nils-herrmann/clean_scirepeval huggingface dataset:
How Can Childbirth Care for the Rural Poor Be Improved? A Contribution from Spatial Modelling in Rural Tanzania

Maternal and perinatal mortality remain a challenge in resource-limited countries, particularly among the rural poor. To save lives at birth health facility delivery is recommended. However, increasing coverage of institutional deliveries may not translate into mortality reduction if shortage of qualified staff and lack of enabling working conditions affect quality of services. In Tanzania childbirth care is available in all facilities; yet maternal and newborn mortality are high. The study aimed to assess in a high facility density rural context whether a health system organization with fewer delivery sites is feasible in terms of population access.



Data on health facilities' location, staffing and delivery caseload were examined in Ludewa and Iringa Districts, Southern Tanzania. Geospatial raster and network analysis were performed to estimate access to obstetric services in walking time. The present geographical accessibility was compared to a theoretical scenario with a 40% reduction of delivery sites.



About half of first-line health facilities had insufficient staff to offer full-time obstetric services (45.7% in Iringa and 78.8% in Ludewa District). Yearly delivery caseload at first-line health facilities was low, with less than 100 deliveries in 48/70 and 43/52 facilities in Iringa and Ludewa District respectively. Wide geographical overlaps of facility catchment areas were observed. In Iringa 54% of the population was within 1-hour walking distance from the nearest facility and 87.8% within 2 hours, in Ludewa, the percentages were 39.9% and 82.3%. With a 40% reduction of delivery sites, approximately 80% of population will still be within 2 hours' walking time.



Our findings from spatial modelling in a high facility density context indicate that reducing delivery sites by 40% will decrease population access within 2 hours by 7%. Focused efforts on fewer delivery sites might assist strengthening delivery services in resource-limited settings.
Estimating Trends in the Proportion of Transmitted and Acquired HIV Drug Resistance in a Long Term Observational Cohort in Germany

We assessed trends in the proportion of transmitted (TDR) and acquired (ADR) HIV drug resistance and associated mutations between 2001 and 2011 in the German ClinSurv-HIV Drug Resistance Study.



The German ClinSurv-HIV Drug Resistance Study is a subset of the German ClinSurv-HIV Cohort. For the ClinSurv-HIV Drug Resistance Study all available sequences isolated from patients in five study centres of the long term observational ClinSurv-HIV Cohort were included. TDR was estimated using the first viral sequence of antiretroviral treatment (ART) naïve patients. One HIV sequence/patient/year of ART experienced patients was considered to estimate the proportion of ADR. Trends in the proportion of HIV drug resistance were calculated by logistic regression.



9,528 patients were included into the analysis. HIV-sequences of antiretroviral naïve and treatment experienced patients were available from 34% (3,267/9,528) of patients. The proportion of TDR over time was stable at 10.4% (95% CI 9.1-11.8; p for trend = 0.6; 2001-2011). The proportion of ADR among all treated patients was 16%, whereas it was high among those with available HIV genotypic resistance test (64%; 1,310/2,049 sequences; 95% CI 62-66) but declined significantly over time (OR 0.8; 95% CI 0.77-0.83; p for trend<0.001; 2001-2011). Viral load monitoring subsequent to resistance testing was performed in the majority of treated patients (96%) and most of them (67%) were treated successfully.



The proportion of TDR was stable in this study population. ADR declined significantly over time. This decline might have been influenced by broader resistance testing, resistance test guided therapy and the availability of more therapeutic options and not by a decline in the proportion of TDR within the study population.
Assisted partner notification services to augment HIV testing and linkage to care in Kenya: study protocol for a cluster randomized trial

HIV case-finding and linkage to care are critical for control of HIV transmission. In Kenya, >50% of seropositive individuals are unaware of their status. Assisted partner notification is a public health strategy that provides HIV testing to individuals with sexual exposure to HIV and are at risk of infection and disease. This parallel, cluster-randomized controlled trial will evaluate the effectiveness, cost-effectiveness, and feasibility of implementing HIV assisted partner notification services at HIV testing sites (clusters) in Kenya.



