Validation of the RETRIEVE (REverse TRIage EVEnts) Criteria for Same Day Return of Non-ST Elevation Acute Coronary Syndrome Patients to Referring Non-PCI Centres.

BACKGROUND: There are continuing bed constraints in percutaneous coronary intervention centres (PCI) so efficient patient triage from referral hospitals is pivotal. To evaluate a strategy of PCI centre (PCIC) bed-sparing we examined return of patients to referral hospitals screened by the RETRIEVE (REverse TRIage EVEnts) criteria and validated its use as a tool for screening suitability for same day transfer of non-ST-elevation acute coronary syndrome (NSTEACS) patients post PCI to their referring non-PCI centre (NPCIC). METHODS: From May 2008 to May 2011, 433 NSTEACS patients were prospectively screened for suitability for same day transfer back to the referring hospital at the completion of PCI. Of these patients, 212 were excluded from same day transfer using the RETRIEVE criteria and 221 patients met the RETRIEVE criteria and were transferred back to their NPCIC. RESULTS: Over the study period, 218 patients (98.6%) had no major adverse events. The primary endpoint (death, arrhythmia, myocardial infarction, major bleeding event, cerebrovascular accident, major vascular site complication, or requirement for return to the PCIC) was seen in only three transferred patients (1.4%). CONCLUSIONS: The RETRIEVE criteria can be used successfully to identify NSTEACS patients suitable for transfer back to NPCIC following PCI. Same day transfer to a NPCIC using the RETRIEVE criteria was associated with very low rates of major complications or repeat transfer and appears to be as safe as routine overnight observation in a PCIC.

Health-care availability, preference, and distance for women in urban Bo, Sierra Leone.

OBJECTIVES: To examine the diversity of the health-care providers in urban Bo, Sierra Leone, identify the types of health-care facilities preferred by women for fevers, and analyze the road network distances from homes to preferred health-care providers. METHODS: A population-based random sampling method was used to recruit 2419 women from Bo. A geographic information system was used to measure the road distance from each woman's home to her preferred provider. RESULTS: Preferred health-care providers for acute febrile illnesses (commonly referred to as "malaria" in the study communities) were hospitals (62.3 %), clinics (12.6 %), and pharmacies (12.4 %). Participants lived a median distance of 0.6 km from the nearest provider, but on average each woman lived 2.2 km one-way from her preferred provider. Women living farther from the city center had preferred providers significantly farther from home than women living downtown. CONCLUSIONS: The diverse health-care marketplace in Bo allows women to select clinical facilities from across the city. Most women prefer a malaria care provider farther from home than they could comfortably walk when ill.

Prevalence of cleft lip and cleft palate in rural north-central guatemala.

OBJECTIVE: To estimate the number of new cases of cleft lip and cleft palate in the department (state) of Alta Verapaz, Guatemala, in 2012. DESIGN: Cross-sectional survey of midwives from communities identified through a two-stage cluster-sampling process. Midwives were asked how many babies they had delivered in the past year and how many of those newborns had various types of birth defects, as illustrated in pictures. SETTING: Indigenous Mayan communities in rural north-central Guatemala. PARTICIPANTS: Midwives (n = 129) who had delivered babies in the previous year. MAIN OUTCOME MEASURE: Reports of babies born with cleft lip and cleft palate. RESULTS: A 1-year prevalence rate of 18.9 per 10,000 for cleft lip and 4.7 per 10,000 for cleft palate was estimated for Alta Verapaz. None of the cases of cleft lip also had cleft palate. CONCLUSION: The indigenous communities in north-central Guatemala might have a relatively high cleft lip prevalence rate compared with the global average.

A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma.

PURPOSE: A Phase II study to screen for anti-melanoma activity of the heat shock protein 90 (HSP90) inhibitor, 17-AAG (17-allylamino-17-demethoxygeldanamycin) was performed. The primary endpoint was the rate of disease stabilisation in patients with progressive, metastatic melanoma treated with 17-AAG. Secondary endpoints were to determine: the toxicity of 17-AAG, the duration of response(s), median survival and further study the pharmacokinetics and pharmacodynamics of 17-AAG. PATIENTS AND METHODS: Patients with metastatic melanoma (progressive disease documented ≤6 months of entering study) were treated with weekly, intravenous 17-AAG. A Simon one sample two stage minimax design was used. A stable disease rate of ≥25% at 6 months was considered compatible with 17-AAG having activity. RESULTS: Fourteen patients (8 male: 6 female) were entered, eleven received 17-AAG (performance status 0 or 1). Median age was 60 (range 29-81) years. The majority (93%) received prior chemotherapy and had stage M1c disease (71%). Toxicity was rarely ≥ Grade 2 in severity and commonly included fatigue, headache and gastrointestinal disturbances. One of eleven patients treated with 17-AAG had stable disease for 6 months and median survival for all patients was 173 days. The study was closed prematurely prior to completion of the first stage of recruitment and limited planned pharmacokinetic and pharmacodynamic analyses. CONCLUSION: Some evidence of 17-AAG activity was observed although early study termination meant study endpoints were not reached. Stable disease rates can be incorporated into trials screening for anti-melanoma activity and further study of HSP90 inhibitors in melanoma should be considered.

