nils-herrmann/clean_scirepeval huggingface dataset:
Estimation of the area under the concentration-versus-time curve of carboplatin following irinotecan using a limited sampling model

The aim of this study was to develop limited sampling models for estimating the area under the concentration-versus-time curve (AUC) of carboplatin.  Based on pharmacokinetic analyses of 14 patients who received 300 mg · m2 of carboplatin over a 90-min infusion following irinotecan, we developed limited sampling models with stepwise multiple linear regression analysis. We validated these models to be unbiased and precise using pharmacokinetic data of a second group of 14 patients. We also compared the observed and the predicted AUC in the patients using Calvert's formula with the patients' renal function.  We developed the following models: AUC (mg · ml−1 · min) = 0.784 × C4 + 1.30 (r 2 = 0.930) and AUC = 0.100 × C0.25 + 0.597 × C4 + 0.140 (r 2 = 0.992), where C0.25 and C4 denote unbound plasma concentrations (μg · ml−1) of carboplatin at 0.25 h and 4 h after the end of infusion, respectively. These models were validated to be unbiased and precise: a mean prediction error (MPE) with standard deviation (SD) = 2.41 (9.45)% and a root mean squared error (RMSE) = 9.42% for the one-sample model, and MPE with (SD) = 1.22 (5.56)% and RMSE = 5.49% for the two-sample model. We also calculated predicted AUC in the patients using Calvert's formula: MPE with (SD) =−5.87 (21.5)% and RMSE = 21.5%.  These estimations were, as expected, more accurate than the prediction using Calvert's formula based on patients' renal function. The result of this study confirmed the idea that the pharmacokinetic parameters derived from limited sampling models would be more suitable for pharmacokinetic analysis of carboplatin than those obtained using Calvert's formula.
Montelukast improves regional air-trapping due to small airways obstruction in asthma.

Quantitative image analysis of high-resolution computed tomography (HRCT) performed at residual volume, before and after methacholine, is a sensitive method of detecting small airways involvement in asthma and response to therapy targeted to the small airways. Since an oral anti-leukotriene reaches the small airways via the circulation, the present authors hypothesised that treatment with montelukast would lead to improved small airway patency. A double-blind crossover study compared the effect of montelukast versus placebo for 4 weeks in 16 mild-to-moderate steroid-naïve asthmatics. Small airways function was evaluated by HRCT at residual volume before and after methacholine to assess regional air-trapping and airways hyperresponsiveness, as well as by physiological studies of small airways. Montelukast treatment resulted in significantly less regional air-trapping on HRCT on the pre-methacholine images when compared with placebo, as well as improvement in total quality of life scores and symptom sub-scores. However, montelukast treatment had no effect on increases in regional air-trapping on HRCT in response to methacholine. No differences were noted in global measures of small airways physiology between placebo and montelukast. In conclusion, distal airways disease improves in asthmatic subjects treated with montelukast. This improvement can be detected with high-resolution computed tomography, but not with conventional physiological studies.
Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect.



The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included.



To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.
Increased protein turnover and proteolysis is an early and primary feature of short-term experimental hyperthyroidism in healthy women.

Hyperthyroidism increases energy expenditure, glucose turnover, lipolysis, and protein breakdown.



Our objective was to test whether increased protein breakdown occurs independently of other catabolic effects in mild experimental hyperthyroidism.



We conducted a single-blind, randomized, placebo-controlled, crossover study. Protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique ([(15)N]phenylalanine and [(2)H(4)]tyrosine). All subjects underwent a 3-h study in the basal state followed by a 3-h euglycemic clamp study.



The study took place at a university clinical research unit.



Eight healthy women (24-46 yr old) participated.



Intervention included 6 d thyroid hormone (T(4) 50 microg and T(3) 0.67 microg/kg.d) or placebo administration.



Thyroid hormone administration led to mild T(3) hyperthyroidism with more than a doubling of T(3) levels and suppression of TSH. Energy expenditure and body composition was unchanged. Glucose infusion rates, forearm glucose uptake, and levels of lipid intermediates were also alike. Basal whole-body phenylalanine flux and tyrosine flux (reflecting whole-body protein breakdown) were increased (P < 0.05) as were whole-body protein synthesis rate (P = 0.05). Basal forearm rate of appearance and disappearance for phenylalanine (reflecting muscle protein breakdown and synthesis) were similar.



