Severe organophosphate poisoning with delayed cholinergic crisis, intermediate syndrome and organophosphate induced delayed polyneuropathy on succession

Organophosphate compounds are the organic derivatives of Phosphorous containing acids and their effect on neuromuscular junction and Autonomic Synapses is clinically important. After exposure these agents cause acute and sub acute manifestations depending on the type and severity of the agents like Acute Cholinergic Manifestations, Intermediate Syndrome with Nicotinic features and Delayed Central Nervous System Complications. The patient reported here had severe Organophosphate Poisoning with various rare complications on a succession. This is the first report of Organophosphates Poisoning complicated by Intermediate Syndrome and Organophosphate Induced Delayed Polyneuropathy in Ethiopia and it is reported to increase awareness of health care workers on these rare complications of a common problem.     

Client Characteristics and HIV Risk Associated with Repeat HIV Testing Among Women in Ethiopia

In Ethiopia, the number of HIV tests administered doubled from 2007 to 2008. However, very little is known about the number of clients testing repeatedly in one year, or their motivations for doing so. We examine repeat HIV testing among 2,027 Ethiopian women attending eight VCT facilities in 2008. Multivariate logistic regression was used to examine associations between repeat HIV testing and demographic, behavioral, and psychosocial characteristics, as well as HIV status. Nearly 40% of clients had tested previously for HIV. Women with high sexual risk are nearly four times more likely than those with no sexual risk to have tested previously, but HIV prevalence was lower among repeat testers (6.5%) than first-time testers (8.5%). Moderate perceived vulnerability, or feeling powerless to prevent HIV infection, is associated with a 50% increased likelihood of being a repeat tester. High perceived behavioral risk is associated with a 40% reduction in the likelihood a woman is testing for at least the second time. Costs associated with repeat testing should be balanced against identification of new HIV cases and prevention benefits.     

Educational Attainment and HIV Status among Ethiopian Voluntary Counseling and Testing Clients

We examined the association between HIV infection and educational attainment level among a population of 34,512 voluntary counseling and testing (VCT) clients in Ethiopia, using client data from the Family Guidance Association of Ethiopia (FGAE). Overall, more than 50 percent of the VCT clients report at least secondary level educational attainment, and HIV prevalence is 8.5 percent for men and 14.3 percent for women. HIV prevalence decreases significantly with each increase in education level for both men and women, and this association persists at secondary and higher education levels in the multivariate model. Male and female VCT clients with more than secondary level education are 58 percent and 66 percent (respectively) less likely to be HIV-positive than those with no education. HIV prevention and treatment interventions in Ethiopia should target less educated segments of the population including women, who have higher HIV prevalence and lower educational attainment than men.     

Phase II Trial of Adjuvant Oral Thalidomide Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Disease from Colorectal/Appendiceal Cancer

Purpose

This phase II single-institution trial of adjuvant thalidomide after cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with appendiceal and colorectal malignancies sought to detect an improvement in progression-free survival (PFS) from 7 to 12 months.

Methods

Eligible patients received CS, HIPEC, and baseline imaging, followed by pretreatment thalidomide counseling. All participants were then started on a 28-day regimen of thalidomide, 100 mg by mouth at bedtime, followed by 200 mg for 4 weeks, followed by 300 mg as the final maintenance dose, as tolerated.

Results

Twenty-seven eligible patients (median age 52 years; 52 % appendiceal/48 % colorectal) were enrolled on this trial and included in the analysis, and 26 were evaluable for response. Eighteen patients demonstrated stable disease on adjuvant thalidomide, while eight showed evidence of progression. Approximately 30 % of the patients withdrew due to toxicity. Grade 3/4 toxicities included neurological disorders (16 %), nausea (12 %), vomiting (8 %), and thromboembolism (8 %). Median overall survival (OS) and PFS were 43.0 and 9.3 months, respectively, and median follow-up was 40.4 months. Multivariate modeling showed significant improvements in PFS and OS for appendiceal patients and those with R0 or R1 resections. On an intent-to-treat analysis, the PFS of the study group was 9 months.

Conclusions

Based on these findings, thalidomide cannot be recommended as adjuvant therapy after CS and HIPEC for gastrointestinal malignancies. Further research is needed to identify active agents in this population.     

