nils-herrmann/clean_scirepeval huggingface dataset:
Single-pill combination therapy in the initial treatment of marked hypertension: a propensity-matched analysis.

Many drugs combinations are available and equally recommended for the initial treatment of patients with marked blood pressure (BP) elevation and high cardiovascular risk.



To investigate safety and efficacy of such combination therapies.



Prospectively collected data were retrospectively reviewed, inclusion criteria were: initial single-pill combination therapy, availability of clinical and echocardiographic 6-month follow-up. Six treatment groups were identified: Enalapril 20 mg+ Hydrochlorothiazide 12.5 mg (E/H), E 20 mg + Lercanidipine 10 mg (E/L), Ramipril 2.5 mg+ H 12.5 mg (R/H), Perindopril 5 mg+ Amlodipine 5 mg (P/A), Olmesartan 40 mg+ H 12.5 mg (O/H) and Telmisartan 40 mg+ H 12.5 mg (T/H). To avoid selection bias a Propensity score (goodness of fit: c-statistic 0.78, p = 0.0001) was used to select comparable cohorts of patients (n = 142 each).



After 4 weeks of treatment BP goal was achieved by 624/852 (73.2%) patients, and adverse events were registered in 24/852 (2.8%) patients. After 6 months, 562/624 (90.1%) patients maintained the BP goal. Six-month responder rate was significantly higher in the E/L (69.0%) and P/A (68.3%) groups (p = 0.05); especially among diabetics (52.0% and 51.0%, respectively; p = 0.003). Patients receiving E/L (-19.8 ± 3.2 mmHg) and P/A (-19.9 ± 4.6 mmHg) showed greater reductions of diastolic BP (p = 0.03); whereas reductions of systolic BP were similar between treatment groups (p = 0.46). Echocardiographic follow-up revealed greater left ventricular reverse remodeling among patients receiving ACE-inhibitors (E/L, R/H, E/H and P/A), but this trend did not reach statistical significance.



Single-pill fixed-dose combination therapies are highly effective and safe in the study settings. Best clinical and echocardiographic outcomes were noted among patients receiving E/L, R/H and P/A.
Improvement in subjective and objective neurocognitive functions in patients with major depressive disorder: a 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study.

Although many patients with major depressive disorder (MDD) complain of neurocognitive impairment, the effects of antidepressant medications on neurocognitive functions remain unclear. This study compares neurocognitive effects of tianeptine and escitalopram in MDD. Patients with MDD (N = 164) were randomly assigned in a 1:1 ratio to either tianeptine (37.5 mg/d) or escitalopram (10 mg/d) for 12 weeks. Outcome measures included clinical improvement, subjective cognitive impairment on memory and concentration, the Mini-Mental State Examination, the Continuous Performance Test, the Verbal Learning Test, and the Raven Progressive Matrices, assessed every 4 weeks. After 12 weeks, the tianeptine group showed significant improvement in commission errors (P = 0.002), verbal immediate memory (P < 0.0001), Mini-Mental State Examination (P < 0.0001), delayed memory (P < 0.0001), and reasoning ability (P = 0.0010), whereas the escitalopram group improved in delayed memory and reasoning ability but not in the other measures. Both groups significantly improved in subjective cognitive impairment in memory (P < 0.0001) and concentration (P < 0.0001). Mixed effects model repeated measures analyses revealed that the tianeptine group had a significant improvement in scores of commission errors (F = 6.64, P = 0.011) and verbal immediate memory (F = 4.39, P = 0.038) from baseline to 12 weeks, compared with the escitalopram group, after controlling for age, sex, education years, baseline scores, and changes of depression severity. The treatment of MDD with tianeptine led to more improvements in neurocognitive functions, especially in commission errors and verbal immediate memory, compared with escitalopram, after controlling for changes in depression severity. Both drugs improved subjective cognitive impairment of memory and concentration.
Prevalence and clinical characteristics of diabetic peripheral neuropathy in hospital patients with Type 2 diabetes in Korea.

Diabetic peripheral neuropathy is a common complication of diabetes. This cross-sectional study investigated the prevalence and clinical characteristics of this neuropathy in patients with Type 2 diabetic mellitus treated at hospitals in Korea.



Questionnaires and medical records were used to collect data on 4000 patients with Type 2 diabetes from the diabetes clinics of 40 hospitals throughout Korea. Diabetic peripheral neuropathy was diagnosed based on a review of medical records or using the Michigan Neuropathy Screening Instrument score and monofilament test.



