nils-herrmann/clean_scirepeval huggingface dataset:
Single versus combination antibiotic therapy in adults hospitalised with community-acquired pneumonia.

We read with interest the recent paper by Rodrigo et al, who reported that adding a macrolide to the antibiotic regimen in patients with community-acquired pneumonia (CAP) resulted in lower mortality. Their data are very promising. However, we have a concern about the recommendations to implement macrolides as standard treatment for CAP. We agree with Brown and Hill, who stated in their editorial that adding a macrolide might result in an increased risk of complications and might encourage antibiotic resistance. Furthermore, they mention that it is difficult to explain how the addition of a macrolide improves survival. Rodrigo, Brown and Hill suggest that randomised controlled trials should be performed comparing b-lactam/macrolide combination therapy with single-agent therapy. In 2005 we published the results of just such a study in Thorax. In our study, there was no difference in outcome between the two treatment strategies among non-ICU admitted patients. However, in ICU-admitted patients the death rate was significantly higher in the group of patients receiving b-lactam/ macrolide combination therapy. A possible explanation for this remarkable finding is that in some of these patients death was inevitable despite appropriate treatment. Furthermore, this study was not powered to evaluate the outcome among ICU patients. In all patients we had performed extensive microbiological investigations, including bronchoscopy in cases of mechanical ventilation. In 82% of the ICU patients we identified a pathogen. In view of these results, we would like to state that adding a macrolide to an antibiotic regimen does not always result in a better outcome in non-ICU and ICU patients and furthermore, potentially increases the rate of microbial resistance owing to antibiotic overuse. We think that more attention should be paid to performing extensive microbiological investigations in hospitalised patients and to adaptation of antibiotic treatment when possible. M M van der Eerden, W G Boersma Department of Pulmonary diseases, Erasmus Medical Centre, Rotterdam, The Netherlands Department of Lung diseases, Medical Centre Alkmaar, Alkmaar, The Netherlands
Effectiveness of e-learning in continuing medical education for occupational physicians

Within a clinical context e-learning is comparable to traditional approaches of continuing medical education (CME). However, the occupational health context differs and until now the effect of postgraduate e-learning among occupational physicians (OPs) has not been evaluated.



To evaluate the effect of e-learning on knowledge on mental health issues as compared to lecture-based learning in a CME programme for OPs.



Within the context of a postgraduate meeting for 74 OPs, a randomized controlled trial was conducted. Test assessments of knowledge were made before and immediately after an educational session with either e-learning or lecture-based learning.



In both groups, a significant gain in knowledge on mental health care was found (P < 0.05). However, there was no significant difference between the two educational approaches.



The effect of e-learning on OPs' mental health care knowledge is comparable to a lecture-based approach. Therefore, e-learning can be beneficial for the CME of OPs.
Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study.

Exhaled nitric oxide (eNO) is decreased in cystic fibrosis (CF). The effect of oral L-arginine, the precursor of enzymatic nitric oxide (NO) formation, on airway NO in patients with CF was studied. In a pilot study, oral L-arginine was given in a single dose of 200 mg x kg(-1) body weight to eight healthy controls and eight CF patients. Subsequently, the same L-arginine dose was given to 10 patients with CF (five females) t.i.d. for 6 weeks in a randomised double-blind placebo-controlled crossover study. A single dose of oral L-arginine resulted in a 5.5-fold increase of L-arginine in plasma and a 1.3-fold increase of L-arginine in sputum after 2 h. Maximum eNO, within 3 h of L-arginine intake, increased significantly in both CF patients (5.4+/-2.1 ppb versus 8.3+/-3.5 ppb) and controls (18.0+/-8.1 ppb versus 26.4+/-12.3 ppb). Supplementation of L-arginine for 6 weeks resulted in a sustained increase in eNO compared to placebo (9.7+/-5.7 ppb versus 6.3+/-3.1 ppb). An effect of L-arginine supplementation on forced expiratory volume in one second was not observed. These data indicate that airway nitric oxide formation in cystic fibrosis patients can be augmented with oral L-arginine supplementation.
Effectiveness of alcohol treatment interventions integrated into routine tuberculosis care in Tomsk, Russia.

