nils-herrmann/clean_scirepeval huggingface dataset:
Effects of various factors including the CYP2D6 genotype and coadministration of flunitrazepam on the steady-state plasma concentrations of bromperidol and its reduced metabolite

The effects of various factors, including the cytochrome P450 (CYP) 2D6 genotype and the coadministration of flunitrazepam, on the steady-state plasma concentrations (Css) of bromperidol and its reduced metabolite were studied in 62 schizophrenic inpatients receiving bromperidol 12 mg/day. By use of allele-specific PCR analysis, the wild type allele (CYP2D6 * 1A) and four mutated alleles causing either absent (CYP2D6 * 3, CYP2D6 * 4 and CYP2D6 * 5) or decreased (CYP2D6 * 10) CYP2D6 activity were identified. The means (ranges) of the Css of bromperidol and reduced bromperidol corrected to the median body weight were 7.2 (1.3–17.4) and 2.2 (0.4–8.9) ng/ml, respectively. Neither the Css of bromperidol nor that of reduced bromperidol significantly differed among the patients with no (n = 28), one (n = 30) and two mutated alleles (n = 4). The patients coadministered with flunitrazepam (n = 52) had significantly (P < 0.05) higher Css of bromperidol, but not reduced bromperidol, than those not (n = 10). Age, sex and smoking had no significant effects on the Css of these compounds. The present study thus suggests that the polymorphic CYP2D6 is not involved in the metabolism of bromperidol and reduced bromperidol to a major extent. The coadministration of flunitrazepam inhibits the metabolism of bromperidol, but age, sex and smoking do not affect it.
Safinamide as Add-On Therapy to Levodopa in Mid- to Late-Stage Parkinson’s Disease Fluctuating Patients: Post hoc Analysesof Studies 016 and SETTLE

Studies 016 and SETTLE showed that safinamide was safe and effective as adjunct therapy in patients with advanced Parkinson's disease (PD) and motor fluctuations. The addition of safinamide to a stable dose of levodopa alone or with other antiparkinsonian medications significantly increased ON time with no/non-troublesome dyskinesia, decreased OFF time and improved Parkinson's symptoms.



To evaluate the clinical effects of safinamide 100 mg/day on motor fluctuations and cardinal Parkinson's symptoms in specific patient subgroups using pooled data from Studies 016 and SETTLE.



Both studies were double blind, placebo-controlled, randomized, phase 3 trials which enrolled patients with mid- to late-stage PD experiencing motor fluctuations while receiving optimized and stable doses of levodopa, alone or with other dopaminergic treatments. The present post-hoc analyses assessed the change from baseline in ON time (with no or non-troublesome dyskinesia) and OFF time in subgroups of patients who were receiving only levodopa at baseline, who were classified as "mild fluctuators" (daily OFF time ≤4 h), and who were receiving concomitant dopaminergic therapy, with or without amantadine, and the effects of safinamide versus placebo on individual cardinal PD symptoms during ON time.



Safinamide significantly increased mean ON time (with no or non-troublesome dyskinesia) and reduced mean OFF time when used as first adjunct therapy in levodopa-treated patients and patients with mild motor fluctuations. Mean daily ON time (with no or non-troublesome dyskinesia) and OFF time were favorably changed, compared with placebo, to similar extents regardless of whether patients were receiving concomitant dopamine agonists, catechol-O-methyltransferase inhibitors and amantadine. Additionally, safinamide improved bradykinesia, rigidity, tremor and gait.



Safinamide was a safe and effective first adjunct therapy in levodopa-treated patients and improved 4/5 cardinal symptoms of PD while providing benefits to mild and non-mild fluctuators and patients receiving other concomitant dopaminergic therapies.
An in-home geriatric programme for vulnerable community-dwelling older people improves the detection of dementia in primary care.

Dementia is under-diagnosed in primary care. This study investigated whether an in-home geriatric assessment and management programme could improve the identification of patients with dementia in primary care.



A secondary analysis was performed, using data of a randomised controlled trial that studied the effects of an in-home geriatric evaluation and management programme compared with usual care. In this trial, 151 vulnerable community-dwelling patients, aged 70 years and older, participated: 86 in the intervention group and 66 in de control group. The effect of the programme on the dementia detection rate was determined by comparing the number of new dementia diagnoses in both study arms at 6 months follow-up.



Of all 151 participants, 38 (25%) had a registered dementia diagnosis at baseline. During follow-up, 23 of 113 patients without a registered dementia diagnosis at baseline were identified as suffering from dementia. The difference between the numbers of new dementia diagnoses in the intervention group (19 of 66 patients) and the control group (4 of 47 patients) was significant. (p = 0.02)



An in-home geriatric assessment and management programme for vulnerable older patients improves the detection of dementia and can therefore contribute to overcoming of under-diagnosis of dementia.
A comprehensive evaluation of the proficiency testing program for the HIV-1 BED incidence assay.

