nils-herrmann/clean_scirepeval huggingface dataset:
Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial

The optimum dose of key antiretroviral drugs is often overlooked during product development. The ENCORE1 study compared the efficacy and safety of reduced dose efavirenz with standard dose efavirenz in combination with tenofovir and emtricitabine as first-line treatment for HIV infection. An effective and safe reduced dose could yield meaningful cost savings.



ENCORE1 is a continuing non-inferiority trial in HIV-1-infected antiretroviral-naive adults in 38 clinical sites in 13 countries. Participants (plasma HIV-RNA >1000 log10 copies per mL, CD4 T-cell count 50-500 cells per μL) were randomly assigned by a computer-generated sequence with a blocking factor of four (stratified by clinical site and by screening viral load) to receive tenofovir plus emtricitabine with either a reduced daily dose (400 mg) or a standard dose (600 mg) of efavirenz. Participants, physicians, and all other trial staff were masked to treatment group. The primary endpoint was the difference in proportions of participants with plasma HIV-RNA of less than 200 copies per mL at 48 weeks. Treatment groups were regarded as non-inferior if the lower limit of the 95% CI for the difference in viral load was less than -10% by modified intention-to-treat analysis. Adverse events were summarised by treatment. 
The modified intention-to-treat analysis consisted of 630 patients (efavirenz 400=321; efavirenz 600=309). 32% were women; 37% were African, 33% were Asian, and 30% were white. The mean baseline CD4 cell count was 273 cells per μL (SD 99) and median plasma HIV-RNA was 4·75 log10 copies per mL (IQR 0·88). The proportion of participants with a viral load below 200 copies per mL at week 48 was 94·1% for efavirenz 400 mg and 92·2% for 600 mg (difference 1·85%, 95% CI -2·1 to 5·79). CD4 T-cell counts at week 48 were significantly higher for the 400 mg group than for the 600 mg group (mean difference 25 cells per μL, 95% CI 6-44; p=0·01). We recorded no difference in grade or number of patients reporting adverse events (efavirenz 400=89·1%, efavirenz 600=88·4%; difference 0·75%, 95% CI -4·19 to 5·69; p=0·77). Study drug-related adverse events were significantly more frequent in the 600 mg group than in the 400 mg group (146% [47] vs 118 ), difference -10·5%, 95% CI -18·2 to -2·8; p=0·01) and significantly fewer patients with these events stopped treatment (400 mg=6 [2%], 600 mg=18 [6%], difference -3·96%, 95% CI -6·96 to -0·95; p=0·01).



Our findings suggest that a reduced dose of 400 mg efavirenz is non-inferior to the standard dose of 600 mg, when combined with tenofovir and emtricitabine during 48 weeks in ART-naive adults with HIV-1 infection. Adverse events related to the study drug were more frequent with 600 mg efavirenz than with 400 mg. Lower dose efavirenz should be recommended as part of routine care.



Bill & Melinda Gates Foundation, University of New South Wales.
Health-related quality of life and all-cause mortality in patients with diabetes on dialysis

This study tests the hypotheses that health-related quality of life (HRQOL) in prevalent dialysis patients with diabetes is lower than in dialysis patients without diabetes, and is at least as poor as diabetic patients with another severe complication, i.e. foot ulcers. This study also explores the mortality risk associated with diabetes in dialysis patients.



HRQOL was assessed using the Short Form-36 Health Survey (SF-36), in a cross-sectional study of 301 prevalent dialysis patients (26% with diabetes), and compared with diabetic patients not on dialysis (n = 221), diabetic patients with foot ulcers (n = 127), and a sample of the general population (n = 5903). Mortality risk was assessed using a Kaplan-Meier plot and Cox proportional hazards analysis.



Self-assessed vitality, general and mental health, and physical function were significantly lower in dialysis patients with diabetes than in those without. Vitality (p = 0.011) and general health (p <0.001) was impaired in diabetic patients receiving dialysis compared to diabetic patients with foot ulcers, but other subscales did not differ. Diabetes was a significant predictor for mortality in dialysis patients, with a hazard ratio (HR) of 1.6 (95% CI 1.0-2.5) after adjustment for age, dialysis vintage and coronary artery disease. Mental aspects of HRQOL were an independent predictor of mortality in diabetic patients receiving dialysis after adjusting for age and dialysis vintage (HR 2.2, 95% CI 1.0-5.0).



Physical aspects of HRQOL were perceived very low in dialysis patients with diabetes, and lower than in other dialysis patients and diabetic patients without dialysis. Mental aspects predicted mortality in dialysis patients with diabetes. Increased awareness and measures to assist physical function impairment may be particularly important in diabetes patients on dialysis.
Introduction of hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders.