To test the feasibility and effectiveness of brief counseling intervention (BCI) and naltrexone integrated into tuberculosis (TB) care in Tomsk, Russia.



Using a factorial randomized controlled trial design, patients were randomized into: naltrexone (NTX), brief behavioral compliance enhancement therapy (BBCET), treatment as usual (TAU) and BCI.



In the Tomsk Oblast, hospitalized TB patients diagnosed with alcohol use disorders (AUDs) by the DSM-IV were referred at the start of TB treatment. Of the 196 participants, the mean age was 41 years and 82% were male. Severe TB (84.7% had cavitary disease) and smoking (92.9%) were common. The majority had a diagnosis of an AUD (63.0%); 27.6% reported nearly daily drinking and consumed a median of 16 standard drinks per day.



Primary outcomes were 'favorable' TB outcome (cured, completed treatment) and change in mean number of abstinent days in the last month of study compared with baseline. Change in mean number of heavy drinking days, defined as four drinks per day and five drinks per day for women and men, respectively, and TB adherence, measured as percentage of doses taken as prescribed under direct observation, were secondary outcomes. Analysis based on 'intention-to-treat' was performed for multivariable analysis.



Primary TB and alcohol end-points between naltrexone and no-naltrexone or BCI and no-BCI groups did not differ significantly. TB treatment adherence and change in number of heavy drinking days also did not differ significantly among treatment arms. Among individuals with a prior quitting attempt (n = 111), naltrexone use was associated with an increased likelihood of favorable TB outcomes (92.3% versus 75.9%, P = 0.02).



In Tomsk Oblast, Russia, tuberculosis patients with severe alcohol use disorders who were not seeking alcohol treatment did not respond to naltrexone or behavioral counselling integrated into tuberculosis care; however, those patients with past attempts to quit drinking had improved tuberculosis outcomes.
Impact of group nutrition education and surplus value of Prochaska-based stage-matched information on health-related cognitions and on Mediterranean nutrition behavior.

This study compares the effect of two interventions focussed on the promotion of Mediterranean nutrition behavior. The target groups are persons with three risk factors for development of cardiovascular disease. The study region is a socio-economically deprived area in the Netherlands. The first intervention consisted of three meetings in which the positive health effects of a Mediterranean diet were discussed in group sessions. In the additional intervention stage-matched information based on the Transtheoretical Model of behavior change was given. Both intervention groups were compared with a control group, which received only a printed leaflet with the Dutch nutritional guidelines. At baseline the three subgroups were comparable and after 16 weeks both intervention strategies resulted in significant changes in comparison with the control condition. For fish consumption, both strategies resulted in more positive attitudes, social norms, stronger intentions, more progress in stage of change and better nutritional intake. For fruit/vegetables consumption, the effects of both strategies were limited to stage of change and nutritional intake. Additional individually stage-matched tailored letters did not result in more progress on any of the dependent variables. We conclude that substantial nutritional behavior change can be achieved by interactive group education in socio-economically deprived population groups.
Effects of Azithromycin in bronchiolitis obliterans syndrome after hematopoietic SCT—a randomized double-blinded placebo-controlled study

Bronchiolitis obliterans syndrome (BOS) is an important complication after hematopoietic SCT (HSCT). Recent observations suggested that azithromycin might improve lung function in BOS after HSCT. We conducted a randomized double-blinded placebo-controlled study on azithromycin in patients with BOS after HSCT. The treatment group (n=10) received oral azithromycin 250 mg daily while the control group (n=12) received placebo daily for 12 weeks. Respiratory symptoms were assessed by the St George Respiratory Questionnaires and spirometry at baseline (drug commencement), 1, 2, 3 (drug cessation) and 4 months (1 month after drug cessation). There was no significant difference in the baseline demographic characteristics between the treatment and the control groups in age, gender, time from HSCT to BOS, time since diagnosis of BOS, chronic GVHD, baseline respiratory symptom scores and baseline forced expiratory volume in 1 s (FEV1). Throughout and after 3 months of treatment, there were no significant changes in respiratory symptom scores and FEV1 measurements between the treatment and the control groups. In conclusion, there was no significant benefit of 3 months of oral azithromycin on the respiratory symptoms and lung function in patients with relatively late BOS after HSCT in this randomized placebo-controlled study.
Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus

To determine the effects of empagliflozin on adiposity indices among patients with type 2 diabetes mellitus.



Changes in weight, waist circumference, estimated total body fat, index of central obesity and visceral adiposity index were assessed using analysis of covariance and testing of treatment by strata for age, sex and baseline waist circumference in patients with type 2 diabetes mellitus randomized to blinded treatment with empagliflozin versus placebo in clinical trials of 12 weeks (cohort 1) or 24 weeks (cohort 2) duration.



This study comprised 3300 patients (cohort 1, N = 823; cohort 2, N = 2477). Empagliflozin reduced weight, waist circumference and adiposity indices versus placebo in both cohorts. Adjusted mean (95% confidence interval) change from baseline in empagliflozin versus placebo was -1.7 kg (-2.1 to -1.4 kg) and -1.9 kg (-2.1 to -1.7 kg) for body weight (p < 0.001); -1.3 cm (-1.8 to -0.7 cm) and -1.3 cm (-1.7 to -1.0 cm) for waist circumference (p < 0.001); -0.2% (-0.7% to 0.3%; p = 0.45) and -0.3% (-0.7% to 0.0%; p = 0.08) for estimated total body fat; -0.007 (-0.011 to -0.004) and -0.008 (-0.010 to -0.006) for index of central obesity (p < 0.001); and -0.3 (-0.5 to 0.0; p = 0.07) and -0.4 (-0.7 to -0.1; p = 0.003) for visceral adiposity index in cohorts 1 and 2, respectively. Adipose reductions were seen across most age, sex and waist circumference subgroups.



Empagliflozin significantly reduced weight and adiposity indices with the potential to improve cardiometabolic risk among patients with type 2 diabetes mellitus.
Values and beliefs of psychedelic drug users: a cross-cultural study.

Psychedelic drugs such as LSD and psilocybin are often claimed to be capable of inducing life-changing experiences described as mystical or transcendental, especially if high doses are taken. The present study examined possible enduring effects of such experiences by comparing users of psychedelic drugs (n = 88), users of nonpsychedelic illegal drugs (e.g., marijuana, amphetamines) (n = 29) and non illicit drug-using social drinkers (n = 66) on questionnaire measures of values, beliefs and emotional empathy. Samples were obtained from Israel (n = 110) and Australia (n = 73) in a cross-cultural comparison to see if values associated with psychedelic drug use transcended culture of origin. Psychedelic users scored significantly higher on mystical beliefs (e.g., oneness with God and the universe) and life values of spirituality and concern for others than the other groups, and lower on the value of financial prosperity, irrespective of culture of origin. Users of nonpsychedelic illegal drugs scored significantly lower on a measure of coping ability than both psychedelic users and non illicit drug users. Both groups of illegal drug users scored significantly higher on empathy than non illicit drug users. Results are discussed in the context of earlier findings from Pahnke (1966) and Doblin (1991) of the transformative effect of psychedelic experiences, although the possibility remains that present findings reflect predrug characteristics of those who chose to take psychedelic drugs rather than effects of the drugs themselves.
Family and youth factors associated with health beliefs and health outcomes in youth with type 1 diabetes.

To examine the association of family organization with metabolic control in adolescents with type 1 diabetes through the mechanisms of family self-efficacy for diabetes and disease management.



Data from the baseline assessment of a longitudinal RCT were used, wherein 257 adolescent-parent dyads (adolescents aged 11-14) each completed the family organization subscale of the Family Environment Scale, the self-efficacy for Diabetes Self-Management Scale, the Diabetes Behavior Rating Scale, and 2 24-hr diabetes interviews.



Structural equation modeling showed greater family organization was associated indirectly with better disease management behaviors via greater family self-efficacy (β = .38, p < .001). Greater self-efficacy was indirectly associated with better metabolic control via better disease management both concurrently (β = -.37, p < .001) and prospectively (β = -.26, p < .001). The full model indicates more family organization is indirectly associated with better metabolic control concurrently and prospectively through greater self-efficacy and better disease management (β = -.13, p < .001).



Understanding the mechanisms by which family organization is associated with metabolic control provides insight into possible avenues of prevention/intervention for better diabetes management.
Night blood pressure responses to atenolol and hydrochlorothiazide in black and white patients with essential hypertension.

Night blood pressure (BP) predicts patient outcomes. Variables associated with night BP response to antihypertensive agents have not been fully evaluated in essential hypertension.



We sought to measure night BP responses to hydrochlorothiazide (HCTZ), atenolol (ATEN), and combined therapy using ambulatory blood pressure (ABP) monitoring in 204 black and 281 white essential hypertensive patients. Initial therapy was randomized; HCTZ and ATEN once daily doses were doubled after 3 weeks and continued for 6 more weeks with the alternate medication added for combined therapy arms. ABP was measured at baseline and after completion of each drug. Night, day, and night/day BP ratio responses (treatment - baseline) were compared in race/sex subgroups.



Baseline night systolic BP and diastolic BP, and night/day ratios were greater in blacks than whites (P < 0.01, all comparisons). Night BP responses to ATEN were absent and night/day ratios increased significantly in blacks (P < 0.05). At the end of combined therapy, women, blacks, and those starting with HCTZ as opposed to ATEN had significantly greater night BP responses (P < 0.01). Variables that significantly associated with ATEN response differed from those that associated with HCTZ response and those that associated with night BP response differed from those that associated with day BP response.



In summary, after completion of HCTZ and ATEN therapy, women, blacks, and those who started with HCTZ had greater night BP responses. Reduced night BP response and increased night/day BP ratios occured with ATEN in blacks. Given the prognostic significance of night BP, strategies for optimizing night BP antihypertensive therapy should be considered.
Dopamine agonists and risk: impulse control disorders in Parkinson's disease.

Impulse control disorders are common in Parkinson's disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a 'Sure' choice and a 'Gamble' choice of moderate risk. To commence each trial, in the 'Gain' condition, individuals started at $0 and in the 'Loss' condition individuals started at -$50 below the 'Sure' amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk ('Gamble Risk'). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the 'Gain' relative to the 'Loss' condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.
Sorafenib Plus Ixabepilone as First-Line Treatment of Metastatic HER2-Negative Breast Cancer: A Sarah Cannon Research Institute Phase I/II Trial.

The purposes of the present phase I/II trial were (1) to define tolerable doses of ixabepilone and sorafenib when used in combination and (2) to evaluate the efficacy and toxicity of this combination in the treatment of patients with human epidermal growth factor receptor-negative metastatic breast cancer (MBC).



The eligible patients had human epidermal growth factor receptor-negative MBC and had not received previous chemotherapy in the metastatic setting. All patients received ixabepilone intravenously on day 1 of each 21-day treatment cycle; sorafenib was administered orally twice daily. Patients in phase II received the maximum doses identified in phase I. The patients were reevaluated after the completion of 3 treatment cycles; treatment continued until disease progression or intolerable toxicity. A total of 67 patients were required in phase II to demonstrate increased median progression-free survival from 4.2 to 6.2 months (90% power, α = 0.05).



