Stock-outs of essential medicines among community health workers (CHWs) in low- and middle-income countries (LMICs): a systematic literature review of the extent, reasons, and consequences.

BACKGROUND: This paper explores the extent of community-level stock-out of essential medicines among community health workers (CHWs) in low- and middle-income countries (LMICs) and identifies the reasons for and consequences of essential medicine stock-outs. METHODS: A systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases were searched with a prespecified strategy and the grey literature examined, January 2006-March 2021. Papers containing information on (1) the percentage of CHWs stocked out or (2) reasons for stock-outs along the supply chain and consequences of stock-out were included and appraised for risk of bias. Outcomes were quantitative data on the extent of stock-out, summarized using descriptive statistics, and qualitative data regarding reasons for and consequences of stock-outs, analyzed using thematic content analysis and narrative synthesis. RESULTS: Two reviewers screened 1083 records; 78 evaluations were included. Over the last 15 years, CHWs experienced stock-outs of essential medicines nearly one third of the time and at a significantly (p < 0.01) higher rate than the health centers to which they are affiliated (28.93% [CI 95%: 28.79-29.07] vs 9.17% [CI 95%: 8.64-9.70], respectively). A comparison of the period 2006-2015 and 2016-2021 showed a significant (p < 0.01) increase in CHW stock-out level from 26.36% [CI 95%: 26.22-26.50] to 48.65% [CI 95%: 48.02-49.28] while that of health centers increased from 7.79% [95% CI 7.16-8.42] to 14.28% [95% CI 11.22-17.34]. Distribution barriers were the most cited reasons for stock-outs. Ultimately, patients were the most affected: stock-outs resulted in out-of-pocket expenses to buy unavailable medicines, poor adherence to medicine regimes, dissatisfaction, and low service utilization. CONCLUSIONS: Community-level stock-out of essential medicines constitutes a serious threat to achieving universal health coverage and equitable improvement of health outcomes. This paper suggests stock-outs are getting worse, and that there are particular barriers at the last mile. There is an urgent need to address the health and non-health system constraints that prevent the essential medicines procured for LMICs by international and national stakeholders from reaching the people who need them the most.

How to assure access of essential RMNCH medicines by looking at policy and systems factors: an analysis of countdown to 2015 countries.

BACKGROUND: In 2000, the Millennium Development Goals set targets for social achievements by 2015 including goals related to maternal and child health, with mixed success. Several initiatives supported these goals including assuring availability of appropriate medicines and commodities to meet health service targets. To reach the new Sustainable Development Goals by 2030, information is needed to address policy and systems factors to improve access to lifesaving commodities. METHODS: We compiled indicator data on 15 commodities related to reproductive, maternal, newborn, and child health (RMNCH) and analyzed them across 75 Countdown to 2015 countries from eight regions to identify problems with specific commodities and determinants of access. The determinants related to policy, regulatory environment, financing, pharmaceutical procurement and supply chain, and information systems. We mapped commodity information from four datasets from the World Health Organization and the United Nation's Commission on Life Saving Commodities creating a stoplight dashboard to illustrate countries' environment to assure access. We also developed a dashboard for policy and systems indicators for select countries. RESULTS: The commodities we identified as having the fewest barriers to access had been in use longer, including oral rehydration solution and oxytocin injection. Looking across the different systems and policy determinants of access, only Zimbabwe had all 15 commodities on both its essential medicines list and in its standard treatment guidelines, and only Cameroon and Zambia had at least one product registered for each commodity. Senegal alone procured all tracer commodities centrally in the previous year, and 70% of responding countries had costed plans for maternal, newborn, and child health. No country reported recent stock-outs of all the 15 commodities at the central level-countries always had some of the 15 commodities available; however, products with frequent stock-outs included misoprostol, calcium gluconate, penicillin injections, ceftriaxone, and amoxicillin dispersible tablets. CONCLUSIONS: This analysis highlights country deficiencies in policies and systems, such as incoherent policy guidelines, problems in product registration, lack of logistics data, and central-level stock-outs that may affect access to essential RMNCH commodities. To tackle these deficiencies, countries need to integrate commodity-related indicators into other health monitoring activities to improve service quality.

High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma.