Therapeutic hypothermia was introduced in the Netherlands and Flanders, Belgium, in 2008. Since then, an increasing number of patients has been treated - up to 166 in 2010. Complications and outcome were registered in an online database.



The aim of this study was to analyse complications and outcome after implementation.



Data were retrieved from an online database to which all centres had contributed.



In 3 years, 332 patients were treated. Excluding 24 patients with congenital abnormalities or metabolic disorders, mortality was 31.8%. Of the 210 survivors without congenital malformations, 21 had cerebral palsy, another 19 a developmental delay of more than 3 months at the age of at least 24 months, and 2 had severe hearing loss. The total adverse outcome, combining death and adverse neurodevelopment, in 308 patients without congenital malformations is 45.5%, which is similar to that of the large trials.



The introduction of therapeutic hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders has been rapid and successful, with results similar to findings in the randomised controlled trials.
Cytology in the diagnosis of cervical cancer in symptomatic young women: a retrospective review

Cervical cancer in young women presents a diagnostic challenge because gynaecological symptoms are common but underlying disease is rare.



To explore the potential for using cytology as a diagnostic aid for cervical cancer in young women.



Retrospective review of primary care records and cytology data from the national cervical screening database and national audit of cervical cancers.



Four datasets of women aged 20-29 years in England were examined: primary care records and national screening data from an in-depth study of cervical cancers; cytology from the national audit of cervical cancers; whole-population cytology from the national screening database; and general-population primary care records from the Clinical Practice Research Datalink. The authors explored the sensitivity and positive predictive value (PPV) of symptomatic cytology (earliest <12 months before diagnosis) to cervical cancer.



The estimated prevalence of cervical cancer among symptomatic women was between 0.4% and 0.9%. The sensitivity of moderate dyskaryosis (high-grade squamous intraepithelial lesion [HSIL]) or worse in women aged 20-29 years was 90.9% to 96.2% across datasets, regardless of symptom status. The PPV was estimated to be between 10.0% and 30.0%. For women aged 20-24 years, the PPV of '?invasive squamous carcinoma' was 25.4%, and 2.0% for severe or worse cytology.



Cytology has value beyond screening, and could be used as a diagnostic aid for earlier detection of cervical cancer in young women with gynaecological symptoms by ruling in urgent referral.
Early onset of treatment effects with oral risperidone

The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia.



In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14.



Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore.



Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration.
Impaired sexual activity in young ischaemic stroke patients: an observational study.

The present study sought to determine the impact of stroke on sexual function and well-being in a cohort of young ischaemic stroke patients and identify factors associated with impairment.



Over a 2-year period, all patients aged 60 or under with ischaemic stroke or transient ischaemic attack (n = 156) were included. Information on sexual function and well-being was obtained by means of a paper questionnaire mailed to participants 1 year after their stroke. Impaired sexual activity (ISA) was defined as a decline in sexual function and/or satisfaction. Psychological well-being was evaluated on the Hospital Anxiety and Depression Scale (HADS).



The response rate was 67% (n = 104). Thirty of these responders (29%) reported ISA. Patients with ISA had a higher HADS score (19.7 vs. 11.2 in patients with no impairment; P < 0.001), anxiety score (10.0 vs. 6.3; P < 0.001) and depression score (8.7 vs. 4.8; P < 0.001) and were more likely to have left brain lesions (70% vs. 30%; P < 0.001) and use angiotensin-converting enzyme (ACE) inhibitors (73% vs. 31%; P < 0.001) and diuretics (50% vs. 19%; P = 0.003). In a stepwise logistic regression, depression (odds ratio 9.1, 95% confidence interval 2.45-33.46; P = 0.001) and ACE inhibitor use (odds ratio 6.0, 95% confidence interval 2.11-17.28; P = 0.001) were associated with ISA.



Impaired sexual activity was reported by almost one-third of younger patients 1 year after ischaemic stroke. Factors associated with post-stroke ISA may include specific medications and depression rather than the characteristics of the stroke per se.
Influence of estrogen therapy on calcium, phosphorus, and other regulatory hormones in postmenopausal women: the MESA study.

Estrogen therapy (ET) is associated with lower serum calcium and phosphorus concentrations and is known to increase bone mineral density (BMD). Other biomarkers of mineral metabolism may help understand the biological basis of these actions.



We studied 2767 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis, 862 (31%) of whom were using ET. We measured serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D, 24,25-dihydoxyvitamin D, and fibroblast growth factor-23 and urinary fractional excretion of calcium (FEca) and phosphorus (FEphos). We examined the associations of ET with each biomarker. In addition, we tested whether the adjustment for biomarkers attenuated the association of ET with lumbar BMD measured by abdominal computed tomography in a subset of 810 women.



