Perspectives on reproductive healthcare delivered through a basic package of health services in Afghanistan: a qualitative study.

BACKGROUND: Contracting-out non-state providers to deliver a minimum package of essential health services is an increasingly common health service delivery mechanism in conflict-affected settings, where government capacity and resources are particularly constrained. Afghanistan, the longest-running example of Basic Package of Health Services (BPHS) contracting in a conflict-affected setting, enables study of how implementation of a national intervention influences access to prioritised health services. This study explores stakeholder perspectives of sexual and reproductive health (SRH) services delivered through the BPHS in Afghanistan, using Bamyan Province as a case study. METHODS: Twenty-six in-depth interviews were conducted with health-system practitioners (e.g. policy/regulatory, middle management, frontline providers) and four focus groups with service-users. Inductive thematic coding used the WHO Health System Framework categories (i.e. service delivery, workforce, medicines, information, financing, stewardship), while allowing for emergent themes. RESULTS: Improvements were noted by respondents in all health-system components discussed, with significant improvements identified in service coverage and workforce, particularly improved gender balance, numbers, training, and standardisation. Despite improvements, remaining weaknesses included service access and usage - especially in remote areas, staff retention, workload, and community accountability. CONCLUSIONS: By including perspectives on SRH service provision and BPHS contracting across health-system components and levels, this study contributes to broader debates on the effects of contracting on perceptions and experiences among practitioners and service-users in conflict-affected countries

Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.</p> <p>Methods</p> <p>114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV₁63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue⁺) area (%), proliferating (Ki-67⁺) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.</p> <p>Results</p> <p>Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).</p> <p>Conclusion</p> <p>Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).</p> <p>Trial registration</p> <p>NCT00158847</p

Impact of ≥ 0.1-mm free resection margins on local intramural residual cancer after local excision of T1 colorectal cancer

Background and study aims  A free resection margin (FRM) > 1 mm after local excision of a T1 colorectal cancer (CRC) is known to be associated with a low risk of local intramural residual cancer (LIRC). The risk is unclear, however, for FRMs between 0.1 to 1 mm. This study evaluated the risk of LIRC after local excision of T1 CRC with FRMs between 0.1 and 1 mm in the absence of lymphovascular invasion (LVI), poor differentiation and high-grade tumor budding (Bd2-3). Patients and methods  Data from all consecutive patients with local excision of T1 CRC between 2014 and 2017 were collected from 11 hospitals. Patients with a FRM ≥ 0.1 mm without LVI and poor differentiation were included. The main outcome was risk of LIRC (composite of residual cancer in the local excision scar in adjuvant resection specimens or local recurrence during follow-up). Tumor budding was also assessed for cases with a FRM between 0.1 and 1mm. Results  A total of 171 patients with a FRM between 0.1 and 1 mm and 351 patients with a FRM > 1 mm were included. LIRC occurred in five patients (2.9 %; 95 % confidence interval [CI] 1.0-6.7 %) and two patients (0.6 %; 95 % CI 0.1-2.1 %), respectively. Assessment of tumor budding showed Bd2-3 in 80 % of cases with LIRC and in 16 % of control cases. Accordingly, in patients with a FRM between 0.1 and 1 mm without Bd2-3, LIRC was detected in one patient (0.8%; 95 % CI 0.1-4.4 %). Conclusions  In this study, risks of LIRC were comparable for FRMs between 0.1 and 1 mm and > 1 mm in the absence of other histological risk factors

Methods for health surveys in difficult settings: charting progress, moving forward

Abstract Health surveys are a very important component of the epidemiology toolbox, and play a critical role in gauging population health, especially in developing countries. Research on health survey methods, however, is sparse. In particular, current sampling methods are not well adapted for certain 'difficult' settings, such as emergencies, remote regions without easily available sampling frames, hidden and vulnerable population groups, urban slums and populations living under strong political pressure. This special issue of Emerging Themes in Epidemiology is entirely devoted to survey methods in such settings, and builds upon a successful conference in London highlighting problems with current approaches and possible ways forward. Greater investment in research on health survey methods is needed and will have beneficial effects for populations in need.</jats:p

