High-dose immunosuppression to prevent death after paraquat self-poisoning – a randomised controlled trial

Context: Intentional self-poisoning with the herbicide paraquat has a very high case-fatality and is a major problem in rural Asia and Pacific.

Objectives: We aimed to determine whether the addition of immunosuppression to supportive care offers benefit in resource poor Asian district hospitals.

Materials and methods: We performed a randomised placebo-controlled trial comparing immunosuppression (intravenous cyclophosphamide up to 1?g/day for two days and methylprednisolone 1?g/day for three days, and then oral dexamethasone 8?mg three-times-a-day for 14 days) with saline and placebo tablets, in addition to standard care, in patients with acute paraquat self-poisoning admitted to six Sri Lankan hospitals between 1st March 2007 and 15th November 2010. The primary outcome was in-hospital mortality.

Results: 299 patients were randomised to receive immunosuppression (147) or saline/placebo (152). There was no significant difference in in-hospital mortality rates between the groups (immunosuppression 78 [53%] vs. placebo 94 [62%] (Chi squared test 2.4, p?=?.12). There was no difference in mortality at three months between the immunosuppression (101/147 [69%]) and placebo groups (108/152 [71%]); (mortality reduction 2%, 95% CI: ?8 to +12%). A Cox model did not support benefit from high-dose immunosuppression but suggested potential benefit from the subsequent two weeks of dexamethasone.

Conclusions: We found no evidence that high dose immunosuppression improves survival in paraquat-poisoned patients. The continuing high mortality means further research on the use of dexamethasone and other potential treatments is urgently needed.     

AMEE Education Guide no. 28: the development and role of departments of medical education

A department of medical education is becoming an essential requirement for a medical school. This publication is intended for those wishing to establish or develop a medical education department. It may also prove useful to teachers in medicine by providing information on how such a department can support their activities. This will vary with the local context but the principles are generalizable. Medical education departments are established in response to increased public expectations relating to healthcare, societal trends towards increased accountability, educational developments, increased interest in what to teach and how to educate doctors and the need to train more doctors. The functions of a department of medical education include research, teaching, service provision and career development of the staff. The scope of its activities includes undergraduate and postgraduate education, continuing professional development and continuing medical education. These activities may be extended to other healthcare professions. Flexibility is the key to staffing a department of medical education. Various contractual arrangements, affiliations and support from non-affiliated personnel are needed to provide a multi-professional team with a range of expertise. The precise structure of the department will depend on the individual institution. The name of the department may suggest its position within the university structure. The director provides academic leadership for the department and his/her responsibilities include promotion of staff collaboration, fostering career development of the staff and establishing local, regional and international links. Financial support may come from external funding agencies, government or university sources. Some departments of medical education are financially self-supporting. The department should be closely integrated with the medical school. Support for the department from the dean is an essential factor for sustainability. Several case studies of medical education departments throughout the world are included as examples of the different roles and functions of a department of medical education.     

Survival pattern in patients with acute organophosphate poisoning receiving intensive care

BACKGROUND: Approximately 35% of patients acutely poisoned with organophosphates (OP) in developing countries like Sri Lanka require intensive care and mechanical ventilation. However, death rates remain high. OBJECTIVE: To study the outcomes and predictors of mortality in patients with acute OP poisoning requiring intensive therapy at a regional center in Sri Lanka over a period of 40 months. METHODS: Retrospective analysis of all intensive care records of patients with acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998 and July 2001. RESULTS: During the study period, 126 subjects were admitted to the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37 were incomplete and hence were excluded. All the remaining 71 patients (59 male) had required endotracheal intubation and mechanical ventilation for a period of four (median) days (range 1-27) in addition to gastric lavage and standard therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36 (28 male) had died. Life table analysis demonstrated a steep decline in the cumulative survival to 67% during the first three days. Systolic blood pressure of < 100 mmHg and FiO2 of >40% to maintain a SpO2 of >92% within the first 24 h were recognized as poor prognostic indicators among mechanically ventilated patients. CONCLUSION: Mortality following OP poisoning remains high despite adequate respiratory support, intensive care, and specific therapy with atropine and oximes. One-third of the subjects needing mechanical ventilation and reaching intensive care units die within the first 72 h of poisoning. Systolic blood pressure of less than 100 mmHg and the necessity of a FiO2>40% to maintain adequate oxygenation are predictors of poor outcome in patients mechanically ventilated in the ICU.     