The prevalence of neuropathy was 33.5% (n = 1338). Multivariate analysis revealed that age, female sex, diabetes duration, lower glycated haemoglobin, treatment with oral hypoglycaemic agents or insulin, presence of retinopathy, history of cerebrovascular or peripheral arterial disease, presence of hypertension or dyslipidaemia, and history of foot ulcer were independently associated with diabetic peripheral neuropathy. Of the patients with neuropathy, 69.8% were treated for the condition and only 12.6% were aware of their neuropathy.



There was a high prevalence of peripheral neuropathy in patients with Type 2 diabetes in Korea and those patients were far more likely to have complications or co-morbidities. The proper management of diabetic peripheral neuropathy deserves attention from clinicians to ensure better management of diabetes in Korea.
Socioeconomic status and incidence of sudden cardiac arrest.

Low socioeconomic status is associated with poor cardiovascular health. We evaluated the association between socioeconomic status and the incidence of sudden cardiac arrest, a condition that accounts for a substantial proportion of cardiovascular-related deaths, in seven large North American urban populations.



Using a population-based registry, we collected data on out-of-hospital sudden cardiac arrests occurring at home or at a residential institution from Apr. 1, 2006,  2007. We limited the analysis to cardiac arrests in seven metropolitan areas in the United States (Dallas, Texas; Pittsburgh, Pennsylvania; Portland, Oregon; and Seattle-King County, Washington) and Canada (Ottawa and Toronto, Ontario; and Vancouver, British Columbia). Each incident was linked to a census tract; tracts were classified into quartiles of median household income.



A total of 9235 sudden cardiac arrests were included in the analysis. For all sites combined, the incidence of sudden cardiac arrestin the lowest socioeconomic quartile was nearly double that in the highest quartile (incidence rate ratio [IRR] 1.9, 95% confidence interval [CI] 1.8-2.0). This disparity was greater among people less than 65 years old (IRR 2.7, 95% CI 2.5-3.0) than among those 65 or older (IRR 1.3, 95% CI 1.2-1.4). After adjustment for study site and for population age structure of each census tract, the disparity across socioeconomic quartiles for all ages combined was greater in the United States (IRR 2.0, 95% CI 1.9-2.2) than in Canada (IRR 1.8, 95% CI 1.6-2.0) (p<0.001 for interaction).



The incidence of sudden cardiac arrest at home or at a residential institution was higher in poorer neighbourhoods of the US and Canadian sites studied, although the association was attenuated in Canada. The disparity across socioeconomic quartiles was greatest among people younger than 65. The association between socioeconomic status and incidence of sudden cardiac arrest merits consideration in the development of strategies to improve survival from sudden cardiac arrest, and possibly to identify opportunities for prevention.
Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY)

In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy.



Double-blind, 2-year study in which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28-erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage.



Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28-ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant-Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively.



No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients.
Purine Metabolism and Inhibition of Xanthine Oxidase in Severely Hypoxic Neonates Going onto Extracorporeal Membrane Oxygenation1

The effect of allopurinol to inhibit purine metabolism via the xanthine oxidase pathway in neonates with severe, progressive hypoxemia during rescue and reperfusion with extracorporeal membrane oxygenation (ECMO) was examined. Twenty-five term infants meeting ECMO criteria were randomized in a double-blinded, placebo-controlled trial. Fourteen did not receive allopurinol, whereas 11 were treated with 10 mg/kg after meeting criteria and before cannulation, in addition to a 20-mg/kg priming dose to the ECMO circuit. Infant plasma samples before cannulation, and at 15, 30, 60, and 90 min, and 3, 6, 9, and 12 h on bypass were analyzed (HPLC) for allopurinol, oxypurinol, hypoxanthine, xanthine, and uric acid concentrations. Urine samples were similarly evaluated for purine excretion. Hypoxanthine concentrations in isolated blood-primed ECMO circuits were separately measured. Hypoxanthine, xanthine, and uric acid levels were similar in both groups before ECMO. Hypoxanthine was higher in allopurinol-treated infants during the time of bypass studied (p = 0.022). Xanthine was also elevated (p < 0.001), and uric acid was decreased (p = 0.005) in infants receiving allopurinol. Similarly, urinary elimination of xanthine increased (p < 0.001), and of uric acid decreased(p = 0.04) in treated infants. No allopurinol toxicity was observed. Hypoxanthine concentrations were significantly higher in isolated ECMO circuits and increased over time during bypass (p < 0.001). This study demonstrates that allopurinol given before cannulation for and during ECMO significantly inhibits purine degradation and uric acid production, and may reduce the production of oxygen free radicals during reoxygenation and reperfusion of hypoxic neonates recovered on bypass.
Chemoprevention of colorectal neoplasia by estrogen: potential role of vitamin D activity.

