Emily P. Hyle

Diagnostic point-of-care tests in resource-limited settings

The aim of diagnostic point-of-care testing is to minimise the time to obtain a test result, thereby allowing clinicians and patients to make a quick clinical decision. Because point-of-care tests are used in resource-limited settings, the benefits need to outweigh the costs. To optimise point-of-care testing in resource-limited settings, diagnostic tests need rigorous assessments focused on relevant clinical outcomes and operational costs, which differ from assessments of conventional diagnostic tests. We reviewed published studies on point-of-care testing in resource-limited settings, and found no clearly defined metric for the clinical usefulness of point-of-care testing. Therefore, we propose a framework for the assessment of point-of-care tests, and suggest and define the term test efficacy to describe the ability of a diagnostic test to support a clinical decision within its operational context. We also propose revised criteria for an ideal diagnostic point-of-care test in resource-limited settings. Through systematic assessments, comparisons between centralised testing and novel point-of-care technologies can be more formalised, and health officials can better establish which point-of-care technologies represent valuable additions to their clinical programmes.

Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study

OBJECTIVE To investigate the role of estrogen deprivation and replacement in amenorrheic and nonamenorrheic dancers on hormone therapy and calcium. DESIGN Clinical, placebo-controlled, randomized trial study.Healthy volunteers in an academic research environment. PATIENT(S) Fifty-five dancers (mean age: 22.0 +/- 4.6, age at menarche: 14.7 +/- 2.3 years), including 24 amenorrheics. INTERVENTION(S) Amenorrheics were randomized in a controlled trial to receive placebo or Premarin, 0.625 mg for 25 days monthly, with Provera, 10 mg, for 10 of these 25 days (hormone therapy) for 2 years. These women were compared to normally menstruating controls. The study participants also received 1250 mg of calcium per day. MAIN OUTCOME MEASURE(S) Bone mineral density (BMD) measured at the foot, wrist, and lumbar spine. Our overall results showed no difference in BMD between the treated or placebo groups, indicating that hormone therapy did not change or normalize BMD when compared to normals. Five patients (all on placebo) who resumed menses during the study showed an increase in BMD without normalization. CONCLUSION(S) These findings suggest that mechanisms other than hypoestrogenism may be involved with the osteopenia associated with exercise-induced amenorrhea.

Risk Factors for Increasing Multidrug Resistance among Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella Species

BACKGROUND The importance of infections due to extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) has been increasingly recognized in recent years. ESBL-EK infections are of clinical concern, because few antimicrobials are available as therapeutic options. Increased reliance on carbapenems has led to increasing carbapenem resistance. Efforts to maintain current therapeutic options for ESBL-EK infections are essential. METHODS We conducted a case-control study to identify risk factors for multidrug resistance (MDR) among ESBL-EK. All patients at our institution who had an inpatient clinical culture result positive for an ESBL-EK during the period of 1 June 1997 through 31 December 2002 were eligible for inclusion. An MDR ESBL-EK was defined as ESBL-EK demonstrating resistance to trimethoprim-sulfamethoxazole, aminoglycosides, and quinolones. All available ESBL-EK isolates were characterized by pulsed-field gel electrophoresis (PFGE). RESULTS Of 361 total ESBL-EK isolates, 68 (18.8%) were MDR. During the study period, the prevalence of MDR among ESBL-EK isolates increased from 12.5% to 26.9%. The only independent risk factor for MDR ESBL-EK was the infecting organism (i.e., Klebsiella pneumoniae; adjusted odds ratio, 11.7; 95% confidence interval, 4.77-28.51; P < .001). Prior antibiotic use was not independently associated with MDR ESBL-EK. PFGE patterns from K. pneumoniae isolates indicated close genetic relatedness among a substantial proportion of isolates. CONCLUSIONS The emergence of MDR among ESBL-EK has important implications for the future ability to treat these infections. The strong association between the species of infecting organism and MDR suggests that the epidemiology in K. pneumoniae may be unique. PFGE results suggest that horizontal spread is important in the emergence of MDR ESBL-EK.

