Restriction of oxycodone in the emergency department (ROXY-ED): A randomised controlled trial.

Background: The prescription of opioids in emergency care has been associated with harm, including overdose and dependence. The aim of this trial was to assess restriction of access to oxycodone (ROXY), in combination with education and guideline modifications, versus education and guideline modifications alone (standard care) to reduce oxycodone administration in the Emergency Department (ED). Methods: An unblinded, active control, randomised controlled trial was conducted in an adult tertiary ED. Participants were patients aged 18-75 years who had analgesics administered in the ED. The primary intervention was ROXY, through removal of all oxycodone immediate release tablets from the ED imprest, with availability of a small supply after senior clinician approval. The intervention did not restrict prescription of discharge medications. The primary outcome measure was oxycodone administration rates. Secondary outcomes were administration rates of other analgesic medications, time to initial analgesics and oxycodone prescription on discharge. Results: There were 2258 patients eligible for analysis. Oxycodone was administered to 80 (6.1%) patients in the ROXY group and 221 (23.3%) patients in the standard care group (relative risk (RR) 0.26; 95% CI: 0.21 to 0.33; p < .001). Tapentadol was prescribed more frequently in the ROXY group (RR 2.17; 95% CI: 1.71-2.74), while there were no differences in prescription of other analgesic medications. On discharge, significantly fewer patients were prescribed oxycodone (RR 0.51; 95% CI: 0.39-0.66) and no differences were observed in prescription rates of other analgesic medications. There was no difference in time to first analgesic (HR 0.94; 95% CI: 0.86-1.02). Conclusions: Restricted access to oxycodone was superior to education and guideline modifications alone for reducing oxycodone use in the ED and reducing discharge prescriptions of oxycodone from the ED. The addition of simple restrictive interventions is recommended to enable rapid changes to clinician behaviour to reduce the potential harm associated with the prescribing of oxycodone in the ED.

Representation: raising awareness of opportunities and skill development with undergraduate dental students.

Representatives for dentists are required for many governing committees, local and national, that contribute to many aspects of the profession related to politics, the workplace, education, or community-building. Developing skills as a representative can begin as an undergraduate in student representation systems as part of UK university governance structures. At one UK dental institution, there was a plan to explore the learning and skill development of current student representatives, review the training, identify any areas where there were gaps or where they should be strengthened, and consider whether a new training programme could be developed. Training gaps in the representation process and preference for peer mentoring in training were identified as students acknowledged learning 'on the job' through observation of experienced peers. Current representation training also fell short of highlighting the relevance to their future dental profession. Staff and students co-designed a bespoke programme of training to help students develop their representation skills, as well as align them to the development of professional skills which were determined to be relevant for their future dental career.

Experience of Treating COVID-19 With Remdesivir and Convalescent Plasma in a Resource-Limited Setting: A Prospective, Observational Study.

BACKGROUND: Convalescent plasma therapy (CPT) and remdesivir (REM) have been approved for investigational use to treat coronavirus disease 2019 (COVID-19) in Nepal. METHODS: In this prospective, multicentered study, we evaluated the safety and outcomes of treatment with CPT and/or REM in 1315 hospitalized COVID-19 patients over 18 years in 31 hospitals across Nepal. REM was administered to patients with moderate, severe, or life-threatening infection. CPT was administered to patients with severe to life-threatening infections who were at high risk for progression or clinical worsening despite REM. Clinical findings and outcomes were recorded until discharge or death. RESULTS: Patients were classified as having moderate (24.2%), severe (64%), or life-threatening (11.7%) COVID-19 infection. The majority of CPT and CPT + REM recipients had severe to life-threatening infections (CPT 98.3%; CPT + REM 92.1%) and were admitted to the intensive care unit (ICU; CPT 91.8%; CPT + REM 94.6%) compared with those who received REM alone (73.3% and 57.5%, respectively). Of 1083 patients with reported outcomes, 78.4% were discharged and 21.6% died. The discharge rate was 84% for REM (n = 910), 39% for CPT (n = 59), and 54.4% for CPT + REM (n = 114) recipients. In a logistic model comparing death vs discharge and adjusted for age, gender, steroid use, and severity, the predicted margin for discharge was higher for recipients of remdesivir alone (0.82; 95% CI, 0.79-0.84) compared with CPT (0.58; 95% CI, 0.47-0.70) and CPT + REM (0.67; 95% CI, 0.60-0.74) recipients. Adverse events of remdesivir and CPT were reported in <5% of patients. CONCLUSIONS: This study demonstrates a safe rollout of CPT and REM in a resource-limited setting. Remdesivir recipients had less severe infection and better outcomes.ClinicalTrials.gov identifier. NCT04570982.