Postmenopausal hormone replacement therapy lowers colon cancer incidence. In humans, the mechanism is unknown, but animal models suggest that it may involve activation of the vitamin D receptor (VDR) pathway. The aims of our study were to determine whether estrogen intervention affects global gene expression in rectal mucosal biopsies and whether vitamin D-related genes are affected. Estradiol was given to raise serum estradiol to premenopausal levels in 10 postmenopausal women under close nutritional control. Primary end points were expression of VDR, CYP24A1, CYP27B1, and E-cadherin in rectal mucosa by reverse transcription-PCR and examining response to estradiol by genome-wide arrays. Responses in gene expression in rectal biopsies to estrogen were determined in each subject individually and compared with a human estrogen response gene array database and a custom array in vitro-generated database. Cluster analysis showed that subjects maintained their overall gene expression profile and that interindividual differences were greater than intraindividual differences after intervention. Eight of 10 subjects showed significant enrichment in estrogen-responsive genes. Gene array group analysis showed activation of the VDR pathway and down-regulation of inflammatory and immune signaling pathways. Reverse transcription-PCR analysis showed significant up-regulation of VDR and E-cadherin, a downstream target of vitamin D action. These data suggest that the chemopreventive action of hormone replacement therapy on colon neoplasia results, at least in part, from changes in vitamin D activity. Evaluation of gene arrays is useful in chemopreventive intervention studies in small groups of subjects.
Aprotinin decreases reperfusion injury and allograft dysfunction in clinical lung transplantation.

Primary graft dysfunction caused by ischemia-reperfusion injury is one of the most frequent causes of early morbidity and death after lung transplantation. We hypothesized that the perioperative management with aprotinin decreases the incidence of allograft reperfusion injury and dysfunction after clinical lung transplantation.



Lung transplant databases of two transplant centers were used to investigate the incidence of severe post-transplant reperfusion injury (PTRI). We examined data of 142 patients who underwent either single lung (81) or bilateral sequential lung (61) transplantation for COPD, idiopathic pulmonary fibrosis, cystic fibrosis, and miscellaneous lung disorders between 1997 and 2000. Thirty patients were excluded due to heart-lung transplantation or lung transplantation for Eisenmenger's disease, re-transplantation, rejection, or deviation from the standardized triple immunosuppression protocol. The data of remaining 112 patients (control group, 64% single lung, 36% sequential bilateral lung transplants) were compared to the prospectively collected data of 59 lung transplant patients over the last 5 years. All of these 59 patients were managed perioperatively with aprotinin infusion. In addition, Euro-Collins-aprotinin procurement solution (Apt-EC group) was used for 50 donor lungs (58% single lung, 42% sequential bilateral lung transplants). Aprotinin in combination with low-potassium dextran (LPD) flush solution (Apt-LPD group) was used for the procurement of 34 lungs (59% single lung, 41% sequential bilateral lung transplants). The International Society of Heart and Lung Transplantation (ISHLT) grade III injury score was used for the diagnosis of severe PTRI, which is based on a PaO(2)-FIO(2) ratio of less than 200 mmHg.



Severe reperfusion injury grade III was observed in 18% of the control group. ECMO support was required in 25% of these patients. The associated mortality rate was 40%. Correlating factors for PTRI were donor age greater than 35 years (45%, p=0.01, mean age 38+/-8) and recipient pulmonary artery systolic pressure greater than 60 mmHg (48%, p<0.05). Lung graft ischemic times (231+/-14 min) and intraoperative techniques (cardiopulmonary bypass in 12%) were not associated with negative outcomes. Despite longer ischemic times (258+/-36 min and 317+/-85 min, respectively) and older donors (42+/-12 years and 46+/-12 years, respectively) in the aprotinin patient groups (Apt-EC and Apt-LPD group), the incidence of PTRI was markedly lower (6% and 9%, respectively). There was no mortality in the Apt-EC group and one patient died in the Apt-LPD group due to PTRI-induced graft failure.



