Epidemiology and Management of invasive infections among people who Use drugs (EMU): protocol for a prospective, multicentre cohort study.

INTRODUCTION: People who inject drugs (PWID) are at risk of invasive infections such as bloodstream infections, endocarditis, osteomyelitis and septic arthritis. Such infections require prolonged antibiotic therapy, but there is limited evidence about the optimal care model to deliver to this population. The Epidemiology and Management of invasive infections among people who Use drugs (EMU) study aims to (1) describe the current burden, clinical spectrum, management and outcomes of invasive infections in PWID; (2) determine the impact of currently available models of care on completion of planned antimicrobials for PWID admitted to hospital with invasive infections and (3) determine postdischarge outcomes of PWID admitted with invasive infections at 30 and 90 days. METHODS AND ANALYSIS: EMU is a prospective multicentre cohort study of Australian public hospitals who provide care to PWIDs with invasive infections. All patients who have injected drugs in the previous six months and are admitted to a participating site for management of an invasive infection are eligible. EMU has two components: (1) EMU-Audit will collect information from medical records, including demographics, clinical presentation, management and outcomes; (2) EMU-Cohort will augment this with interviews at baseline, 30 and 90 days post-discharge, and data linkage examining readmission rates and mortality. The primary exposure is antimicrobial treatment modality, categorised as inpatient intravenous antimicrobials, outpatient antimicrobial therapy, early oral antibiotics or lipoglycopeptide. The primary outcome is confirmed completion of planned antimicrobials. We aim to recruit 146 participants over a 2-year period. ETHICS AND DISSEMINATION: EMU has been approved by the Alfred Hospital Human Research Ethics Committee (Project number 78815.) EMU-Audit will collect non-identifiable data with a waiver of consent. EMU-Cohort will collect identifiable data with informed consent. Findings will be presented at scientific conferences and disseminated by peer-review publications. TRIAL REGISTRATION NUMBER: ACTRN12622001173785; Pre-results.

Impact of Food Rations and Supplements on Micronutrient Status by Trimester of Pregnancy: Cross-Sectional Studies in the Maela Refugee Camp in Thailand.

Micronutrient fortified flour (MFF), supplementary food rations and micronutrient (MN) supplements may prevent deficiencies among pregnant women. Objectives of cross-sectional surveys in 2004 (n = 533) and 2006 (n = 515) were to assess the impact of new food rations (flour, oil) and supplements on MN status by trimester of pregnancy in the Maela refugee camp. Hemoglobin, iron status, zinc, retinol, ß-carotene and tryptophan decreased, while α-/γ-tocopherol and 5-methyltetrahydrofolate (5-MTHF) increased from first to third trimester. In 2006, mean zinc and α-tocopherol for each trimester was significantly higher than in 2004. The weeks of supplemented thiamine and folic acid were positively correlated with thiamine diphosphate (TDP) and 5-MTHF, but not for ferrous sulfate as iron deficiency was observed in 38.5% of third-trimester women. Frequent consumption of fish paste and owning a garden or animal were associated with significantly higher iron status, retinol, ß-carotene, and 5-MTHF. In conclusion, MFF and supplementary oil were most likely to explain improved zinc and α-tocopherol status, while thiamine and folate supplements ensured high TDP and 5-MTHF in late pregnancy. MN supplements, MN-rich staple food, small gardens, and programs to improve iron compliance are promising strategies to prevent MN deficiencies during pregnancy in vulnerable populations.

The practice and clinical implications of tablet splitting in international health.

OBJECTIVE: Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed. METHODS: We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded. RESULTS: Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets. CONCLUSION: These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended.

Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis.

BACKGROUND: Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. METHODS: We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage. RESULTS: If present on admission, shock, oligo-anuria, hypo- or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm's positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI) 97.8-99.9) and for survival to discharge 96.9% (95% CI 94.3-98.5). In the 712 patients receiving artesunate, the algorithm's positive predictive value for survival to 48 hours was 100% (95% CI 97.3-100) and to discharge was 98.5% (95% CI 94.8-99.8). CONCLUSIONS: Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.

A prospective assessment of the accuracy of commercial IgM ELISAs in diagnosis of Japanese encephalitis virus infections in patients with suspected central nervous system infections in Laos.

Japanese encephalitis virus (JEV) is a major cause of encephalitis in Asia. We estimated the diagnostic accuracy of two anti-JEV immunoglobulin M (IgM) enzyme-linked immunosorbent assays (ELISAs) (Panbio and XCyton JEVCheX) compared with a reference standard (AFRIMS JEV MAC ELISA) in a prospective study of the causes of central nervous system infections in Laos. Cerebrospinal fluid (CSF; 515 patients) and serum samples (182 patients) from those admitted to Mahosot Hospital, Vientiane, were tested. The CSF from 14.5% of acute encephalitis syndrome (AES) patients and 10.1% from those with AES and meningitis were positive for anti-JEV IgM in the reference ELISA. The sensitivities for CSF were 65.4% (95% confidence interval [CI] = 51-78) (Xcyton), 69.2% (95% CI = 55-81) (Panbio), however 96.2% (95% CI = 87-100) with Panbio Ravi criteria. Specificities were 89-100%. For admission sera from AES patients, sensitivities and specificities of the Panbio ELISA were 85.7% (95% CI = 42-100%) and 92.9% (95% CI = 83-98%), respectively.