ECMO (extra corporeal membrane oxygenation) in major trauma: A 10 year single centre experience.

Aim To review the indications, complications and outcomes of extracorporeal membrane oxygenation (ECMO) in major trauma patients. Methods Single centre, retrospective, cohort study. Results Over a ten year period, from 13,420 major trauma patients, 11 were identified from our institutional trauma registry as having received ECMO. These patients were predominantly younger (mean 39 +/- 17 years), male (91%) and severely traumatised (median ISS 50, IQR 34 - 54). Veno-venous (VV) ECMO was used predominantly (n = 7, 64%), to treat hypoxic respiratory failure (mean PaO2/FiO2 ratio 69.7 +/- 38.6), secondary to traumatic lung injury. Veno-arterial (VA) ECMO was used less frequently, primarily to treat massive pulmonary embolism following trauma. Major bleeding complications occurred in four patients, however only one patient died from haemorrhage. Heparin free (2/11), delayed (3/11) or low dose heparin (2/11) therapy was frequently utilised. The median time from injury to ECMO initiation was 1 day (IQR 0.5 - 5.5) and median ECMO duration 9 days (IQR 6.5 - 10.5). ECMO was initiated <72 hours in 6 patients, with survival to discharge 67%, compared to 20% in those initiated >72 hours. Overall survival to discharge was 45%, and was higher with VV ECMO (64%), than other configurations (25%). Conclusion ECMO was rarely used in major trauma, the most common indication being severe hypoxaemic respiratory failure secondary to lung injury. In this severely injured cohort, overall survival was poor but better in VV compared to VA and better if initiated early (<72 hours), compared to late.

Health problems in travellers to Nepal visiting CIWEC clinic in Kathmandu - A GeoSentinel analysis.

BACKGROUND: Nepal has always been a popular international travel destination. There is limited published data, however, on the spectrum of illnesses acquired by travellers to Nepal. METHODS: GeoSentinel is a global data collection network of travel and tropical medicine providers that monitors travel-related morbidity. Records for ill travellers with at least one confirmed or probable diagnosis, were extracted from the GeoSentinel database for the CIWEC Clinic Kathmandu site from January 1, 2009 to December 31, 2017. RESULTS: A total of 24,271 records were included. The median age was 30 years (range: 0-91); 54% were female. The top 3 system-based diagnoses in travellers were: gastrointestinal (32%), pulmonary (16%), and dermatologic (9%). Altitude illness comprised 9% of all diagnoses. There were 278 vaccine-preventable diseases, most frequently influenza A (41%) and typhoid fever (19%; S. typhi 52 and S. paratyphi 62). Of 64 vector-borne illnesses, dengue was the most frequent (64%), followed by imported malaria (14%). There was a single traveller with Japanese encephalitis. Six deaths were reported. CONCLUSIONS: Travellers to Nepal face a wide spectrum of illnesses, particularly diarrhoea, respiratory disease, and altitude illness. Pre-travel consultations for travellers to Nepal should focus on prevention and treatment of diarrhoea and altitude illness, along with appropriate immunizations and travel advice.

Epidemiology and clinical features of emergency department patients with suspected and confirmed COVID-19: A multisite report from the COVID-19 Emergency Department Quality Improvement Project for July 2020 (COVED-3).