Severe PTRI increased short-term morbidity and mortality. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia. The use of aprotinin in the perioperative patient management in lung transplantation had strong beneficial effects on the patient outcomes and decreased the incidence of post-transplant ischemia-reperfusion injury significantly.
Low numeracy is associated with increased odds of 30-day emergency department or hospital recidivism for patients with acute heart failure.

More than 25% of Medicare patients hospitalized for heart failure are readmitted within 30 days. The contributions of numeracy and health literacy to recidivism for patients with acute heart failure (AHF) are not known.



A cohort of patients with acute heart failure who presented to 4 emergency departments between January 2008 and September 2011. Research assistants administered subjective measures of numeracy and health literacy; 30-day follow-up was performed by phone interview. Recidivism was defined as any unplanned return to the emergency department or hospital within 30 days of the index emergency department visit for AHF. Multivariable logistic regression adjusting for patient age, sex, race, insurance status, hospital site, days eligible for recidivism, chronic kidney disease, abnormal hemoglobin, and low ejection fraction evaluated the relation between numeracy and health literacy with 30-day recidivism. Of the 709 patients included in the analysis, 390 (55%) had low numeracy skills and 258 (37%) had low literacy skills. Low numeracy was associated with increased odds of recidivism within 30 days (adjusted odds ratio, 1.41; 95% confidence interval, 1.00-1.98; P=0.048). For low health literacy, adjusted odds ratio of recidivism was 1.17 (95% confidence interval, 0.83-1.65; P=0.37).



Low numeracy was associated with greater odds of 30-day recidivism. Further investigation is warranted to determine whether addressing numeracy and health literacy may reduce 30-day recidivism for patients with acute heart failure.
Intervention to Lower Household Wood Smoke Exposure in Guatemala Reduces ST-Segment Depression on Electrocardiograms

A large body of evidence suggests that fine particulate matter (PM) air pollution is a cause of cardiovascular disease, but little is known in particular about the cardiovascular effects of indoor air pollution from household use of solid fuels in developing countries. RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects) was a randomized trial of a chimney woodstove that reduces wood smoke exposure.



We tested the hypotheses that the stove intervention, compared with open fire use, would reduce ST-segment depression and increase heart rate variability (HRV).



We used two complementary study designs: a) between-groups comparisons based on randomized stove assignment, and b) before-and-after comparisons within control subjects who used open fires during the trial and received chimney stoves after the trial. Electrocardiogram sessions that lasted 20 hr were repeated up to three times among 49 intervention and 70 control women 38-84 years of age, and 55 control subjects were also assessed after receiving stoves. HRV and ST-segment values were assessed for each 30-min period. ST-segment depression was defined as an average value below -1.00 mm. Personal fine PM [aerodynamic diameter ≤ 2.5 μm (PM₂.₅] exposures were measured for 24 hr before each electrocardiogram.



PM₂.₅ exposure means were 266 and 102 μg/m³ during the trial period in the control and intervention groups, respectively. During the trial, the stove intervention was associated with an odds ratio of 0.26 (95% confidence interval, 0.08-0.90) for ST-segment depression. We found similar associations with the before-and-after comparison. The intervention was not significantly associated with HRV.



The stove intervention was associated with reduced occurrence of nonspecific ST-segment depression, suggesting that household wood smoke exposures affect ventricular repolarization and potentially cardiovascular health.
Training effects of short bouts of stair climbing on cardiorespiratory fitness, blood lipids, and homocysteine in sedentary young women.

To study the training effects of eight weeks of stair climbing on Vo2max, blood lipids, and homocysteine in sedentary, but otherwise healthy young women.



Fifteen women (mean (SD) age 18.8 (0.7) years) were randomly assigned to control (n = 7) or stair climbing (n = 8) groups. Stair climbing was progressively increased from one ascent a day in week 1 to five ascents a day in weeks 7 and 8. Training took place five days a week on a public access staircase (199 steps), at a stepping rate of 90 steps a minute. Each ascent took about two minutes to complete. Subjects agreed not to change their diet or lifestyle over the experimental period.



Relative to controls, the stair climbing group displayed a 17.1% increase in Vo2max and a 7.7% reduction in low density lipoprotein cholesterol (p < 0.05) over the training period. No change occurred in total cholesterol, high density lipoprotein cholesterol, triglycerides, or homocysteine.



The study confirms that accumulating short bouts of stair climbing activity throughout the day can favourably alter important cardiovascular risk factors in previously sedentary young women. Such exercise may be easily incorporated into the working day and therefore should be promoted by public health guidelines.
Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats.

Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions.



Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti-Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms.



The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect.