " or " vanguard " studies , they are design ed to assess the safety of treatment or interventions ; to assess recruitment potential ; to assess the feasibility of international collaboration or coordination for multicentre trials ; to increase clinical experience with the study medication or intervention for the phase III trials . They are the best way to assess feasibility of a large , expensive full-scale study , and in fact are an almost essential pre-requisite . Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies . The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including : 1 ) the general reasons for conducting a pilot study ; 2 ) the relationships between pilot studies , proof-of-concept studies , and adaptive design s ; 3 ) the challenges of and misconceptions about pilot studies ; 4 ) the criteria for evaluating the success of a pilot study ; 5 ) frequently asked questions about pilot studies ; 7 ) some ethical aspects related to pilot studies ; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format OBJECTIVE To test the feasibility , acceptability , and potential efficacy of after-school dance classes and a family-based intervention to reduce television viewing , thereby reducing weight gain , among African-American girls . DESIGN Twelve-week , 2-arm parallel group , r and omized controlled trial . SETTING Low-income neighborhoods . PARTICIPANTS Sixty-one 8 - 10-year-old African-American girls and their parents/guardians . INTERVENTIONS The treatment intervention consisted of after-school dance classes at 3 community centers , and a 5-lesson intervention , delivered in participants ' homes , and design ed to reduce television , videotape , and video game use . The active control intervention consisted of disseminating newsletters and delivering health education lectures . MAIN OUTCOME MEASURES Implementation and process measures , body mass index , waist circumference , physical activity measured by accelerometry , self-reported media use , and meals eaten with TV . RESULTS Recruitment and retention goals were exceeded . High rates of participation were achieved for assessment s and intervention activities , except where transportation was lacking . All interventions received high satisfaction ratings . At follow up , girls in the treatment group , as compared to the control group , exhibited trends toward lower body mass index ( adjusted difference = -.32 kg/m2 , 95 % confidence interval [ CI ] -.77 , .12 ; Cohen 's d = .38 st and ard deviation units ) and waist circumference ( adjusted difference = -.63 cm , 95 % CI -1.92 , .67 ; d = .25 ) ; increased after-school physical activity ( adjusted difference = 55.1 counts/minute , 95 % CI -115.6 , 225.8 ; d = .21 ) ; and reduced television , videotape , and video game use ( adjusted difference = -4.96 hours/week , 95 % CI -11.41 , 1.49 ; d = .40 ) . The treatment group reported significantly reduced household television viewing ( d = .73 , P = .007 ) and fewer dinners eaten while watching TV ( adjusted difference = -1.60 meals/week , 95 % CI -2.99 , -.21 ; d = .59 ; P = .03 ) . Treatment group girls also reported less concern about weight ( d = .60 ; P = .03 ) , and a trend toward improved school grade s ( d = .51 ; P = .07 ) . CONCLUSIONS This study confirmed the feasibility , acceptability , and potential efficacy of using dance classes and a family-based intervention to reduce television viewing , thereby reducing weight gain , in African-American girls To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , OUTPUT: Pre-emptive avoidance of RGBs during the initial testing of an intervention may diminish the voltage drop between pilot and larger efficacy/effectiveness trials and enhance the odds of successful translation INPUT: Pilot studies for phase III trials - which are comparative r and omized trials design ed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas . Also commonly know as " feasibility " or " vanguard " studies , they are design ed to assess the safety of treatment or interventions ; to assess recruitment potential ; to assess the feasibility of international collaboration or coordination for multicentre trials ; to increase clinical experience with the study medication or intervention for the phase III trials . They are the best way to assess feasibility of a large , expensive full-scale study , and in fact are an almost essential pre-requisite . Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies . The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including : 1 ) the general reasons for conducting a pilot study ; 2 ) the relationships between pilot studies , proof-of-concept studies , and adaptive design s ; 3 ) the challenges of and misconceptions about pilot studies ; 4 ) the criteria for evaluating the success of a pilot study ; 5 ) frequently asked questions about pilot studies ; 7 ) some ethical aspects related to pilot studies ; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format Feasibility and pilot studies play an important role in the preliminary planning of a proposed full-size r and omized clinical trial ( RCT ) . In essence , feasibility studies are used to help develop trial interventions or outcome measures , whereas pilot studies replicate , in miniature , a planned full-size RCT . However , the terms used for these preliminary studies are sometimes considered synonymous , and in practice may overlap considerably or be combined . The important issue is not the distinction between these : the important distinction is between such preliminary studies and a proper RCT . J Orthop Sports Phys Ther 2014;44(8):555–558 . Many factors can affect the successful implementation and validity of intervention studies . A primary purpose of feasibility and pilot studies is to assess the potential for successful implementation of the proposed main intervention studies and to reduce threats to the validity of these studies . This article describes a typology to guide the aims of feasibility and pilot studies design ed to support the development of r and omized controlled trials and provides an example of the studies underlying the development of one rehabilitation trial . The purpose of most feasibility and pilot studies should be to describe information and evidence related to the successful implementation and validity of a planned main trial . Null hypothesis significance testing is not appropriate for these studies unless the sample size is properly powered . The primary tests of the intervention effectiveness hypotheses should occur in the main study , not in the studies that are serving as feasibility or pilot studies BACKGROUND People with Multiple Sclerosis ( PwMS ) are less physically active than the general population and pragmatic approaches design ed to equip them with the skills and confidence to participate in long-term physical activity are required . OBJECTIVE The objective of this study was to determine the feasibility of a pragmatic exercise intervention in PwMS . METHODS A voluntary sample of 30 PwMS ( male n = 4 , female n = 26 ; mean age = 40 years ; range = 24 - 49 years ) , with mild to moderate disability ( EDSS ≤ 5.5 ) , were recruited from eligible participants attending outpatient clinics . A total of 28 participants were r and omised to a 10 week pragmatic exercise intervention ( 2 × supervised and 1 × home-based session per week ) or usual care . Clinical , functional and quality of life ( MSQoL-54 ) outcomes were assessed at baseline , immediately and 3 months after the intervention . RESULTS Attrition was low ( 2 participants lost to immediate follow-up and 4 participants lost to 3 month follow-up ) , with high compliance rates ( > 75 % of all sessions ) . The intervention group achieved progression of exercise volume ( 24.3 ± 7.0 to 30.9 ± 5.5 min per session ) , intensity ( 60.4 ± 8.8 to 67.7 ± 6.9 % HR max ) and training impulse ( min × average HR = training impulse/load [ arbitrary units ; AU ] ) ( 2600 ± 1105 to 3210 ± 1269AU ) during the intervention , whilst significantly increasing(P = 0.050 ) their physical composite score ( MSQOL-54 ) at 10 weeks and readiness to exercise ( P = 0.003 ) at 3 months compared with usual care . CONCLUSION This pragmatic intervention was feasible for PwMS , but further research is needed to assess its long-term impact on physical activity behaviour Background The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame . Despite an increase in research into the benefits of exercise in people with multiple sclerosis ( PwMS ) , no trial has reported detailed data on effective recruitment strategies for large-scale r and omised controlled trials . The main purpose of this report is to provide a detailed outline of recruitment strategies , rates and estimated costs in the Exercise Intervention for Multiple Sclerosis ( ExIMS ) trial to identify best practice s for future trials involving multiple sclerosis ( MS ) patient recruitment . Methods The ExIMS research ers recruited 120 PwMS to participate in a 12-week exercise intervention . Participants were r and omly allocated to either exercise or usual-care control groups . Participants were sedentary , aged 18–65 years and had Exp and ed Disability Status Scale scores of 1.0–6.5 . Recruitment strategies included attendance at MS outpatient clinics , consultant mail-out and trial awareness-raising activities . Results A total of 120 participants were recruited over the course of 34 months . To achieve this target , 369 potentially eligible and interested participants were identified . A total of 60 % of participants OUTPUT:

Our case study successfully enabled us to address the four feasibility metrics , and we provide new information on management feasibility ( i.e. estimate data completeness and estimate data entry ) and scientific outcomes feasibility ( i.e. determining data collection material s appropriateness ) . Conclusion Our review highlights the existing research and provides a case study which assesses important metrics of study feasibility .