Mild short-term experimental hyperthyroidism increases whole-body protein turnover and breakdown before any measurable changes in energy expenditure or glucose and fat metabolism, suggesting that amino acid and protein metabolism is an early and primary target for thyroid hormone action in humans.
Validation of a Japanese version of the Stanford Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis.

To develop and validate a self-administered instrument for measuring functional status in Japanese-speaking rheumatoid arthritis patients.



We translated the Stanford Health Assessment Questionnaire (HAQ) into Japanese (original HAQ), and then made a tentative Japanese version of the HAQ (J-HAQ) with culturally appropriate modifications of the arising, eating, and reach category questions. The questionnaire was then administered to 3,763 RA patients (82.6% female; mean age 58.0 years; mean onset age 47.4 years; mean disease duration 10.5 years).



This instrument showed excellent internal reliability (Cronbach's alpha = 0.927), with a mean interitem correlation of 0.60. For the arising category question, the J-HAQ asks about arising from a futon in addition to a bed because futons are still common in Japanese culture. Arising from a futon is generally more difficult for disabled individuals than is arising from a bed, so the arising score was higher in the J-HAQ (mean score 0.82) than in the original HAQ (0.48). The average scores for the eating and reach categories were virtually identical for the original HAQ and the J-HAQ, with correlation coefficients of 0.979 and 0.926, respectively. Thus, the overall disability index (average of the scores for all functional areas) was higher in the J-HAQ (0.81) than in the original HAQ (0.76), although the correlation coefficient was high (0.993). The test-retest reliability value (0.92), studied at a 1-week interval, revealed identical disability index scores measured on the 2 occasions.



The final version of the J-HAQ is a valid and reliable instrument for measuring functional status in Japanese-speaking RA patients.
Long-term functional outcome in adult prison inmates with ADHD receiving OROS-methylphenidate

In a recent randomized, double-blind, placebo-controlled trial, we established a robust efficacy (Cohen’s d = 2.17) of osmotic release oral system-methylphenidate (OROS-methylphenidate) delivered 72 mg daily for 5 weeks versus placebo on attention deficit hyperactivity disorder (ADHD) symptoms, global severity and global functioning in 30 adult male prison inmates with ADHD and coexisting disorders. Outcomes continued to improve during the subsequent 47-week open-label extension with OROS-methylphenidate delivered at a flexible daily dosage of up to 1.3 mg/kg body weight. In the present study, we evaluated long-term effectiveness and maintenance of improvement over the cumulated 52-week trial on cognition, motor activity, institutional behaviour and quality of life. Post hoc, we explored the associations between investigators’ and self-ratings of ADHD symptoms and between ratings of symptoms and functioning, respectively. Outcomes, calculated by repeated measures ANOVA, improved from baseline until week 16, with maintenance or further improvement until week 52. Both verbal and visuospatial working memory, and abstract verbal reasoning improved significantly over time, as well as several cognition-related measures and motor activity. No substance abuse was detected and a majority of participants took part in psychosocial treatment programmes. The quality of life domains of Learning, and Goals and values improved over time; the latter domain was at open-label endpoint significantly related to improvements in attention. Investigators’ and self-ratings of ADHD symptoms, as well as global symptom severity related most significantly to global functioning at week 52. Finally, investigators’ and self-ratings of ADHD symptoms associated significantly at baseline with increasing convergence over time.
What determines the self-rated health of older individuals with stroke compared to other older individuals? A cross-sectional analysis of the Medical Research Council Cognitive Function and Aging Study

Poor self-rated health has been associated with poorer objective health outcomes across a range of conditions including stroke. Identification of factors associated with poor self-rated health in stroke survivors has received little attention compared to that in other older individuals. This study identifies determinants of self-rated health in older individuals with or without a history of stroke participating in the population-representative MRC Cognitive Function and Aging Study (MRC CFAS).



The MRC CFAS is a multicentred longitudinal survey of a population representative sample of people in their 65th year and older at baseline. Baseline interview included questions about functional disability, psychiatric history, independent living status, social interactions, and cognitive function. Multiple logistic regression was used to determine associations between demographic, physical, cognitive, psychological and social factors with poor self-rated health among those with and without stroke.