Eighteen sites were selected among health facilities in Kenya with well-established, high-volume HIV testing programs, to reflect diverse communities and health-care settings. Restricted randomization was used to balance site characteristics between study arms (n = 9 per arm). Sixty individuals testing HIV positive ('index partners') will be enrolled per site (inclusion criteria: ≥18 years, positive HIV test at a study site, willing to disclose sexual partners, and never enrolled for HIV care; exclusion criteria: pregnancy or high risk of intimate partner violence). Index partners provide names and contact information for all sexual partners in the past 3 years. At intervention sites, study staff immediately contact sexual partners to notify them of exposure, offer HIV testing, and link to care if HIV seropositive. At control sites, passive partner referral is performed according to national guidelines, and assisted partner notification is delayed by 6 weeks. Primary outcomes, assessed 6 weeks after index partner enrollment and analyzed at the cluster level, are the number of partners accepting HIV testing and number of HIV infections diagnosed and linked to care per index partner. Secondary outcomes are the incremental cost-effectiveness of partner notification and the costs of identifying >1 partner per index case. Participants are closely monitored for adverse outcomes, particularly intimate partner violence. The study is unblinded due to practical limitations.



This rigorously designed trial will inform policy decisions regarding implementation of HIV partner notification services in Kenya, with possible application to other parts of sub-Saharan Africa. Examination of effectiveness and cost-effectiveness in diverse settings will enable targeted application and define best practices.
Reproducibility of a 3-dimensional gyroscope in measuring shoulder anteflexion and abduction

Few studies have investigated the use of a 3-dimensional gyroscope for measuring the range of motion (ROM) in the impaired shoulder. Reproducibility of digital inclinometer and visual estimation is poor. This study aims to investigate the reproducibility of a tri axial gyroscope in measurement of anteflexion, abduction and related rotations in the impaired shoulder.



Fifty-eight patients with either subacromial impingement (27) or osteoarthritis of the shoulder (31) participated. Active anteflexion, abduction and related rotations were measured with a tri axial gyroscope according to a test retest protocol. Severity of shoulder impairment and patient perceived pain were assessed by the Disability of Arm Shoulder and Hand score (DASH) and the Visual Analogue Scale (VAS). VAS scores were recorded before and after testing.



In two out of three hospitals patients with osteoarthritis (n = 31) were measured, in the third hospital patients with subacromial impingement (n = 27).There were significant differences among hospitals for the VAS and DASH scores measured before and after testing. The mean differences between the test and retest means for anteflexion were -6 degrees (affected side), 9 (contralateral side) and for abduction 15 degrees (affected side) and 10 degrees (contralateral side).Bland & Altman plots showed that the confidence intervals for the mean differences fall within -6 up to 15 degrees, individual test - retest differences could exceed these limits.A simulation according to 'Generalizability Theory' produces very good coefficients for anteflexion and related rotation as a comprehensive measure of reproducibility. Optimal reproducibility is achieved with 2 repetitions for anteflexion.



Measurements were influenced by patient perceived pain. Differences in VAS and DASH might be explained by different underlying pathology. These differences in shoulder pathology however did not alter the reproducibility of testing. The use of a tri axial gyroscope is a simple non invasive and reproducible method for the recording of shoulder anteflexion and abduction. Movements have to be repeated twice for reproducible results.
Total pineal endocrine substitution therapy (TPEST) as a new neuroendocrine palliative treatment of untreatable metastatic solid tumor patients: a phase II study.

It is known since many years that the pineal gland plays an anticancer role, and melatonin (MLT), the most investigated pineal hormone, has been proven to exert antitumor activity. However, MLT would not be the only hormone responsible for the antitumor action of the pineal gland. In fact, recent advances in the pineal investigations have shown that pineal indoles other than MLT may also exert anticancer activity, namely the three main indoles, consisting of 5-methoxytriptamine (5-MTT), 5-methoxytryptophol (5-MTP) and 5-methoxy-indole acetic acid (5-MIA). Cancer progression has appeared to be associated with a concomitant decline in the pineal endocrine function. Therefore, the replacement of a complete pineal function in the advanced cancer patients would require the exogenous administration of the overall four pineal indoles. Several clinical studies have shown that MLT alone at pharmacological doses may induce a control of the neoplastic progression in about 30% of untreatable metastatic solid tumor patients. The present study was performed in an attempt to evaluate the therapeutic of a total pineal endocrine substitution therapy with its four indole hormones in cancer patients, for whom no other conventional therapy was available.



The study included 14 metastatic solid tumor patients, who had failed to respond to the conventional anticancer therapies. The pineal indoles were given orally according to a schedule elaborated in an attempt to reproduce their physiological circadian secretion during the daily photoperiod. MLT was given at 20 mg/day during the night, whereas the other indoles were given at 1 mg/day, by administering 5-MIA in the morning, 5-MTP at noon and 5-MTT in the afternoon.



A disease-control was achieved in 9/14 (64%) patients, consisting of partial response (PR) in one patient and stable disease (SD) in the other 8 patients. The median time of disease-control (PR + SD) was 6 months (range: 4-10).