The HIV-1 BED incidence assay was developed at the Centers for Disease Control and Prevention and since 2005 has been available as a commercial kit for use in HIV-1 incidence surveillance. A BED-specific proficiency testing (PT) program was initiated in 2006 that included a panel of eight coded specimens (six unique and two duplicates) to participating laboratories. The number of participating laboratories increased from 12 to 38 from 2006 to 2009. Overall, 96.1% of the laboratories reported results, and 95.4% of those reporting achieved a 100% score. The observed mean normalized optical density (OD-n) values of all participants correlated well with the expected OD-n values for all specimens (R(2) = 0.98) used for seven PT rounds. BED testing demonstrated high reproducibility among all laboratories, with an agreement of 99.3% (574/578) between initial and confirmatory classification and regression statistics of R(2) = 0.96, slope = 1.022, and intercept = 0.0066. Reproducibility among duplicate specimens was very high during each PT round, with mean deviation of 1.8%. Analysis of controls and calibrator specimen for all 343 runs showed a coefficient of variation of ca. 20% for raw ODs in the dynamic range, which was reduced to <10% when the OD was normalized (OD-n). Most laboratories that failed the PT assessment had transcriptional errors, kit reagent problems, or specimen handling errors. Thus, the BED-specific PT program enabled us to track performance of different laboratories conducting the BED assay while identifying areas for improvements. This program will also serve as a template for future PT programs for new incidence assays as they become available.
A Participatory Workplace Intervention for Employees With Distress and Lost Time: A Feasibility Evaluation Within a Randomized Controlled Trial

Little is known about feasibility and acceptability of return to work (RTW) interventions for mental health problems. RTW for mental health problems is more complicated than for musculoskeletal problems due to stigmatization at the workplace. A participatory workplace intervention was developed in which an employee and supervisor identify and prioritize obstacles and solutions for RTW guided by a RTW coordinator. This paper is a feasibility study of this innovative intervention for employees with distress. The aims of this study were to describe the reach and extent of implementation of the workplace intervention, the satisfaction and expectations of all stakeholders, and the intention to use the workplace intervention in the future.  Eligible for this study were employees who had been on sick leave from regular work for 2–8 weeks with distress. Data were collected from the employees, their supervisors, RTW coordinators, and occupational physicians by means of standardized matrices and questionnaires at baseline and 3 months follow-up. Reach, implementation, satisfaction, expectations, and maintenance regarding the workplace intervention were described.  Of the 56 employees with distress eligible to receive the workplace intervention, 40 employees, their supervisors and RTW coordinators actually participated in the intervention. They identified 151 obstacles for RTW mostly related to job design, communication, mental workload and person-related stress factors. The 281 consensus-based solutions identified were mostly related to job design, communication and training. Of those solutions, 72% was realized at the evaluation with the employee and supervisor. Overall, employees, supervisors and occupational health professionals were satisfied with the workplace intervention and occupational health professionals rated it with a 7.1. Time-investment was the only barrier for implementation reported by the occupational health professionals.  The results of this study indicate a high feasibility for a broad implementation of a participatory workplace intervention for employees with distress and lost time, and their supervisors.
The Effect of Cotrimoxazole Prophylactic Treatment on Malaria, Birth Outcomes, and Postpartum CD4 Count in HIV-Infected Women

Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp).



Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count.



Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (-77.6 cells/ μ L, 95% CI: -125.2, -30.1) and not receiving antiretrovirals (-33.7 cells/ μ L, 95% CI: -58.6, -8.8).



Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination.
Effect of patient navigation on enrollment in cardiac rehabilitation.

lute rates of adverse behaviors were low, such as HIV risk behaviors, most Americans adhere to public health recommendations, and the lack of difference between HCWs and other Americans is reassuring. Perhaps most surprisingly, female HCWs older than 50 years were less likely to adhere to the guidelines of having a mammogram within the past 2 years. Other studies have also observed this paradoxical, unexplained finding. Among respondents who were not college graduates, HCWs were more likely to have a personal physician than non-HCWs, an association absent among graduates. If confirmed, working in health care may improve access preferentially among individuals at greatest risk for not having a regular provider. Specific limitations should be mentioned. The BRFSS is limited to self-reported information, which cannot be externally confirmed. Because HCWs did not report their specific positions, we cannot differentiate between physicians, nurses, aides, and other HCWs. In conclusion, HCWs adhered variably to healthy life choices, often no differently and, for mammography, even less than other Americans. Interventions directed toward HCWs or their employers may improve overall adherence rates. Despite serving as role models, HCWs frequently do not “practice what they preach.”
Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial

The MRC Multicentre trial for Early Epilepsy and Single Seizures (MESS) showed a reduced risk of further seizures in patients, for whom treatment with antiepileptic drugs was uncertain, who were randomly assigned immediate treatment compared with delayed treatment. However, there was no evidence of an effect on [corrected] long-term remission rates. This study was undertaken to assess the role of patient characteristics and treatment in the prediction of seizure recurrence. This will enable decision-making on the basis of the perceived risk of treatment compared with the benefit of reducing the risk of further seizures in the initial years after diagnosis.