OBJECTIVE: The aim of the present study was to describe the epidemiology and clinical features of patients presenting to the ED with suspected and confirmed COVID-19. METHODS: The COVID-19 ED (COVED) Project is an ongoing prospective cohort study in Australian EDs. This analysis presents data from eight sites across Victoria and Tasmania for July 2020 (during Australia's 'second wave'). All adult patients who met criteria for 'suspected COVID-19' and underwent testing for SARS-CoV-2 in the ED were eligible for inclusion. Study outcomes included a positive SARS-CoV-2 test result and mechanical ventilation. RESULTS: In the period 1 July to 31 July 2020, there were 30 378 presentations to the participating EDs and 2917 (9.6%; 95% confidence interval 9.3-9.9) underwent testing for SARS-CoV-2. Of these, 50 (2%) patients returned a positive result. Among positive cases, two (4%) received mechanical ventilation during their hospital admission compared to 45 (2%) of the SARS-CoV-2 negative patients (odds ratio 1.7, 95% confidence interval 0.4-7.3; P = 0.47). Two (4%) SARS-CoV-2 positive patients died in hospital compared to 46 (2%) of the SARS-CoV-2 negative patients (odds ratio 1.7, 95% confidence interval 0.4-7.1; P = 0.49). Strong clinical predictors of a positive SARS-CoV-2 result included self-reported fever, non-smoking status, bilateral infiltrates on chest X-ray and absence of a leucocytosis on first ED blood tests (P < 0.05). CONCLUSION: In this prospective multi-site study from July 2020, a substantial proportion of ED patients required SARS-CoV-2 testing, isolation and enhanced infection prevention and control precautions. Presence of SARS-CoV-2 on nasopharyngeal swab was not associated with death or mechanical ventilation.

Hepatitis C (HCV) therapy for HCV mono-infected and HIV-HCV co-infected individuals living in Nepal.

BACKGROUND: Despite direct-acting antivirals (DAA), aims to "eradicate" viral hepatitis by 2030 remain unlikely. In Nepal, an expert consortium was established to treat HCV through Nepal earthquakes aftermath offering a model for HCV treatment expansion in a resource-poor setting. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, we established a network of hepatologists, laboratory experts, and community-based leaders at 6 Opioid Substitution Treatment (OST) sites from 4 cities in Nepal screening 838 patients for a treatment cohort of 600 individuals with HCV infection and past or current drug use. During phase 1, patients were treated with interferon-based regimens (n = 46). During phase 2, 135 patients with optimal predictors (HIV controlled, without cirrhosis, low baseline HCV viral load) were treated with DAA-based regimens. During phase 3, IFN-free DAA treatment was expanded, regardless of HCV disease severity, HIV viremia or drug use. Sustained virologic response (SVR) was assessed at 12 weeks. Median age was 37 years and 95.5% were males. HCV genotype was 3 (53.2%) or 1a (40.7%) and 32% had cirrhosis; 42.5% were HIV-HCV coinfected. The intention-to-treat (ITT) SVR rates in phase 2 and 3 were 97% and 81%, respectively. The overall per-protocol and ITT SVR rates were 97% and 85%, respectively. By multivariable analysis, treatment at the Kathmandu site was protective and substance use, treatment during phase 3 were associated with failure to achieve SVR. CONCLUSIONS/SIGNIFICANCE: Very high SVR rates may be achieved in a difficult-to-treat, low-income population whatever the patient's profile and disease severity. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal.

Epidemiology and clinical features of emergency department patients with suspected COVID-19: Results from the first month of the COVID-19 Emergency Department Quality Improvement Project (COVED-2).

OBJECTIVE: The aim of the present study was to describe the epidemiological and clinical features of ED patients with suspected and confirmed COVID-19. METHODS: The COVID-19 Emergency Department (COVED) Project is an ongoing prospective cohort study that includes all adult patients presenting to The Alfred Hospital ED who undergo testing for SARS-CoV-2. Current guidelines recommend testing for patients with fevers or chills, acute respiratory symptoms or a high-risk exposure history, as well as implementation of infection prevention and control precautions for all suspected and confirmed cases. Study outcomes include a positive SARS-CoV-2 test result and intensive respiratory support. RESULTS: In the period 1-30 April 2020, 702 of 3453 ED patients (20%; 95% CI 19-22) were tested, with a significant increase during the study period (incident rate ratio 1.019; 95% confidence interval 1.017-1.021, P < 0.001). The primary outcome of a positive SARS-CoV-2 test was recorded in 14 patients (2%; 95% confidence interval 1-3). Shortness of breath (77%), fatigue (100%), myalgia (67%) and diarrhoea (67%) were common among positive cases, while close contact (9%), fever (0%) and healthcare occupation (0%) were not. No positive cases required intensive respiratory support in the ED. CONCLUSIONS: The volume of ED patients with suspected COVID-19 is increasing. Low numbers of positive cases precluded development of accurate predictive tools, but the COVED Project is fulfilling an important role in monitoring the burden of infection prevention and control requirements on the ED. The increasing number of patients meeting isolation criteria has the potential to impact on patient flow and may lead to ED overcrowding.

Traveler's diarrhea in Nepal-changes in etiology and antimicrobial resistance.