Imaging sensitive and drug-resistant bacterial infection with [11C]-trimethoprim

BACKGROUNDSeveral molecular imaging strategies can identify bacterial infections in humans. PET affords the potential for sensitive infection detection deep within the body. Among PET-based approaches, antibiotic-based radiotracers, which often target key bacterial-specific enzymes, have considerable promise. One question for antibiotic radiotracers is whether antimicrobial resistance (AMR) reduces specific accumulation within bacteria, diminishing the predictive value of the diagnostic test.METHODSUsing a PET radiotracer based on the antibiotic trimethoprim (TMP), [¹¹C]-TMP, we performed in vitro uptake studies in susceptible and drug-resistant bacterial strains and whole-genome sequencing (WGS) in selected strains to identify TMP resistance mechanisms. Next, we queried the NCBI database of annotated bacterial genomes for WT and resistant dihydrofolate reductase (DHFR) genes. Finally, we initiated a first-in-human protocol of [¹¹C]-TMP in patients infected with both TMP-sensitive and TMP-resistant organisms to demonstrate the clinical feasibility of the tool.RESULTSWe observed robust [¹¹C]-TMP uptake in our panel of TMP-sensitive and -resistant bacteria, noting relatively variable and decreased uptake in a few strains of P. aeruginosa and E. coli. WGS showed that the vast majority of clinically relevant bacteria harbor a WT copy of DHFR, targetable by [¹¹C]-TMP, and that despite the AMR, these strains should be “imageable.” Clinical imaging of patients with [¹¹C]-TMP demonstrated focal radiotracer uptake in areas of infectious lesions.CONCLUSIONThis work highlights an approach to imaging bacterial infection in patients, which could affect our understanding of bacterial pathogenesis as well as our ability to better diagnose infections and monitor response to therapy.TRIAL REGISTRATIONClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03424525","term_id":"NCT03424525"}}NCT03424525.FUNDINGInstitute for Translational Medicine and Therapeutics, Burroughs Wellcome Fund, NIH Office of the Director Early Independence Award (DP5-OD26386), and University of Pennsylvania NIH T32 Radiology Research Training Grant (5T32EB004311-12).     

Evidence of changes in sexual behaviours among male factory workers in Ethiopia

OBJECTIVE: To assess changes in sexual behaviours among male factory workers in Ethiopia. DESIGN: Open cohort studies in two factories near Addis Ababa. DATA AND METHODS: At intake and biannual follow-up visits, data were collected on sexual behaviours including casual sex, sex with commercial sex workers (CSW), condom use, and history of sexually transmitted diseases (STDs) as indicated by genital discharge and genital ulcer. Health education, HIV testing, and counselling were offered to all participants. RESULTS: Between February 1997 and December 1999, 1124 males were enrolled in the two cohort studies. At intake, the prevalence of casual sex in the past year, sex with CSWs, condom use with the last casual partner, history of genital discharge in the past 5 years, and history of genital ulcer in the past 5 years were 9.7, 43.4, 38.8 (Akaki site only), 10.6 and 2.1%, respectively. At the Wonji site, the intake prevalence of casual sex, sex with CSW, and history of genital discharge decreased significantly by calendar year between 1997 and 1999. At both sites combined, between the first and the fourth follow-up visits, there was a decline in the proportion of males reporting recent casual sex (from 17.5 to 3.5%, < 0.001), sex with CSWs (from 11.2 to 0.75%, < 0.001), and genital discharge (from 2.1 to 0.6%, = 0.004). CONCLUSION: There was a decline over time in risky sexual behaviours reported by cohort participants. Part of this decline occurred independently of cohort interventions.     

Model based estimates of long-term persistence of inactivated hepatitis A vaccine-induced antibodies in adults

Background

In this paper, we review the results of existing statistical models of the long-term persistence of hepatitis A vaccine-induced antibodies in light of recently available immunogenicity data from 2 clinical trials (up to 17 years of follow-up).

Methods

Healthy adult volunteers monitored annually for 17 years after the administration of the first vaccine dose in 2 double-blind, randomized clinical trials were included in this analysis. Vaccination in these studies was administered according to a 2-dose vaccination schedule: 0, 12 months in study A and 0, 6 months in study B (NCT00289757/NCT00291876). Antibodies were measured using an in-house ELISA during the first 11 years of follow-up; a commercially available ELISA was then used up to Year 17 of follow-up. Long-term antibody persistence from studies A and B was estimated using statistical models for longitudinal data. Data from studies A and B were modeled separately.

Results

A total of 173 participants in study A and 108 participants in study B were included in the analysis. A linear mixed model with 2 changepoints allowed all available results to be accounted for. Predictions based on this model indicated that 98% (95%CI: 94–100%) of participants in study A and 97% (95%CI: 94–100%) of participants in study B will remain seropositive 25 years after receiving the first vaccine dose. Other models using part of the data provided consistent results: ≥95% of the participants was projected to remain seropositive for ≥25 years.

Conclusion

This analysis, using previously used and newly selected model structures, was consistent with former estimates of seropositivity rates ≥95% for at least 25 years.     

Reverse translation of phase I biomarker findings links the activity of angiotensin-(1--7) to repression of hypoxia inducible factor-1alpha in vascular sarcomas

ABSTRACT: BACKGROUND: In a phase I study of angiotensin-(1--7) [Ang-(1--7)], clinical benefit was associated with reduction in plasma placental growth factor (PlGF) concentrations. The current study examines Ang-(1--7) induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro. METHODS: Plasma biomarkers were measured prior to Ang-(1--7) administration as well as 1, 2, 3, 4, and 6 hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA). PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1--7) treatment in these cells. RESULTS: Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P = .007). Treatment of EOMA cells with increasing doses of Ang-(1--7) led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1--7) treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P = .04) and hypoxia inducible factor 1alpha (HIF-1alpha) expression (P < .001). CONCLUSIONS: Ang-(1--7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1alpha and PlGF expression.