A geographic analysis of access to health services in rural Guatemala.

This paper uses road network analysis to quantify access to health care services in Alta Verapaz, a rural district in Guatemala with a majority Mayan population. Population data from the 2002 Guatemalan census, the location of health care facilities from the Ministry of Public Health and Social Assistance, and road and trail locations from the National Geographic Institute were included in a geographic information system (GIS). We computed the shortest path from each populated place to the nearest health care facility and then estimated the approximate travel time to the health facility based on road surface type. Road network analysis found that approximately 38.1% of residents of Alta Verapaz live within one hour of a hospital and 76.8% live within one hour of a basic care facility. In comparison, a circular buffer method found that 27.5% had access to a hospital and 94.5% had access to a primary care facility. Poverty was correlated with reduced access to care. The use of models that adjust for road types and allow for accurate estimation of travel times are helpful tools to identifying populations with limited access to health care services.

A phase I trial of epstein-barr virus gp350 vaccine for children with chronic kidney disease awaiting transplantation.

BACKGROUND.: Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative disease after transplantation. METHODS.: A phase I trial recruited children with chronic kidney disease to two successive cohorts given three injections of 12.5 microg (n=6) and 25 microg (n=10) recombinant gp350/alhydrogel vaccine over 6 to 8 weeks. RESULTS.: One in each cohort acquired wild EBV before the week 28 evaluation. Both doses were similarly immunogenic, inducing an IgG response in all 13 evaluable patients. Neutralizing antibodies were detected in four recipients (1/4 in the 12.5 microg and 3/9 in the 25 microg cohort). Median time from first vaccination to transplantation was 24 weeks. Immune responses declined rapidly and were unlikely to affect posttransplant events. DISCUSSION.: The vaccine was immunogenic but a prolonged vaccine schedule up to time of transplantation or improved adjuvants are required in future trials to reduce posttransplant EBV load and risk of lymphoproliferative disease.

A phase I trial of radioimmunotherapy with 131I-A5B7 anti-CEA antibody in combination with combretastatin-A4-phosphate in advanced gastrointestinal carcinomas.

PURPOSE: In preclinical models, radioimmunotherapy with (131)I-A5B7 anti-carcinoembryonic antigen (CEA) antibody ((131)I-A5B7) combined with the vascular disruptive agent combretastatin-A4-phosphate (CA4P) produced cures unlike either agent alone. We conducted a phase I trial determining the dose-limiting toxicity (DLT), maximum tolerated dose, efficacy, and mechanism of this combination in patients with gastrointestinal adenocarcinomas. EXPERIMENTAL DESIGN: Patients had CEA of 10 to 1,000 microg/L, QTc < or =450 ms, no cardiac arrhythmia/ischaemia, and adequate hematology/biochemistry. Tumor was suitable for blood flow analysis by dynamic contrast enhanced-magnetic resonance imaging (MRI). The starting dose was 1,800 MBq/m(2) of (131)I-A5B7 on day 1 and 45 mg/m(2) CA4P given 48 and 72 hours post-(131)I-A5B7, then weekly for up to seven weeks. RESULTS: Twelve patients were treated, with mean age of 63 years (range, 32-77). Two of six patients at the first dose level had DLTs (grade 4 neutropenia). The dose was reduced to 1,600 MBq/m(2), and CA4P escalated to 54 mg/m(2). Again, two of six patients had DLTs (neutropenia). Of ten assessable patients, three had stable disease and seven had progressive disease. Single-photon emission computed tomography confirmed tumor antibody uptake in all 10 patients. DCE-MRI confirmed falls in kinetic parameters (K(trans)/IAUGC(60)) in 9 of 12 patients. The change of both pharmacokinetic parameters reached a level expected to produce efficacy in one patient who had a minor response on computed tomography and a reduced serum tumor marker level. CONCLUSIONS: This is believed to be the first trial reporting the combination of radioimmunotherapy and vascular disruptive agent; each component was shown to function, and myelosuppression was dose-limiting. Optimal dose and timing of CA4P, and moderate improvements in the performance of radioimmunotherapy seem necessary for efficacy.