BACKGROUND: We conducted a comprehensive investigation to update our knowledge of traveler's diarrhea (TD) etiology and antimicrobial resistance (AMR) in Nepal. METHODS: A case-control study of TD etiology was conducted at the CIWEC Clinic Travel Medicine Center in Kathmandu from 2012 to 2014. Stool samples were tested by microscopy, culture and molecular techniques for identification of bacterial, viral and parasitic enteric pathogens, and AMR. We analysed patient demographic data, pre-treatment information and clinical outcomes. RESULTS: We enrolled 433 TD cases and 209 non-diarrhea controls. At least one of enteric pathogens was identified among 82% of cases and 44% of controls (P < 0.001). Multiple pathogens were observed among 35% of cases and 10% of controls. The most common pathogens significantly identified among cases in comparison with controls were Campylobacter (20%), norovirus (17%), enterotoxigenic E. coli (ETEC) (12%), rotavirus (9%) and Shigella (8%) (P < 0.001). We noted Campylobacter, Shigella and ETEC resistance to azithromycin at 8, 39 and 22% and to ciprofloxacin at 97, 78 and 23%, respectively. CONCLUSION: Among travellers to Nepal with TD, viral pathogens were commonly found and norovirus was the second most common pathogen after campylobacter. We noted increased AMR to fluoroquinolones (FQs) and azithromycin (AZM). There is heightened concern for AZM treatment failures, though this continues to remain the drug of choice for TD treatment in our setting where FQs should not be used.

Rabies post-exposure prophylaxis started during or after travel: A GeoSentinel analysis.

BACKGROUND: Recent studies demonstrate that rabies post-exposure prophylaxis (RPEP) in international travelers is suboptimal, with only 5-20% of travelers receiving rabies immune globulin (RIG) in the country of exposure when indicated. We hypothesized that travelers may not be receiving RIG appropriately, and practices may vary between countries. We aim to describe the characteristics of travelers who received RIG and/or RPEP during travel. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center review of international travelers exposed to potentially rabid animals, collecting information on RPEP administration. Travelers who started RPEP before (Group A) and at (Group B) presentation to a GeoSentinel clinic during September 2014-July 2017 were included. We included 920 travelers who started RPEP. About two-thirds of Group A travelers with an indication for rabies immunoglobulin (RIG) did not receive it. Travelers exposed in Indonesia were less likely to receive RIG in the country of exposure (relative risk: 0.30; 95% confidence interval: 0.12-0.73; P = 0.01). Travelers exposed in Thailand [Relative risk (RR) 1.38, 95% Confidence Interval (95% CI): 1.0-1.8; P = 0.02], Sri Lanka (RR 3.99, 95% CI: 3.99-11.9; P = 0.013), and the Philippines (RR 19.95, 95% CI: 2.5-157.2; P = 0.01), were more likely to receive RIG in the country of exposure. CONCLUSIONS/SIGNIFICANCE: This analysis highlights gaps in early delivery of RIG to travelers and identifies specific countries where travelers may be more or less likely to receive RIG. More detailed country-level information helps inform risk education of international travelers regarding appropriate rabies prevention.

Prevalence and management of diabetes in residential aged care facilities in north-east Victoria, Australia.

BACKGROUND: Managing diabetes in residential aged care facilities (RACFs) presents challenges to general practitioners (GPs) as the incidence of the disease increases. OBJECTIVE: The objective of this article is to describe the prevalence and management of diabetes in RACFs in north-east Victoria. METHODS: The method used for this study was a cross-sectional audit of medical files. RESULTS: Ten RACFs were invited and agreed to participate, giving a sample of 593 residents. Diabetes prevalence was 18.2% (n = 108). Half of the residents with diabetes had received a glycated haemoglobin (HbA1c) test in the previous six months. Of these residents, half had an HbA1c result of 8%. The frequency of hypoglycaemic events was found to be 10%. Hyperglycaemic episodes (HbA1C >10%) occurred in 69% of residents with diabetes; 21% had hyperglycaemic episodes when defined by levels greater than those set by the resident's GP. Diabetes-related unscheduled hospitalisations was found to be 6.5%, while diabetes-related general practice visits was 23%. DISCUSSION: The prevalence of diabetes in the RACFs was higher than previously reported in rural Victoria. Practice variance from evidence-based guidelines may be contributing to unplanned hospitalisations and increased acute general practice visits.