This preliminary study shows that a total pineal endocrine replacement therapy by an exogenous administration of the overall four pineal indoles may induce a disease-control in about 60% of untreatable metastatic solid tumor patients. Then, these results would be clearly superior with respect to those described with MLT alone, by confirming in humans that MLT is not the only hormone responsible for the anticancer property of the pineal gland. Since Cartesius was the first author who suggested the fundamental role of the pineal in the connection between consciousness and biological life, this therapy could be defined as a Cartesian therapy.
β-Blockers in patients with intermittent claudication and arterial hypertension: results from the nebivolol or metoprolol in arterial occlusive disease trial.

The use of β-receptor blockers in peripheral arterial disease is controversial for their impact on vasomotor tone. The β-blocker nebivolol possesses vasodilating, endothelium-dependent, NO-releasing properties that might be beneficial in peripheral arterial disease. The aim of the study was to evaluate the effects and tolerability of nebivolol in comparison with metoprolol in these patients. A total of 128 patients with intermittent claudication and essential hypertension were included and double-blind randomized to receive 5 mg of nebivolol (N=65) or 95 mg of metoprolol (N=63) once daily. End points were changes in ankle-brachial index, initial and absolute claudication distance, endothelial function assessed by flow-mediated dilatation of the brachial artery, blood pressure, and quality of life using the claudication scale questionnaire. End point analysis was possible in 109 patients (85.2%). After the 48-week treatment period, ankle-brachial index and absolute claudication distance improved significantly in both patient groups (P<0.05 for both), with no difference across treatments. A significant increase of initial claudication distance was found in the nebivolol group. Adjusted mean change of initial claudication distance was 33.9% after nebivolol (P=0.003) and 16.6% after metoprolol (P=0.12) treatment. Quality of life was not influenced by either treatment, and there was no relevant change in flow-mediated dilatation in patients treated with nebivolol or metoprolol (P=0.16). Both drugs were equally effective in lowering blood pressure. In conclusion, β-blocker therapy was well tolerated in patients with intermittent claudication and arterial hypertension during a treatment period of ≈1 year. In the direct comparison, there was no significant difference between nebivolol and metoprolol.
Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.

Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.



A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).



Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.



We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
Comparing two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the hypofractionated treatment of high-risk prostate cancer

To compare two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the setting of hypofractionated high-risk prostate cancer treatment.



3DCRT and dIMRT/Helical Tomotherapy(HT) planning with 10 CT datasets was undertaken to deliver 68 Gy in 25 fractions (prostate) and simultaneously delivering 45 Gy in 25 fractions (pelvic lymph node targets) in a single phase. The paradigms of pelvic vessel targeting (iliac vessels with margin are used to target pelvic nodes) and conformal normal tissue avoidance (treated soft tissues of the pelvis while limiting dose to identified pelvic critical structures) were assessed compared to 3DCRT controls. Both dIMRT/HT and 3DCRT solutions were compared to each other using repeated measures ANOVA and post-hoc paired t-tests.



When compared to conformal pelvic vessel targeting, conformal normal tissue avoidance delivered more homogenous PTV delivery (2/2 t-test comparisons; p < 0.001), similar nodal coverage (8/8 t-test comparisons; p = ns), higher and more homogenous pelvic tissue dose (6/6 t-test comparisons; p < 0.03), at the cost of slightly higher critical structure dose (Ddose, 1-3 Gy over 5/10 dose points; p < 0.03). The dIMRT/HT approaches were superior to 3DCRT in sparing organs at risk (22/24 t-test comparisons; p < 0.05).



dIMRT/HT nodal and pelvic targeting is superior to 3DCRT in dose delivery and critical structure sparing in the setting of hypofractionation for high-risk prostate cancer. The pelvic targeting paradigm is a potential solution to deliver highly conformal pelvic radiation treatment in the setting of nodal location uncertainty in prostate cancer and other pelvic malignancies.
Feasibility of two dose-dense FEC regimens with growth factor support for adjuvant therapy in patients with early breast cancer: results from a randomised study of the Central European Cooperative Oncology Group (CECOG)

