2 research outputs found
Health System Capacity and Access Barriers to Diagnosis and Treatment of CVD and Diabetes in Nepal
Background: Universal access to essential medicines and routine diagnostics is required to combat the growing burden of cardiovascular disease (CVD) and diabetes. Evaluating health systems and various access dimensions – availability, affordability, accessibility, acceptability, and quality – is crucial yet rarely performed, especially in low- and middle-income countries. Objective: To evaluate health system capacity and barriers in accessing diagnostics and essential medicines for CVD and diabetes in Nepal. Methods: We conducted a WHO/HAI nationally-representative survey in 45 health-facilities (public sector: 11; private sector: 34) in Nepal to collect availability and price data for 21 essential medicines for treating CVD and diabetes, during May–July 2017. Data for 13 routine diagnostics were obtained in 12 health facilities. Medicines were considered unaffordable if the lowest paid worker spends >1 day’s wage to purchase a monthly supply. To evaluate accessibility, we conducted facility exit interviews among 636 CVD patients. Accessibility (e.g., private-public health facility mix, travel to hospital/pharmacy) and acceptability (i.e. Nepal’s adoption of WHO Essential Medicine List, and patient medication adherence) were summarized using descriptive statistics, and we conducted a systematic review of relevant literature. We did not evaluate medicine quality. Results: We found that mean availability of generic medicines is low (<50%) in both public and private sectors, and less than one-third medicines met WHO’s availability target (80%). Mean (SD) availability of diagnostics was 73.1% (26.8%). Essential medicines appear locally unaffordable. On average, the lowest-paid worker would spend 1.03 (public sector) and 1.26 (private sector) days’ wages to purchase a monthly medicine supply. For a person undergoing CVD secondary-prevention interventions in the private sector, the associated expenditure would be 7.5–11.2% of monthly household income. Exit interviews suggest that a long/expensive commute to health facilities and poor medicine affordability constrain access. Conclusions: This study highlights critical gaps in Nepal’s health system capacity to offer basic health services to CVD and diabetes patients, owing to low availability and poor affordability and accessibility. Research and policy initiatives are needed to ensure uninterrupted supply of affordable essential medicines and diagnostics
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Prevalence and Predictors of Loss of Wild Type BRCA1 in Estrogen Receptor Positive and Negative BRCA1-Associated Breast Cancers
Introduction: The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that develop in BRCA1 carriers are ER-positive (ER+); these cancers are more likely to develop as BRCA1 carriers age, suggesting that they may be incidental and unrelated to BRCA1 deficiency. The purpose of this study was to compare the prevalence of loss of heterozygosity due to loss of wild type (wt) BRCA1 in ER+ and ER- breast cancers that have occurred in BRCA1 carriers and to determine whether age at diagnosis or any pathologic features or biomarkers predict for loss of wt BRCA1 in these breast cancers. Methods: Relative amounts of mutated and wt BRCA1 DNA were measured by quantitative polymerase chain reaction performed on laser capture microdissected cancer cells from 42 ER+ and 35 ER- invasive breast cancers that developed in BRCA1 carriers. BRCA1 gene methylation was determined on all cancers in which sufficient DNA was available. Immunostains for cytokeratins (CK) 5/6, 14, 8 and 18, epidermal growth factor receptor and p53 were performed on paraffin sections from tissue microarrays containing these cancers. Results: Loss of wt BRCA1 was equally frequent in ER+ and ER- BRCA1-associated cancers (81.0% vs 88.6%, respectively; P = 0.53). One of nine cancers tested that retained wt BRCA1 demonstrated BRCA1 gene methylation. Age at diagnosis was not significantly different between first invasive ER+ BRCA1 breast cancers with and without loss of wt BRCA1 (mean age 45.2 years vs 50.1 years, respectively; P = 0.51). ER+ BRCA1 cancers that retained wt BRCA1 were significantly more likely than those that lost wt BRCA1 to have a low mitotic rate (odds ratio (OR), 5.16; 95% CI, 1.91 to ∞). BRCA1 cancers with loss of wt BRCA1 were more likely to express basal cytokeratins CK 5/6 or 14 (OR 4.7; 95% CI, 1.85 to ∞). Conclusions: We found no difference in the prevalence of loss of wt BRCA1 between ER+ and ER- invasive BRCA1-associated breast cancers. Our findings suggest that many of the newer therapies for BRCA1 breast cancers designed to exploit the BRCA1 deficiency in these cancers may also be effective in ER+ cancers that develop in this population