Pulmonary Embolism Masquerading as High Altitude Pulmonary Edema at High Altitude.

Pandey, Prativa, Benu Lohani, and Holly Murphy. Pulmonary embolism masquerading as high altitude pulmonary edema at high altitude. High Alt Med Biol. 17:353-358, 2016.-Pulmonary embolism (PE) at high altitude is a rare entity that can masquerade as or occur in conjunction with high altitude pulmonary edema (HAPE) and can complicate the diagnosis and management. When HAPE cases do not improve rapidly with descent, other diagnoses, including PE, ought to be considered. From 2013 to 2015, we identified eight cases of PE among 303 patients with initial diagnosis of HAPE. Upon further evaluation, five had deep vein thrombosis (DVT). One woman had a contraceptive ring and seven patients had no known thrombotic risks. PE can coexist with or mimic HAPE and should be considered in patients presenting with shortness of breath from high altitude regardless of thrombotic risk.

Biomarkers of hypoxia, endothelial and circulatory dysfunction among climbers in Nepal with AMS and HAPE: a prospective case-control study.

BACKGROUND: The mechanisms underlying acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) are not fully understood. We hypothesized that regulators of endothelial function, circulatory homeostasis, hypoxia and cell stress contribute to the pathobiology of AMS and HAPE. METHODS: We conducted a prospective case-control study of climbers developing altitude illness who were evacuated to the CIWEC clinic in Kathmandu, compared to healthy acclimatized climbers. ELISA was used to measure plasma biomarkers of the above pathways. RESULTS: Of the 175 participants, there were 71 cases of HAPE, 54 cases of AMS and 50 acclimatized controls (ACs). Markers of endothelial function were associated with HAPE: circulating levels of endothelin-1 (ET-1) were significantly elevated and levels of sKDR (soluble kinase domain receptor) were significantly decreased in cases of HAPE compared to AC or AMS. ET-1 levels were associated with disease severity as indicated by oxygen saturation. Angiopoietin-like 4 (Angptl4) and resistin, a marker of cell stress, were associated with AMS and HAPE irrespective of severity. Corin and angiotensin converting enzyme, regulators of volume homeostasis, were significantly decreased in HAPE compared to AC. CONCLUSION: Our findings indicate that regulators of endothelial function, vascular tone and cell stress are altered in altitude illness and may mechanistically contribute to the pathobiology of HAPE.

Spinal and paraspinal fungal infections associated with contaminated methylprednisolone injections.

BACKGROUND: A nationwide outbreak of fungal infections was traced to injection of Exserohilum-contaminated methylprednisolone. We describe our experience with patients who developed spinal or paraspinal infection after injection of contaminated methylprednisolone. METHODS: Data were assembled from the Michigan Department of Community Health, electronic medical records, and magnetic resonance imaging (MRI) reports. RESULTS: Of 544 patients who received an epidural injection from a contaminated lot of methylprednisolone at a pain clinic in southeastern Michigan, 153 (28%) were diagnosed at our institution with probable or confirmed spinal or paraspinal fungal infection at the injection site. Forty-one patients had both meningitis and spinal or paraspinal infection, and 112 had only spinal or paraspinal infection. Magnetic resonance imaging abnormalities included abscess, phlegmon, arachnoiditis, and osteomyelitis. Surgical debridement in 116 patients revealed epidural phlegmon and epidural abscess most often. Among 26 patients with an abnormal MRI but with no increase or change in chronic pain, 19 (73%) had infection identified at surgery. Fungal infection was confirmed in 78 patients (51%) by finding hyphae in tissues, positive polymerase chain reaction, or culture. Initial therapy was voriconazole plus liposomal amphotericin B in 115 patients (75%) and voriconazole alone in 38 patients (25%). As of January 31, 2014, 20 patients remained on an azole agent. Five patients died of infection. CONCLUSIONS: We report on 153 patients who had spinal or paraspinal fungal infection at the site of epidural injection of contaminated methylprednisolone. One hundred sixteen (76%) underwent operative debridement in addition to treatment with antifungal agents.

Travel-associated illness in older adults (>60 y).

BACKGROUND: Older individuals represent a substantial proportion of international travelers. Because of physiological changes and the increased probability of underlying medical conditions, older travelers might be at higher risk for at least some travel-associated diseases. METHODS: With the aim of describing the epidemiology of travel-associated diseases in older adults, medical data were prospectively collected on ill international travelers presenting to GeoSentinel sites from 1997 to 2009. Seven thousand thirty-four patients aged 60 years and over were identified as older travelers and were compared to 56,042 patients aged 18-45 years, who were used as the young adult reference population. RESULTS: The proportionate morbidity of several etiological diagnoses was higher in older ill travelers compared to younger ill, including notably lower respiratory tract infections, high-altitude pulmonary edema, phlebitis and pulmonary embolism, arthropod bites, severe malaria, rickettsiosis, gastritis, peptic ulcers, esophagitis and gastroesophageal reflux disease, trauma and injuries, urinary tract infections, heart disease, and death. In contrast, acute diarrhea, upper respiratory tract infections, flu and flu-like illnesses, malaria, dengue, genital infections, sexually transmitted diseases, and schistosomiasis proportionate morbidities were lower among the older group. CONCLUSION: Older ill travelers are more likely to suffer from certain life-threatening diseases and would benefit from reinforcement of specific preventive measures including use of anti-thrombosis compression stockings and sufficient hydration and exercises during long-distance flights, hand hygiene, use of disposable handkerchiefs, consideration of face-masks in crowded conditions, influenza and pneumococcal vaccines, progressive acclimatization to altitude, consideration of acetazolamide, and use of repellents and mosquito nets. Antibiotics for the presumptive treatment of respiratory and urinary tract infections may be considered, as well as antacid medications. At-risk patients should be referred to a specialist for medical evaluation before departing, and optimal control of co-morbidities such as cardiovascular and chronic obstructive pulmonary diseases should be achieved, particularly for high-altitude travel.

Pathogens for travelers' diarrhea in Nepal and resistance patterns.

At the top of the world, Nepal leads the world in travelers' diarrhea. A review of the rates, pathogens and resistance patterns over 3 decades reveals a persistent problem of increasing alarm. A look at root causes provides insight into this oppressive, inconvenient offense to travelers to an otherwise mystical Himalayan paradise.

Rickettsia honei infection in human, Nepal, 2009.

We report a case of Rickettsia honei infection in a human in Nepal. The patient had severe illness and many clinical features typical of Flinders Island spotted fever. Diagnosis was confirmed by indirect immunofluorescent assay with serum and molecular biological techniques. Flinders Island spotted fever may be an endemic rickettsiosis in Nepal.

Travelers' diarrhea in Nepal: an update on the pathogens and antibiotic resistance.

BACKGROUND: Diarrhea is the most common illness among travelers and expatriates in Nepal. Published data on the etiology of travelers' diarrhea (TD) in Nepal are over 13 years old and no prior data exist on antibiotic susceptibility for currently used drugs. We investigated the etiology of diarrhea and antimicrobial susceptibility pattern of bacterial pathogens and compared the results to previous work from the same clinical setting. METHODS: A total of 381 cases and 176 controls were enrolled between March 2001 and 2003 in a case-control study. Enrollees were over age 18 years from high socioeconomic countries visiting or living in Nepal. Stool samples were assessed by microbiologic, molecular identification, and enzyme immunoassay (EIA) methods, and antimicrobial susceptibility was determined by disk diffusion. Risk factors were assessed by questionnaires. RESULTS: At least one enteropathogen was identified in 263 of 381 (69%) cases and 47 of 176 (27%) controls (p ≤ 0.001). Pathogens significantly detected among cases were Campylobacter (17%), enterotoxigenic Escherichia coli (ETEC) (15%), Shigella (13%), and Giardia (11%). Cyclospora was detected only in cases (8%) mainly during monsoon season. Although 71% of Campylobacter isolates were resistant to ciprofloxacin, 80% of bacterial isolates overall were sensitive to either ciprofloxacin or azithromycin while 20% were intermediately sensitive or resistant. No bacterial isolates were resistant to both drugs. CONCLUSIONS: The most common pathogens causing TD in Nepal were Campylobacter, ETEC, and Shigella. Because resistance to fluoroquinolone or azithromycin was similar, one of these drugs could be used as empiric therapy for TD with the other reserved for treatment failures.

Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and chloroquine in healthy volunteers.

OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug-resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. SETTING: Tulane-Louisiana State University-Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS: 126 healthy adults 21-45 years of age. INTERVENTIONS: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract-related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0-14.7 l/h versus 9.5-11.3 l/h; p < or = 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics.