Alicen B. Spaulding

Background: Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic. Methods: The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories. Results: Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0. Conclusion: Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.

BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute.

BACKGROUND: The integration of HIV/AIDS and maternal, neonatal, child health and nutrition services (MNCHN), including family planning (FP) is recognized as a key strategy to reduce maternal and child mortality and control the HIV/AIDS epidemic. However, limited evidence exists on the effectiveness of service integration. OBJECTIVES: To evaluate the impact of integrating MNCHN-FP and HIV/AIDS services on health, behavioral, and economic outcomes and to identify research gaps. SEARCH METHODS: Using the Cochrane Collaboration's validated search strategies for identifying reports of HIV interventions, along with appropriate keywords and MeSH terms, we searched a range of electronic databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE (via PubMed), and Web of Science / Web of Social Science. The date range was from 01 January 1990 to 15 October 2010. There were no limits to language. SELECTION CRITERIA: Included studies were published in peer-reviewed journals, and provided intervention evaluation data (pre-post or multi-arm study design).The interventions described were organizational strategies or change, process modifications or introductions of technologies aimed at integrating MNCHN-FP and HIV/AIDS service delivery. DATA COLLECTION AND ANALYSIS: We identified 10,619 citations from the electronic database searches and 101 citations from hand searching, cross-reference searching and interpersonal communication. After initial screenings for relevance by pairs of authors working independently, a total of 121 full-text articles were obtained for closer examination. MAIN RESULTS: Twenty peer-reviewed articles representing 19 interventions met inclusion criteria. There were no randomized controlled trials. One study utilized a stepped wedge design, while the rest were non-randomized trials, cohort studies, time series studies, cross-sectional studies, serial cross-sectional studies, and before-after studies. It was not possible to perform meta-analysis. Risk of bias was generally high. We found high between-study heterogeneity in terms of intervention types, study objectives, settings and designs, and reported outcomes. Most studies integrated FP with HIV testing (n=7) or HIV care and treatment (n=4). Overall, HIV and MNCHN-FP service integration was found to be feasible across a variety of integration models, settings and target populations. Nearly all studies reported positive post-integration effects on key outcomes including contraceptive use, antiretroviral therapy initiation in pregnancy, HIV testing, and quality of services. AUTHORS' CONCLUSIONS: This systematic review's findings show that integrated HIV/AIDS and MNCHN-FP services are feasible to implement and show promise towards improving a variety of health and behavioral outcomes. However, significant evidence gaps remain. Rigorous research comparing outcomes of integrated with non-integrated services, including cost, cost-effectiveness, and health outcomes such as HIV and STI incidence, morbidity and mortality are greatly needed to inform programs and policy.

BACKGROUND: The international community agrees that the Millennium Development Goals will not be achieved without ensuring universal access to both sexual and reproductive health (SRH) services and HIV/AIDS prevention, treatment, care and support. Recently, there has been increasing awareness and discussion of the possible benefits of linkages between SRH and HIV programmes at the policy, systems and service delivery levels. However, the evidence for the efficacy of these linkages has not been systematically assessed. METHODS: We conducted a systematic review of the evidence for interventions linking SRH and HIV. Structured methods were employed for searching, screening and data extraction. Studies from 1990 to 2007 reporting pre-post or multi-arm evaluation data from SRH-HIV linkage interventions were included. Study design rigour was scored on a nine-point scale. Unpublished programme reports were gathered as "promising practices". RESULTS: Of more than 50,000 citations identified, 185 studies were included in the review and 35 were analyzed. These studies had heterogeneous interventions, populations, objectives, study designs, rigour and measured outcomes. SRH-HIV linkage interventions were generally considered beneficial and feasible. The majority of studies showed improvements in all outcomes measured. While there were some mixed results, there were very few negative findings. Generally, positive effects were shown for key outcomes, including HIV incidence, sexually transmitted infection incidence, condom use, contraceptive use, uptake of HIV testing and quality of services. Promising practices (n = 23) tended to evaluate more recent and more comprehensive programmes. Factors promoting effective linkages included stakeholder involvement, capacity building, positive staff attitudes, non-stigmatizing services, and engagement of key populations. CONCLUSIONS: Existing evidence provides support for linkages, although significant gaps in the literature remain. Policy makers, programme managers and researchers should continue to advocate for, support, implement and rigorously evaluate SRH and HIV linkages at the policy, systems and service levels.

RATIONALE: Nontuberculous mycobacteria are an important cause of morbidity in the United States, although patient outcomes vary greatly by species. Currently, nationally representative data on the distribution of mycobacterial species from clinical isolates are limited. OBJECTIVES: Using a national hospitalization database capturing microbiologic data for nearly 6 million patient encounters, we describe the geographic distribution of, and patient demographic features associated with, clinical mycobacterial isolates in the United States. METHODS: Linked demographic and microbiologic data from the Premier Healthcare Database were extracted for all patient encounters from 2009 to 2013. Patients with at least one positive potentially pathogenic nontuberculous mycobacterial culture were identified as cases. The period prevalence was calculated, and patient-, encounter-, and hospital-level factors were analyzed. Regional differences in species distribution were analyzed; a subanalysis was conducted among patients with International Classification of Diseases, Ninth Revision, codes for pulmonary nontuberculous mycobacterial disease. Significant differences were assessed (P < 0.05). RESULTS: Of 5,928,830 unique patients included during the 5-year study period, 7,812 (0.13%) had at least one positive nontuberculous mycobacterial culture. The mean age of cases was 64 years (range, <1-89 yr), and most were female (52%) and white (70%). Hospitals with cases were more often labeled "urban" (96%), "teaching" (56%), and had at least 500 beds (78%). Species distribution differed significantly by geographic area. Mycobacterium avium complex ranged from 61 to 91% of isolates and were most frequent in the South and Northeast regions; M. abscessus/M. chelonae ranged from 2 to 18% of isolates and were most frequent in the West; and other species, including M. fortuitum and M. kansasii, ranged from 7 to 26% and were also most frequent in the West. CONCLUSIONS: Significant geographic variation exists in the distribution of nontuberculous mycobacterial species in the United States. Whereas M. avium complex was the most common species isolated in the South, M. abscessus/M. chelonae was proportionately higher in the West. Greater clinical awareness in regions with increased levels of harder-to-treat mycobacteria are needed, given differences in treatment options and implications for patient outcomes.