Modelling of early viral kinetics and pegylated interferon-α2b pharmacokinetics in patients with HBeAg-positive chronic hepatitis B

Background: Pegylated interferon α2b (PEG-IFN-α2b) is effective for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, although its mechanism of action remains unclear. HBeAg loss is achieved in 36% of patients after one year of PEG-IFN-α2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-α2b monotherapy. Methods: Early pharmacokinetics and viral kinetics were analysed in patients treated for 52 weeks with PEG-IFN-α2b with or without lamivudine. Results: After 4 weeks of treatment, there was a median viral decline of 2.94 log 10 copies/ml in those treated with PEG-IFN-α2b and lamivudine and only 0.45 log10 copies/ml in the PEG-IFN-α2b monotherapy group. Peak PEG-IFN-α2b levels were reached approximately one day after administration and subsequently declined exponentially, consistent with a viral load rebound near to baseline levels at the end of the dosing period in most patients receiving PEG-IFN-α2b monotherapy. Modelling of pharmacokinetics and viral kinetics data in this group revealed that viral load was minimal 3.6 days after PEG-IFN-α2b administration, the mean maximal and mean antiviral effectiveness was 70% and 48% with a mean infected cell loss rate of 0.07 per day, while no significant biphasic decline was observed. Conclusions: PEG-IFN-α2b induces a sustained response in a considerable number of patients despite limited direct antiviral activity during the first weeks of antiviral therapy.</p

Modelling of early viral kinetics and pegylated interferon-α2b pharmacokinetics in patients with HBeAg-positive chronic hepatitis B

Background: Pegylated interferon α2b (PEG-IFN-α2b) is effective for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, although its mechanism of action remains unclear. HBeAg loss is achieved in 36% of patients after one year of PEG-IFN-α2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-α2b monotherapy. Methods: Early pharmacokinetics and viral kinetics were analysed in patients treated for 52 weeks with PEG-IFN-α2b with or without lamivudine. Results: After 4 weeks of treatment, there was a median viral decline of 2.94 log 10 copies/ml in those treated with PEG-IFN-α2b and lamivudine and only 0.45 log10 copies/ml in the PEG-IFN-α2b monotherapy group. Peak PEG-IFN-α2b levels were reached approximately one day after administration and subsequently declined exponentially, consistent with a viral load rebound near to baseline levels at the end of the dosing period in most patients receiving PEG-IFN-α2b monotherapy. Modelling of pharmacokinetics and viral kinetics data in this group revealed that viral load was minimal 3.6 days after PEG-IFN-α2b administration, the mean maximal and mean antiviral effectiveness was 70% and 48% with a mean infected cell loss rate of 0.07 per day, while no significant biphasic decline was observed. Conclusions: PEG-IFN-α2b induces a sustained response in a considerable number of patients despite limited direct antiviral activity during the first weeks of antiviral therapy.</p

Modelling of early viral kinetics and pegylated interferon-alpha 2b pharmacokinetics in patients with HBeAg-positive chronic hepatitis B

Background: Pegylated interferon alpha 2b (PEG-IFN-alpha 2b) is effective for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, although its mechanism of action remains unclear. HBeAg loss is achieved in 36% of patients after one year of PEG-IFN-a2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-alpha 2b monotherapy

Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease: A randomized trial

Background: Inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD). Objective: To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD. Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847) Setting: 2 university medical centers in The Netherlands. Patients: 114 steroid-naive current or former smokers with moderate to severe COPD. Measurements: Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months. Intervention: Random assignment by minimization method to receive fluticasone propionate, 500 μg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 μg twice daily, and salmeterol, 50 μg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29). Results: 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3+ cells (-55% [95% CI, -74% to -22%]; P - 0.004), CD4- cells (-78% [CI, -88% to 60%]; P < 0.001), CD8+ cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to -2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV1 decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3+ cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV1 level. Limitations: The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months. Conclusion: ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects. Primary Funding Source: Netherlands Organization for Scientific Research, Netherlands Asthma Foundation, GlaxoSmithKline of The Netherlands, University Medical Center Groningen, and Leiden University Medical Center