After excluding those with impaired cognitive function, 776 individuals out of 11,957 reported a stroke. Factors associated with self-rated health were similar between those with or without a stroke in older individuals. Poorer self-rated health in those who had suffered a stroke was associated predominantly with the presence of comorbidity with diabetes (OR 3.5; 95% CI 1.5-8.1) and not "getting out and about" (OR 2.6; 95% CI 1.7-4.1) even after adjustment for disability levels and for depression. In those without a stroke the most important determinants were disability (OR 3.9; 95% CI 3.2-4.8) and not "getting out and about" (OR 2.9; 95% CI 2.5-3.3). The presence of disability was less strongly associated with poor self-rated health in those with a history of stroke than those without due to a substantially higher reporting of poor self-rated health in the non-disabled stroke group than the non-disabled stroke-free group, while those with disabilities reported poor self-rated health irrespective of stroke status.



Self-rated health is determined by a range of psychological and social factors in addition to disability in older patients with stroke. Addressing social integration and mobility out of the home is an important element of rehabilitation for older people with stroke as well as those without.
Validation of the MDRF-Indian Diabetes Risk Score (IDRS) in another south Indian population through the Boloor Diabetes Study (BDS).

To validate the MDRF-Indian Diabetes Risk Score (IDRS) in a south Indian population in coastal Karnataka.



The study was conducted at Boloor locality in Mangalore on adults aged 20 years or more. The study group comprised 551 participants (68.9% response rate). The OGTT was performed using 75 gms of glucose. The MDRF-IDRS was calculated using age, family history of diabetes, physical activity and waist measurement. ROC curves were constructed to identify the optimum value (> or = 60%) of IDRS for determining diabetes as diagnosed using WHO consulting group criteria.



We found that 71 of the study individuals were known diabetic subjects (KD) while 45 subjects were diagnosed to have newly diagnosed diabetes (NDD). An IDRS score of > or =60 had the best sensitivity (62.2%) and specificity of (73.7%) for detecting undiagnosed diabetes in this community.



Our study confirms and validates the MDRF-IDRS as being a valid simple and reliable screening tool to identify undiagnosed diabetes in the community. The MDRF-IDRS score > or =60 had the highest sensitivity and specificity to identify undiagnosed diabetes.
No-Needle, Single-Visit Adult Male Circumcision with Unicirc: A Multi-Centre Field Trial

Voluntary medical male circumcision (VMMC) is a priority HIV preventive intervention. Current adult circumcision methods need improvement.



Field trial in 3 primary care centres. Minimally invasive VMMC using the Unicirc instrument following topical lidocaine/prilocaine anesthetic. Men were followed up at 1 and 4 weeks.



We circumcised 110 healthy volunteers. Two men complained of transient burning pain during circumcision, but none required injectable anaesthesia. Median blood loss was 1ml and median procedure time was 9.0 min. There were 7 (6.3%) moderate complications (5 (4.5%) post-operative bleeds requiring suture and 2 (1.8%) post-operative infections) affecting 7 men. No men experienced significant wound dehiscence. 90.4% of men were fully healed at 4 weeks of follow-up and all were highly satisfied.



Use of topical anaesthesia obviates the need for injectable anesthetic and makes the Unicirc procedure nearly painless. Unicirc is rapid, easy to learn, heals by primary intention with excellent cosmetic results, obviates the need for a return visit for device removal, and is potentially cheaper and safer than other methods. Use of this method will greatly facilitate scale-up of mass circumcision programs.
Efficacy of telaprevir-based therapy in stable liver transplant patients with chronic genotype 1 hepatitis C.

The REPLACE study (NCT01571583) investigated telaprevir-based triple therapy in patients who have recurrent genotype 1 hepatitis C virus (HCV) infection following liver transplantation and are on a stable immunosuppressant regimen of tacrolimus or cyclosporin A. Patients received telaprevir 750 mg 8-hourly with pegylated interferon 180 ?g weekly and ribavirin 600 mg daily, followed by a further 36 weeks of pegylated interferon and ribavirin alone and 24 weeks of follow-up. Efficacy (sustained virological response [SVR] 12 weeks after last planned study dose), safety and tolerability of telaprevir throughout the study were assessed. Pharmacokinetics of telaprevir, tacrolimus and cyclosporin A were also examined.