Addition of epirubicin to adjuvant chemotherapy can provide important benefits for patients with early breast cancer, but the optimal dose remains unclear. Further improvements can be achieved with dose-dense regimens, but densification of fluorouracil/epirubicin/cyclophosphamide (FEC) has proved difficult, with FEC60 providing little benefit over standard chemotherapy and FEC100 associated with toxicity. We investigated the feasibility of two intermediate dose-dense FEC regimens. Patients were randomised to six cycles of FEC75 or FEC90, with all three drugs given on day 1 of each 14-day cycle. Patients also received pegfilgrastim 6 mg as a single subcutaneous injection on day 2 of each cycle. The primary efficacy endpoint was the proportion of subjects receiving ≥85% relative dose intensity and was achieved by 96% and 88% of patients in the FEC75 and FEC90 arms, respectively. Of 147 FEC75 infusions, 4.1% were delayed, while 9.8% of 143 FEC90 infusions were delayed. The most common reasons for delay were adverse events and personal/logistical reasons. One dose reduction occurred during the study (FEC90), related to diarrhoea. Grade 3–4 haematological toxicities were reported in two patients in the FEC90 arm. There were no incidences of febrile neutropenia during the study. The most common adverse events were increases in liver enzymes and gastrointestinal events; no event resulted in discontinuation. Only one patient (FEC90) experienced serious adverse events (vomiting and throat oedema). In conclusion, dose-dense FEC75 and FEC90 are feasible with pegfilgrastim support. These regimens are associated with a very low risk of Grade 3–4 toxicity.
Antenatal steroid exposure and outcomes of very premature infants: a regional cohort study.

To compare mortality, short-term morbidity and long-term neurodevelopmental outcomes of <29 week premature infants with antenatal steroid exposure (none, incomplete and complete).



Multicentre retrospective cohort study, within a geographically defined area in Australia served by a network of 10 neonatal intensive care units (NICUs), of infants <29 weeks gestational age, admitted to NICUs between 1998 and 2004. Outcome measures included hospital survival, perinatal complications and functional disability at 2-3 years follow-up.



2549 neonates were included; 319 (12.5%) received no exposure to steroids. Hospital mortality (OR 0.59, 95% CI 0.45 to 0.76, p<0.001, intraventricular haemorrhage (IVH) (OR 0.58, 95% CI 0.42 to 0.81, p=0.001) and necrotising entercolitis (NEC) (OR 0.62, 95% CI 0.42 to 0.91, p=0.018) was less likely in infants with any steroid exposure. Any steroid exposure was associated with less need for surfactant (OR 0.41, 95% CI 0.30 to 0.57, p<0.001) and mechanical ventilation (OR 0.30, 95% CI 0.17 to 0.52, p<0.001). Subgroup analyses demonstrated differences in outcomes only with complete steroid coverage and not with incomplete coverage. Survival benefit and reduction in the incidence of severe IVH was evident from 24 to 28 weeks. Long-term neurodevelopmental data available for 1473 survivors showed no significant difference in outcomes with steroid exposure after multivariate analysis.



Exposure to a complete course of antenatal steroids is associated with higher infant survival rates, lower rates of severe IVH and NEC compared to an incomplete course or no exposure. Any exposure to steroids reduces the risk of moderate cerebral palsy, however, long-term neurodevelopmental outcome may not be affected by steroid exposure.
Superficial femoral artery plaque, the ankle-brachial index, and leg symptoms in peripheral arterial disease: the walking and leg circulation study (WALCS) III.

The clinical significance of magnetic resonance-imaged plaque characteristics in the superficial femoral artery (SFA) is not well established. We studied associations of the ankle-brachial index (ABI) and leg symptoms with MRI-measured plaque area and percent lumen area in the SFA in participants with and without lower-extremity peripheral arterial disease (PAD).



Four hundred twenty-seven participants (393 with PAD) underwent plaque imaging of the first 30 mm of the SFA. Twelve 2.5-mm cross-sectional images of the SFA were obtained. Outcomes were normalized plaque area, adjusted for artery size (0 to 1 scale, 1=greatest plaque), and lumen area, expressed as a percent of the total artery area. Adjusting for age, sex, race, smoking, statins, cholesterol, and other covariates, lower ABI values were associated with higher normalized mean plaque area (ABI <0.50:0.79; ABI 0.50 to 0.69:0.73; ABI 0.70 to 0.89:0.65; ABI 0.90 to 0.99:0.62; ABI 1.00 to 1.09:0.48; ABI 1.10 to 1.30:0.47 (P trend <0.001)) and smaller mean percent lumen area (P trend <0.001). Compared with PAD participants with intermittent claudication, asymptomatic PAD participants had lower normalized mean plaque area (0.72 versus 0.65, P=0.005) and larger mean percent lumen area (0.30 versus 0.36, P=0.01), adjusting for the ABI and other confounders.



Lower ABI values are associated with greater MRI-measured plaque burden and smaller lumen area in the first 30 mm of the SFA. Compared with PAD participants with claudication, asymptomatic PAD participants have smaller plaque area and larger lumen area in the SFA.