Ten patients entered the phase I portion; the maximum tolerated doses were ixabepilone 32 mg/m(2) and sorafenib 400 mg orally twice daily. A total of 76 patients were treated at the phase II dose. The median progression-free survival was 4.8 months (95% confidence interval, 3.5-6.3 months). The overall response rate was 37%. The regimen was difficult to tolerate for many patients; 20 patients discontinued because of toxicity, and dose reductions were frequent. The common toxicities included neutropenia, fatigue, rash, and neuropathy.



The combination of ixabepilone and sorafenib was poorly tolerated as first-line treatment of patients with MBC. The activity of the combination was similar to the activity previously reported with single-agent ixabepilone or taxanes. Further development of this combination is not recommended.
Chiropractic spinal manipulative therapy for migraine: a study protocol of a single-blinded placebo-controlled randomised clinical trial

Migraine affects 15% of the population, and has substantial health and socioeconomic costs. Pharmacological management is first-line treatment. However, acute and/or prophylactic medicine might not be tolerated due to side effects or contraindications. Thus, we aim to assess the efficacy of chiropractic spinal manipulative therapy (CSMT) for migraineurs in a single-blinded placebo-controlled randomised clinical trial (RCT).



According to the power calculations, 90 participants are needed in the RCT. Participants will be randomised into one of three groups: CSMT, placebo (sham manipulation) and control (usual non-manual management). The RCT consists of three stages: 1 month run-in, 3 months intervention and follow-up analyses at the end of the intervention and 3, 6 and 12 months. The primary end point is migraine frequency, while migraine duration, migraine intensity, headache index (frequency x duration x intensity) and medicine consumption are secondary end points. Primary analysis will assess a change in migraine frequency from baseline to the end of the intervention and follow-up, where the groups CSMT and placebo and CSMT and control will be compared. Owing to two group comparisons, p values below 0.025 will be considered statistically significant. For all secondary end points and analyses, a p value below 0.05 will be used. The results will be presented with the corresponding p values and 95% CIs.


ETHICS AND DISSEMINATION
The RCT will follow the clinical trial guidelines from the International Headache Society. The Norwegian Regional Committee for Medical Research Ethics and the Norwegian Social Science Data Services have approved the project. Procedure will be conducted according to the declaration of Helsinki. The results will be published at scientific meetings and in peer-reviewed journals.
Poor Sustained Virological Response in a Multicenter Real-Life Cohort of Chronic Hepatitis C Patients Treated with Pegylated Interferon and Ribavirin plus Telaprevir or Boceprevir

There are limited data analyzing the effectiveness of boceprevir (BOC) or telaprevir (TVR) in combination with pegylated interferon (PEG-IFN) plus ribavirin (RBV) in a real-life patient cohort. In clinical trials, patients with chronic hepatitis C (CHC) treated with BOC or TVR plus PEG-IFN and RBV achieved sustained virological response (SVR) rates of 70 %. However, it is not clear whether similar results can be realized in routine practice. Our goal is to examine SVR rates of these triple regimens for CHC in a multicenter real-life patient cohort. We retrospectively studied 200 consecutive CHC genotype 1 patients who were initiated on PEG-IFN, RBV, and either TVR (n = 113) or BOC (n = 87) from July 2011 to February 2014 at two US academic liver clinics, a Veterans Affairs liver clinic and a community gastroenterology clinic. Both BOC and TVR treatment groups were similar in regard to comorbidities, BMI, and HCV RNA levels. BOC patients were more likely to have cirrhosis than TVR patients (47 vs. 24 %, P = 0.001). SVR rates were low in both cohorts (40 % for BOC, 53 % for TVR, P = 0.05). On multivariate logistic regression, treatment adherence by the “80/80/80 rule,” diagnosis of cirrhosis, and use of erythropoietin were statistically significant predictors for SVR. Of these, treatment adherence was the strongest predictor (OR 4.43, 95 % CI 2.8–6.06, P < 0.001). SVR was much lower in a real-life patient cohort than in clinical trials (53 % for TVR and 40 % for BOC, compared to 66–75 % in clinical trials).