In adjusted models, women who used ET were younger in age [62 (SD 8) vs 66 (9) y, P < .001], had lower mean serum calcium [-13 mg/dL (95% confidence interval [CI] -0.17, -0.10), P < .001] and lower FEca [-0.15% (95% CI -0.21, -0.09), P < .001]. Mean serum phosphorus was lower [-0.19 mg/dL (95% CI -0.23, -0.15), P < .001] and FEphos [0.56% (95% CI 0.16, 0.96), P = .007] was higher in women on ET. Mean 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were higher [1.52 ng/dL (95% CI 0.57, 2.47), P = .002, and 0.26 ng/mL (95% CI 0.03, 0.48), P = .03, respectively] in women who used ET. Mean PTH and fibroblast growth factor-23 did not differ significantly by the use of ET. ET use was strongly associated with higher lumbar BMD [12.75 mg/cm³ (95% CI 7.77-17.73), P < .001]; however, mineral metabolism measures did not meaningfully alter this association.



In a multiethnic cohort of postmenopausal women, ET use was associated with lower serum calcium, lower FEca, lower serum phosphorus, and higher FEphos, suggesting these associations are attributable to increased calcium intake into bone and increased urinary phosphorus excretion. ET use was also associated with greater concentrations of vitamin D metabolites. ET-associated differences in these mineral metabolism measures did not meaningfully attenuate the strong association between ET use and lumbar BMD.
Evaluation of a quality improvement collaborative in asthma care: does it improve processes and outcomes of care?

We wanted to examine whether a collaborative to improve asthma care influences process and outcomes of care in asthmatic adults.



We undertook a preintervention-postintervention evaluation of 185 patients in 6 intervention clinics and 3 matched control sites that participated in the Institute for Healthcare Improvement Breakthrough Series (BTS) Collaborative for asthma care. The intervention consisted of 3, 2-day educational sessions for teams dispatched by participating sites, which were followed by 3 action periods during the course of a year.



Overall process of asthma care improved significantly in the intervention compared with the control group (change of 10% vs 1%, P = .003). Patients in the intervention group were more likely to attend educational sessions (20% vs 5%, P = .03). Having a written action plan, setting goals, monitoring peak flow rates, and using long-term asthma medications increased between 2% and 19% (not significant), but asthma-related knowledge was unchanged for the 2 groups. Patients in the BTS Collaborative were significantly more likely to be satisfied with clinician and lay educator communication (62% vs 39%, P = .02). Health-related quality of life, asthma-specific quality of life, number of bed days caused by asthma-related illness, and acute care service use were not significantly different between the 2 groups.



The intervention was associated with improved process-of-care measures that have been linked with better outcomes. Patients benefited through increased satisfaction with communication. Follow-up of patients who participated in the intervention may have been too brief to be able to detect significant improvement in health-related outcomes.
Decreased diastolic wall strain is associated with adverse left ventricular remodeling even in patients with normal left ventricular diastolic function

The pathophysiology of diastolic dysfunction is complex, but can be simply described as impaired LV myocardial relaxation and/or increased LV stiffness. The objective of this study is to clarify true normal left ventricular (LV) diastolic function and early stage of diastolic dysfunction before relaxation abnormality develops in patients with normal LV diastolic function using simple diastolic wall strain (DWS) in South Korea.



DWS which is a non-invasive, load-independent, and reproducible estimator of LV stiffness using two-dimensional echocardiography using the difference between posterior wall thickness in systole and diastole to approximate LV stiffness. A total of 349 consecutive patients with normal LV diastolic function by echocardiography were enrolled. According to DWS, patients were divided into two groups: high DWS (≥median 175) vs. low DWS (<median 174).



Patients with low DWS were more obese and showed higher blood pressure, and had more prevalent hypertension and hyperlipidemia. In addition, those with low DWS had higher LV end-systolic volume, LV mass index, E/E' and lower ejection fraction and E' velocity. Among them, higher LVESV and LVMI were independently associated with low DWS.



These data suggests that simple DWS might be helpful in identifying a subgroup of subtle diastolic dysfunction. Our data suggest that early change of diastolic dysfunction might start with abnormal LV geographic changes preceding functional changes.
Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, 51Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 ± 10, Post 70 ± 18 mmol/kg/wt; PL Pre 52 ± 13, Post 46 ± 13 mmol/kg/wt; p = 0.03; estimated difference between means 23.6; 95% confidence interval 1.42–45.8). No significant differences were observed for 51Cr-EDTA clearance (CR Pre 90.4 ± 16.9, Post 96.1 ± 15.0 mL/min/1.73 m2; PL Pre 97.9 ± 21.6, Post 96.4 ± 26.8 mL/min/1.73 m2; p = 0.58; estimated difference between means −0.3; 95% confidence interval −24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population.
What are the four phases of clinical research trials?