Limiting the Emergence of Extended‐Spectrum β‐Lactamase–Producing Enterobacteriaceae: Influence of Patient Population Characteristics on the Response to Antimicrobial Formulary Interventions

BACKGROUND Effective methods to control the emergence of extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) remain unclear. Variations in the patient populations at different hospitals may influence the effect of antimicrobial formulary interventions. METHODS To examine variations across hospitals in the response to antimicrobial interventions (ie, restriction of ceftazidime and ceftriaxone) designed to curb the spread of ESBL-EK, we conducted a 5-year quasi-experimental study. This study was conducted at 2 hospitals within the same health system: Hospital A is a 625-bed academic medical center, and Hospital B is a 344-bed urban community hospital. All adult patients with a healthcare-acquired clinical culture of ESBL-EK from July 1, 1997 through December 31, 2002 were included. RESULTS After the interventions, the use of ceftriaxone decreased by 86% at Hospital A and by 95% at Hospital B, whereas the use of ceftazidime decreased by 95% at Hospital A and by 97% at Hospital B. The prevalence of ESBL-EK at Hospital A decreased by 45% (P < .001), compared with a 22% decrease at Hospital B (P = .36). The following variables were significantly more common among ESBL-EK-infected patients at Hospital B: residence in a long-term care facility (adjusted odds ratio, 3.77 [95% confidence interval, 1.70-8.37]), advanced age (adjusted odds ratio, 1.04 [95% confidence interval, 1.01-1.06]), and presence of a decubitus ulcer (adjusted odds ratio, 4.13 [95% confidence interval, 1.97-8.65]). CONCLUSIONS The effect of antimicrobial formulary interventions intended to curb emergence of ESBL-EK may differ substantially across institutions, perhaps as a result of differences in patient populations. Variability in the epidemiological profiles of ESBL-EK isolates at different hospitals must be considered when designing interventions to respond to these pathogens.

Mobile HIV Screening in Cape Town, South Africa: Clinical Impact, Cost and Cost-Effectiveness

Background Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa. Methods and Findings We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/µL, females 516/µL), CD4 count-dependent linkage to care rates (males 31%–58%, females 49%–58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs,

Ertapenem-Resistant Enterobacteriaceae: Risk Factors for Acquisition and Outcomes

29.30 per negative result and

Impact of different methods for describing the extent of prior antibiotic exposure on the association between antibiotic use and antibiotic-resistant infection.

31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be “very cost-effective” when the ICER was less than South Africas annual per capita Gross Domestic Product (GDP) (

HIV, tuberculosis, and noncommunicable diseases: what is known about the costs, effects, and cost-effectiveness of integrated care?

8,200 in 2012). We projected that, with medical facility-based testing, the discounted (undiscounted) HIV-infected population life expectancy was 132.2 (197.7) months; this increased to 140.7 (211.7) months with the addition of the mobile unit. The ICER for the mobile unit was

Lung Cancer Mortality Associated With Smoking and Smoking Cessation Among People Living With HIV in the United States

2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities. Conclusion The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority.

The Anticipated Clinical and Economic Effects of 90–90–90 in South Africa

BACKGROUND AND OBJECTIVE Carbapenem resistance among Enterobacteriaceae is of concern because of increasing prevalence and limited therapeutic options. Limited research has been focused on understanding ertapenem resistance as a more sensitive marker for resistance to other carbapenems. We sought to determine risk factors for acquisition of ertapenem-resistant, meropenem-susceptible, or intermediate Enterobacteriaceae and to assess associated patient outcomes. DESIGN Retrospective case-control study among adult hospitalized inpatients. SETTING A 902-bed quaternary care urban hospital. RESULTS Sixty-two cases of ertapenem-resistant Enterobacteriaceae were identified from March 14, 2006, through October 31, 2007, and 62 unmatched control patients were randomly selected from other inpatients with cultures positive for ertapenem-susceptible Enterobacteriaceae. Thirty-seven (60%) of case patient isolates were Enterobacter cloacae, 20 (32%) were Klebsiella pneumoniae, and 5 (8%) were other species of Enterobacteriaceae. Risk factors for ertapenem-resistant Enterobacteriaceae infection included intensive care unit stay (odds ratio [OR], 4.6 [95% confidence interval {CI}, 2.0-10.3]), vancomycin-resistant Enterococcus colonization (OR, 7.1 [95% CI, 2.4-21.4]), prior central venous catheter use (OR, 10.0 [95% CI, 3.0-33.1]), prior receipt of mechanical ventilation (OR, 5.8 [95% CI, 2.1-16.2]), exposure to any antibiotic during the 30 days prior to a positive culture result (OR, 18.5 [95% CI, 4.9-69.9]), use of a β-lactam during the 30 days prior to a positive culture result (OR, 6.9 [95% CI, 3.0-16.0], and use of a carbapenem during the 30 days prior to a positive culture result (OR, 18.2 [95% CI, 2.6-130.0]). For the 62 case patients, 30-day outcomes from the time of positive culture result were 24 discharges (39%), 10 deaths (16%), and 28 continued hospitalizations (44%). The final end point of the hospitalization was discharge for 44 patients (71%) and death for 18 patients (29%). CONCLUSIONS Ertapenem-resistant Enterobacteriaceae are important nosocomial pathogens. Multiple mechanisms of resistance may be in operation. Additional study of ertapenem resistance is needed.