In a search for genes specifically expressed in Reed-Sternberg (RS) cells of Hodgkin lymphoma (HL), we applied the serial analysis of gene expression (SAGE) technique on the HL-derived cell line DEV. Genes highly expressed in DEV were subjected to an RT-PCR analysis to confirm the SAGE results. For one of the genes, a high expression was observed in DEV and other HL-derived cell lines but not in non-Hodgkin lymphoma (NHL)-derived cell lines and normal controls, suggesting an HL-specific expression. This gene corresponds to the human BIC gene, a member of the noncoding mRNA-like molecules. RNA in situ hybridization (ISH) indicated an exclusive nucleolar localization of BIC transcripts in all RS cells in 91% of HL cases, including nodular lymphocyte predominance (NLP) HL and classical HL. Analyses of normal human tissues revealed BIC transcripts in only a small number of CD20-positive B-cells in lymph node and tonsil tissue, albeit at a much lower level compared to that of RS cells. BIC RT-PCR in the Burkitt lymphoma-derived cell line Ramos demonstrated a significant up-regulation upon cross-linking of the B-cell receptor (BcR). IkappaBalpha-mediated blocking of NF-kappaB translocation in Ramos did not effect the up-regulation of BIC expression upon BcR triggering, suggesting that activation of NF-kappaB is not involved in regulation of BIC expression. In summary, our data show that expression of BIC is specific for RS cells of HL. In normal tissue, BIC is expressed weakly in a minority of germinal center B cells. Expression of BIC can be modified/influenced by BcR triggering, indicating that BIC might play a role in the selection of B cells.

Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.

Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5; P<.001), although this was not significant on multivariate analysis (P=.11). Median hospital charges were 29,455 dollars for control subjects, 52,791 dollars for patients with MSSA SSI, and 92,363 dollars for patients with MRSA SSI (P<.001 for all group comparisons). Patients with MRSA SSI had a 1.19-fold increase in hospital charges (P=.03) and had mean attributable excess charges of 13,901 dollars per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.

Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections.

BACKGROUND: Bloodstream infections occurring in persons residing in the community, regardless of whether those persons have been receiving health care in an outpatient facility, have traditionally been categorized as community-acquired infections. OBJECTIVE: To develop a new classification scheme for bloodstream infections that distinguishes among community-acquired, health care-associated, and nosocomial infections. DESIGN: Prospective observational study. SETTING: One academic medical center and two community hospitals. PATIENTS: All adult patients admitted to the hospital with bloodstream infection. MEASUREMENTS: Demographic characteristics, living arrangements before hospitalization, comorbid medical conditions, factors predisposing to bloodstream infection, date of hospitalization, dates and number of positive blood cultures, results of microbiological susceptibility testing, dates of hospital discharge or death, and mortality rates at 3 to 6 months of follow-up. RESULTS: 504 patients with bloodstream infections were enrolled; 143 (28%) had community-acquired bloodstream infections, 186 (37%) had health care-associated bloodstream infections, and 175 (35%) had nosocomial bloodstream infections. Of the 186 patients with health care-associated bloodstream infection, 29 resided in a nursing home, 64 were receiving home health care, 78 were receiving intravenous or intravascular therapy at home or in a clinic, and 117 had been hospitalized in the 90 days before their bloodstream infection. Cancer was more common in patients with health care-associated or nosocomial bloodstream infection than in patients with community-acquired bloodstream infection. Intravascular devices were the most common source of health care-associated and nosocomial infections, and Staphylococcus aureus was the most frequent pathogen in these types of infections. Methicillin-resistant S. aureus occurred with similar frequency in the groups with health care-associated infection (52%) and nosocomial infection (61%) but was uncommon in the group with community-acquired bloodstream infection (14%) (P = 0.001). Mortality rate at follow-up was greater in patients with health care-associated infection (29% versus 16%; P = 0.019) or nosocomial infection (37% versus 16%; P < 0.001) than in patients with community-acquired infection. CONCLUSIONS: Health care-associated bloodstream infections are similar to nosocomial infections in terms of frequency of various comorbid conditions, source of infection, pathogens and their susceptibility patterns, and mortality rate at follow-up. A separate category for health care-associated bloodstream infections is justified, and this new category will have obvious implications for choices about empirical therapy and infection-control surveillance.

Postoperative bacteremia secondary to surgical site infection.

We evaluated all surgical site infections (SSI) and postoperative bacteremias secondary to SSI as part of an ongoing active surgical surveillance program at a community hospital. Among 40,191 surgical procedures, we identified 515 patients with SSI and 47 with postoperative bacteremia secondary to SSI. Four variables were examined as potential predictors for developing postoperative bacteremia secondary to an SSI: National Nosocomial Infections Surveillance risk index, abdominal surgery, surgical procedures with an implantable device, and the presence of Staphylococcus aureus in wounds. Of these 4 variables, only one, S. aureus isolated from a wound culture, was associated with an increased risk of developing postoperative bacteremia secondary to SSI. Patients with S. aureus isolated in either pure or mixed culture from SSI were more than twice as likely to have postoperative bacteremia secondary to SSI than were those without S. aureus wound infection.