Children with neurological and developmental disorders often experience chronic sleep disturbances. Melatonin has been commonly prescribed because of its hypnotic properties. However, trials have had conflicting results. Therefore, researchers assessed the effectiveness of melatonin in treating severe sleep problems in children with neurodevelopmental disorders. A randomised double blind placebo controlled multicentre trial study design was used. The intervention was immediate release melatonin capsules given 45 minutes before the child’s bedtime for a period of 12 weeks. Treatment started with a 0.5 mg capsule, and escalated through 2 mg, 6 mg, and 12 mg, depending on the child’s response to treatment. Participants were 146 children who had a severe sleep problem and had not responded to standardised sleep behaviour advice provided to parents four to six weeks before randomisation. Children were recruited from 19 hospitals across England and Wales. The children were randomised to melatonin (n=70) or placebo (n=76). The outcome measures included subjective (as assessed from sleep diaries completed by the parents) and objective (as recorded by actigraphy) measures of sleep. The researchers reported that children gained little additional sleep on melatonin compared with placebo. However, the children receiving melatonin fell asleep significantly more quickly and they awoke earlier. Which one of the following best describes the phase of the above clinical trial? a) Phase I
Prospective, randomized comparison of gadopentetate and gadobutrol to assess chronic myocardial infarction applying cardiovascular magnetic resonance

We hypothesized that the contrast medium gadobutrol is not inferior compared to Gd-DTPA in identifying and quantifying ischemic late gadolinium enhancement (LGE), even by using a lower dose.



We prospectively enrolled 30 patients with chronic myocardial infarction as visualized by LGE during clinical routine scan at 1.5 T with 0.20 mmol/kg Gd-DTPA. Participants were randomized to either 0.15 mmol/kg gadobutrol (group A) or 0.10 mmol/kg gadobutrol (group B). CMR protocol was identical in both exams. LGE was quantified using a semiautomatic approach. Signal intensities of scar, remote myocardium, blood and air were measured. Signal to noise (SNR) and contrast to noise ratios (CNR) were calculated.



Signal intensities were not different between Gd-DTPA and gadobutrol in group A, whereas significant differences were detected in group B. SNR of injured myocardium (53.5+/-21.4 vs. 30.1+/-10.4, p = 0.0001) and CNR between injured and remote myocardium (50.3+/-20.3 vs. 27.3+/-9.3, p < 0.0001) were lower in gadobutrol. Infarct size was lower in both gadobutrol groups compared to Gd-DTPA (group A: 16.8+/-10.2 g vs. 12.8+/-6.8 g, p = 0.03; group B: 18.6+/-12.0 g vs. 14.0+/-9.9 g, p = 0.0016).



Taking application of 0.2 mmol/kg Gd-DTPA as the reference, the delineation of infarct scar was similar with 0.15 mmol/kg gadobutrol, whereas the use 0.10 mmol/kg gadobutrol led to reduced tissue contrast.
Immediate effects of a high-velocity spine manipulation in paraspinal muscles activity of nonspecific chronic low-back pain subjects.

High-velocity spinal manipulation is commonly adopted for treating chronic low-back pain (CLBP) and has been associated with changes in muscle activity, but the evidence is controversial. The aim of this study was to analyse the immediate effects of high-velocity spine manipulation on paraspinal activity during flexion-extension trunk movements. Forty nonspecific CLBP patients were randomised into two groups, manipulation (n = 20) and control (n = 20). While the manipulation group received high-velocity spine manipulation at the L4-L5 level, the control group remained lying in the same position. EMG-related variables, perceived pain intensity (100 mm VAS) and finger-floor distance were collected before and after spinal manipulation at the L4-L5 level. EMG surface signals from the right and left paraspinal muscles (L5-S1 level) were acquired during trunk flexion-extension cycles. EMG activity during the static relaxation phase was significantly reduced following intervention for the manipulation group but not for the control group. The extension-phase EMG activity was also reduced after manipulation, but the flexion-phase EMG levels remained unchanged. Accordingly, the percent changes in FRR and ERR were significantly larger for the manipulation group compared to the control. The results suggest that a high-velocity spinal manipulation is able to acutely reduce abnormal EMG activity during the full-flexion static phase and activation during the extension phase.