A prognostic model was developed based on individual patient data from MESS to enable identification of patients at low, medium, or high risk of seizure recurrence. A split-sample approach was used in which the model was developed on a subsample of the full data and validated on the remainder of the sample. Distinction of the prognostic groups and predictive accuracy of the model were assessed.



Number of seizures of all types at presentation, presence of a neurological disorder, and an abnormal electroencephalogram (EEG) were significant factors in indicating future seizures. Individuals with two or three seizures, a neurological disorder, or an abnormal EEG were identified as the medium-risk group, those with two of these features or more than three seizures as the high-risk group, and those with a single seizure only as the low-risk group.



The model shows that there is little benefit to immediate treatment in patients at low risk of seizure recurrence, but potentially worthwhile benefits are seen in those at medium and high risk.
Opportunistic detection of atrial fibrillation in subjects aged 65 years or older in primare care: a randomised clinical trial of efficacy. DOFA-AP study protocol

Clinical Practice Guidelines recommend using peripheral blood pulse measuring as a screening test for Atrial Fibrillation. However, there is no adequate evidence supporting the efficacy of such procedure in primary care clinical practice. This paper describes a study protocol designed to verify whether early opportunistic screening for Atrial Fibrillation by measuring blood pulse is more effective than regular practice in subjects aged 65 years attending primary care centers.



An cluster-randomized controlled trial conducted in Primary Care Centers of the Spanish National Health Service. A total of 269 physicians and nurses will be allocated to one of the two arms of the trial by stratified randomization with a 3:2 ratio (three practitioners will be assigned to the Control Group for every two practitioners assigned to the Experimental Group). As many as 12 870 patients aged 65 years or older and meeting eligibility criteria will be recruited (8 580 will be allocated to the Experimental Group and 4 290 to the Control Group). Randomization and allocation to trial groups will be carried out by a central computer system. The Experimental Group practitioners will conduct an opportunistic case finding for patients with Atrial Fibrillation, while the Control Group practitioners will follow the regular guidelines. The first step will be finding new Atrial Fibrillation cases. A descriptive inferential analysis will be performed (bivariate and multivariate by multilevel logistic regression analysis).



If our hypothesis is confirmed, we expect Primary Care professionals to take a more proactive approach and adopt a new protocol when a patient meeting the established screening criteria is identified. Finally, we expect this measure to be incorporated into Clinical Practice Guidelines.
Higher Hemoglobin A1c After Discharge Is an Independent Predictor of Adverse Outcomes in Patients With Acute Coronary Syndrome　- Findings From the PACIFIC Registry.

Optimal medical therapy (OMT) and the management of coronary risk factors are necessary for secondary prevention of major adverse cardiac and cerebrovascular events (MACCE) in post-acute coronary syndrome (ACS) patients. However, the effect of post-discharge patient adherence has not been investigated in Japanese patients.



The Prevention of AtherothrombotiC Incidents Following Ischemic Coronary Attack (PACIFIC) registry was a multicenter, prospective observational study of 3,597 patients with ACS. Death or MACCE occurred in 229 patients between hospitalization and up to 1 year after discharge. Among 2,587 patients, the association between OMT adherence and risk factor control at 1 year and MACCE occurring between 1 and 2 years after discharge was assessed. OMT was defined as the use of antiplatelet agents, angiotensin-converting enzyme inhibitors, β-blockers, and statins. Risk factor targets were: low-density lipoprotein-cholesterol <100 mg/dl, HbA1c <7.0%, non-smoking status, blood pressure <130/80 mmHg, and 18.5≤body mass index≤24.9 kg/m(2). The incidence of MACCE was 1.8% and associated with female sex (P=0.020), age ≥75 years (P=0.004), HbA1c ≥7.0% (P=0.004), LV ejection fraction <35% (P<0.001), estimated glomerular filtration rate <60 ml/min (P=0.008), and history of cerebral infarction (P=0.003). In multivariate analysis, lower post-discharge HbA1c was strongly associated with a lower risk of MACCE after ACS (P=0.004).



Hyperglycemia after discharge is a crucial target for the prevention of MACCE in post-ACS patients.
Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus

We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE.



Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS(s)).



Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10(-16)) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10(-7)), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results.



Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women.
Mitochondrial abnormality associates with type-specific neuronal loss and cell morphology changes in the pedunculopontine nucleus in Parkinson disease.

Cholinergic neuronal loss in the pedunculopontine nucleus (PPN) associates with abnormal functions, including certain motor and nonmotor symptoms. This realization has led to low-frequency stimulation of the PPN for treating patients with Parkinson disease (PD) who are refractory to other treatment modalities. However, the molecular mechanisms underlying PPN neuronal loss and the therapeutic substrate for the clinical benefits following PPN stimulation remain poorly characterized, hampering progress toward designing more efficient therapies aimed at restoring the PPN's normal functions during progressive parkinsonism. Here, we investigated postmortem pathological changes in the PPN of PD cases. Our study detected a loss of neurons producing gamma-aminobutyric acid (GABA) as their output and glycinergic neurons, along with the pronounced loss of cholinergic neurons. These losses were accompanied by altered somatic cell size that affected the remaining neurons of all neuronal subtypes studied here. Because studies showed that mitochondrial dysfunction exists in sporadic PD and in PD animal models, we investigated whether altered mitochondrial composition exists in the PPN. A significant up-regulation of several mitochondrial proteins was seen in GABAergic and glycinergic neurons; however, cholinergic neurons indicated down-regulation of the same proteins. Our findings suggest an imbalance in the activity of key neuronal subgroups of the PPN in PD, potentially because of abnormal inhibitory activity and altered cholinergic outflow.
A randomized and open-label trial evaluating the addition of pazopanib to lapatinib as first-line therapy in patients with HER2-positive advanced breast cancer

This phase II study (VEG20007; NCT00347919) with randomized and open-label components evaluated first-line lapatinib plus pazopanib therapy and/or lapatinib monotherapy in patients with human epidermal growth factor receptor type 2 (HER2)-positive advanced/metastatic breast cancer. Patients were enrolled sequentially into two cohorts: Cohort 1, patients were randomly assigned to lapatinib 1,000 mg plus pazopanib 400 mg or lapatinib 1,500 mg monotherapy; Cohort 2, patients received lapatinib 1,500 mg plus pazopanib 800 mg. The primary endpoint was week-12 progressive disease rate (PDR) for Cohort 1. The principal secondary endpoint was week-12 response rate (RR) for Cohort 2. Efficacy was assessed in patients with centrally confirmed HER2 positivity (modified intent-to-treat population [MITT]). The study enrolled 190 patients (Cohort 1, combination n = 77, lapatinib n = 73; Cohort 2, n = 40). The MITT population comprised n = 141 (Cohort 1) and n = 36 (Cohort 2). In Cohort 1, week-12 PDRs were 36.2 % (combination) versus 38.9 % (lapatinib; P = 0.37 for the difference). Week-12 RRs were 36.2 % (combination) versus 22.2 % (lapatinib). In Cohort 2, week-12 RR was 33.3 %. In Cohort 1, grade 3/4 adverse events (AEs) included diarrhea (combination, 9 %; lapatinib, 5 %) and hypertension (combination, 5 %; lapatinib, 0 %). Grades 3/4 AEs in Cohort 2 included diarrhea (40 %), hypertension (5 %), and fatigue (5 %). Alanine aminotransferase elevations >5 times the upper limit of normal occurred in Cohort 1 (combination, 18 %; lapatinib, 5 %) and Cohort 2 (20 %). Upon conclusion, the combination of lapatinib plus pazopanib did not improve PDR compared with lapatinib monotherapy, although RR was increased. Toxicity was higher with the combination, including increased diarrhea and liver enzyme elevations.
Two dopamine genes related to reports of childhood retrospective inattention and conduct disorder symptoms

The 7-repeat allele of the dopamine receptor D4 gene (DRD4) and the 10 repeat allele of the dopamine transporter gene (DAT1) have shown association and linkage with symptoms of attention deficit hyperactivity disorder (ADHD) in childhood. The parents of ADHD children (clinic group, n = 80 fathers and 107 mothers) and control children (control group, n = 42 fathers and 51 mothers) were the focus of this study. These parents reported retrospectively on their level of ADHD Inattention and Conduct Disorder symptoms in adolescence. In analyses of the relation of symptom levels to the DRD4 and DAT1 genotypes, fathers possessing the 7 repeat DRD4 allele had greater levels of both inattention and conduct disorder symptoms. Mothers with the 10/10 genotype had higher levels of inattention symptoms. Thus, genetic associations found in children may be replicable in their parents.