Determinants of breastfeeding practices: an analysis of the Sri Lanka Demographic and Health Survey 2006-2007

Identification of factors that predict a woman's infant feeding choice is important for breastfeeding promotion programmes. We analysed a subsample of children under 2 years of age from the most recent Sri Lanka Demographic and Health Survey (SLDHS) to assess breastfeeding practices and factors associated with suboptimal practices. SLDHS 2006-2007 used a stratified two-stage cluster sample of ever-married women aged 15-49 years. Breastfeeding indicators were estimated for the last-born children (n = 2735). Selected indicators were examined against independent variables through cross-tabulations and multivariate analyses. Of the sample, 83.3% initiated breastfeeding within 1 h of birth. Continuation rates declined from 92.6% in first year to 83.5% in second year. Exclusive breastfeeding (EBF) rate under 6 months of age was 75.8%, with median duration being 4.8 months. Delayed initiation of breastfeeding was associated with low birthweight [odds ratio (OR) = 2.24] and caesarean delivery (OR = 3.30), but less likely among female infants (OR = 0.75), mothers from 'estate' sector (OR = 0.61) or richer wealth quintile (OR = 0.60). Non-EBF was associated with children from urban areas (OR = 1.72) and estate sector (OR = 4.48) and absence of post-natal visits by a public health midwife (OR = 1.89). A child was at risk for not currently breastfeeding if born in a private hospital (OR = 3.73), delivered by caesarean section (OR = 1.46) or lived in urban areas (OR = 2.80) or estate sector (OR = 3.23). Those living in estates (OR = 11.4) and not receiving post-natal home visits (OR = 2.62) were more likely to discontinue breastfeeding by 1 year. Breastfeeding indicators in Sri Lanka were higher compared with many countries and determined by socio-economic and health care system factors.     

Health changes in sri lanka: benefits of primary health care and public health

The Democratic Socialist Republic of Sri Lanka is an island in the Indian Ocean that has achieved a unique status in the world with health indicators that are comparable with those of developed countries. This is illustrated, among others, by the reduction in both child and maternal mortality in the country. This achievement is the result of a range of long-term interventions, including providing education and health care free of charge, training of health care workers, developing public health infrastructure in rural areas, and adopting steps to improve sanitation, nutrition, and immunization coverage.     

The impact of COVID‐19 on clinical outcomes among acute myocardial infarction patients undergoing early invasive treatment strategy

BackgroundThe implications of coronavirus disease 2019 (COVID‐19) infection on outcomes after invasive therapeutic strategies among patients presenting with acute myocardial infarction (AMI) are not well studied.HypothesisTo assess the outcomes of COVID‐19 patients presenting with AMI undergoing an early invasive treatment strategy.MethodsThis study was a cross‐sectional, retrospective analysis of the National COVID Cohort Collaborative database including all patients presenting with a recorded diagnosis of AMI (ST‐elevation myocardial infarction (MI) and non‐ST elevation MI). COVID‐19 positive patients with AMI were stratified into one of four groups: (1a) patients who had a coronary angiogram with percutaneous coronary intervention (PCI) within 3 days of their AMI; (1b) PCI within 3 days of AMI with coronary artery bypass graft (CABG) within 30 days; (2a) coronary angiogram without PCI and without CABG within 30 days; and (2b) coronary angiogram with CABG within 30 days. The main outcomes were respiratory failure, cardiogenic shock, prolonged length of stay, rehospitalization, and death.ResultsThere were 10 506 COVID‐19 positive patients with a diagnosis of AMI. COVID‐19 positive patients with PCI had 8.2 times higher odds of respiratory failure than COVID‐19 negative patients (p = .001). The odds of prolonged length of stay were 1.7 times higher in COVID‐19 patients who underwent PCI (p = .024) and 1.9 times higher in patients who underwent coronary angiogram followed by CABG (p = .001).ConclusionThese data demonstrate that COVID‐19 positive patients with AMI undergoing early invasive coronary angiography had worse outcomes than COVID‐19 negative patients.     

From the Cover: The emergence of lineage-specific chromosomal topologies from coordinate gene regulation

Although the importance of chromosome organization during mitosis is clear, it remains to be determined whether the nucleus assumes other functionally relevant chromosomal topologies. We have previously shown that homologous chromosomes have a tendency to associate during hematopoiesis according to their distribution of coregulated genes, suggesting cell-specific nuclear organization. Here, using the mathematical approaches of distance matrices and coupled oscillators, we model the dynamic relationship between gene expression and chromosomal associations during the differentiation of a multipotential hematopoietic progenitor. Our analysis reveals dramatic changes in total genomic order: Commitment of the progenitor results in an initial increase in entropy at both the level of gene coregulation and chromosomal organization, which we suggest represents a phase transition, followed by a progressive decline in entropy during differentiation. The stabilization of a highly ordered state in the differentiated cell types results in lineage-specific chromosomal topologies and is related to the emergence of coherence—or self-organization—between chromosomal associations and coordinate gene regulation. We discuss how these observations may be generally relevant to cell fate decisions encountered by progenitor/stem cells.