In total, 74 patients were recruited. Overall, 72% (53/74; 95% CI: 59.9 to 81.5) of patients achieved SVR at 12 weeks following completion of treatment. Anticipated increases in plasma concentrations of tacrolimus and cyclosporin A occurred during telaprevir treatment and were successfully managed through immunosuppressant dose reduction and, for tacrolimus, reduced dosing frequency. Safety and tolerability of telaprevir-based triple therapy were generally comparable with previous data in non-transplant patients, although rates of reported anemia (55% [41/74]) were higher. Elevated plasma creatinine (46% [34/74]) was observed during REPLACE - consistent with the post-liver transplant population and the co-administered immunosuppressants.



Telaprevir-based triple therapy in patients with recurrent genotype 1 HCV infection following liver transplantation produced high rates of SVR. Therapeutic concentrations of immunosuppressants were maintained successfully through dose modification during telaprevir treatment.
A Multicenter Retrospective Review of Prone Position Ventilation (PPV) in Treatment of Severe Human H7N9 Avian Flu

Patients with H7N9 avian flu concurrent with severe acute respiratory distress syndrome (ARDS) usually have a poor clinical outcome. Prone position ventilation (PPV) has been shown to improve the prognosis of patients with severe ARDS. This study explored the effects of PPV on the respiratory and circulatory mechanics of H7N9-infected patients with severe ARDS.



Individuals admitted to four hospitals designated for H7N9 patients in Guangdong province were treated with PPV, and their clinical data were recorded before and after receiving PPV.



Six of 20 critically ill patients in the ICU received PPV. After treatment with 35 PPV sessions, the oxygenation index (OI) values of the six patients when measured post-PPV and post-supine position ventilation (SPV) were significantly higher than those measured pre-PPV (P < 0.05).The six patients showed no significant differences in their values for respiratory rate (RR), peak inspiratory pressure (PIP), tidal volume (TV) or arterial partial pressure of carbon dioxide (PaCO2) when compared pre-PPV, post-PPV, and post-SPV. Additionally, there were no significant differences in the mean values for arterial pressure (MAP), cardiac index (CI), central venous pressure (CVP), heart rate (HR), lactic acid (LAC) levels or the doses of norepinephrine (NE) administered when compared pre-PPV, post-PPV, and post-SPV.



PPV provided improved oxygenation that was sustained after returning to a supine position, and resulted in decreased carbon dioxide retention. PPV can thus serve as an alternative lung protective ventilation strategy for use in patients with H7N9 avian flu concurrent with severe ARDS.
Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage.

Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH.



In this randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or rFVIIa (10, 20, 40, 80, 120, or 160 microg/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios.



Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11%). Six AEs were considered possibly treatment-related, including rash, vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis (placebo and 20-microg/kg groups). No myocardial ischemia, consumption coagulopathy, or dose-related increase in edema:ICH volume occurred.



This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.
The efficacy of coblation nucleoplasty for protrusion of lumbar intervertebral disc at a two-year follow-up

The purpose of this study was to evaluate longer-term efficacy over a two-year follow-up of coblation nucleoplasty treatment for protruded lumbar intervertebral disc. Forty-two cases of protruded lumbar intervertebral disc treated by coblation nucleoplasty followed-up for two years were analysed. Relief of low back pain, leg pain and numbness after the operation were assessed by visual analogue pain scale (VAS). Function of lower limb and daily living of patients were evaluated by the Oswestry Disability Index (ODI). Operations were performed successfully in all cases. Three patients had recurrence within a week of the procedure. Evaluation of the 42 patients demonstrated significant improvement rate of VAS: defined as 66.2% in back pain, 68.1% in leg pain, and 85.7% in numbness at one-week after the operation; 53.2%, 58.4%, 81.0% at one-year; and 45.5%, 50.7%, 75.0% at two-year follow-up. One week after the operation, obvious amelioration occurred in all the patients, but the tendency decreased. Before operation, the mean value of ODI was 68.2 ± 10.9%. The value at one week was 28.6 ± 8.2%; one-year at 35.8 ± 6.5%; and two-years at 39.4 ± 5.8%. Coblation nucleoplasty may have satisfactory clinical outcomes for treatment of protruded lumbar intervertebral disc for as long as two-year follow-up, but longer-term benefit still needs verification.