Assessing the Impact of Salt Reduction Initiatives on the Chronic Disease Burden of Singapore

Globally, many countries are facing an increasing burden of chronic disease due to ageing populations, of which cardiovascular disease forms a large proportion. Excess dietary sodium contributes to cardiovascular disease risk and requires intervention at a population level. This study aimed to quantify the impact of several salt reduction initiatives on population health over a 30-year horizon using GeoDEMOS, a population model from Singapore. Four interventions were modelled in four demographic groups in 2020 for a total of 16 intervention scenarios. The effect of 0.5, 2.0, and 4.0 g/day reductions in daily salt consumption, along with adherence to the World Health Organization guidelines of a maximum of 5.0 g of salt each day, was modelled in the entire population, including the overweight and obese, the elderly, and diabetics. In each scenario, the number of averted incident cases of acute myocardial infarction and stroke, along with the disability-adjusted life years up to 2050, was monitored. We found 4.0 g/day reductions in salt consumption were the most effective when implemented across the entire population, resulting in 24,000 averted incident cases of cardiovascular disease and 215,000 disability-adjusted life years over 30 years. This is a large figure when compared with the 29,200 projected annual incident cases of cardiovascular disease in 2050. When targeted at specific high-risk demographic groups, the largest effects were observed in the overweight and obese, with the same intervention yielding 10,500 averted incident cases of cardiovascular disease and 91,500 disability-adjusted life years. Quantifying the benefits of salt reduction initiatives revealed a significant impact when administered across the entire population or the overweight and obese. Health promotion efforts directed toward sustainably reducing salt consumption will help to lower the chronic disease burden on the healthcare system in years to come.     

Depression, illness perception and coping in rheumatoid arthritis

This study aimed to establish the relationship between depression, illness perception, coping strategies, and adverse childhood events in rheumatoid arthritis patients. Sixty-two out-patients with rheumatoid arthritis (RA) completed the Hospital Anxiety and Depression Scale, Illness Perception Questionnaire, London Coping with Rheumatoid Arthritis Questionnaire, and Childhood Development Questionnaire, and underwent a clinical assessment of their physical state. Depressed patients were more disabled than the nondepressed, had a more negative view of their illness, and used more negative coping strategies. There was no association between depression and childhood adversity. Once disability was controlled for, there continued to be a significant correlation between depression and: (i) viewing the consequences of the illness negatively (Spearman's correlation coefficient [r]=0.37, p=0.003); and (ii) the perceived ability to control the illness (r= -0.26, p=0.04). The relationship between depression and negative coping strategies became insignificant. This study indicates the close relationship between depression and a negative view of the illness.     

Challenges of ethical research in resource-poor settings.

The disparity in resources between economically developed and developing countries presents ethical concerns when commercial sponsors of studies and investigators propose to conduct them with subjects in developing countries. Vulnerable people may be recruited into studies of little health benefit to themselves or their communities and, under undue inducements, may accept disproportionate risks. Reproductive health studies may present women with undue risks. Guidelines have been developed to protect exploitable populations in resource-poor settings, although guarding their right to make informed and voluntary choices poses special challenges. Guidelines pay special attention to pregnant women as research subjects, and may approve and even require their enrollment in studies of products not known to be harmful. Placebo-controlled studies are addressed in contexts where no recognized treatments are routinely accessible. The structure and functions of research ethics review committees present difficult challenges, but they may be mitigated by enlightened international collaboration.     

Past and future of biliary atresia

BACKGROUND: With the advent of liver transplantation the outcome of children with biliary atresia (BA) has improved. Is Kasai hepatic portoenterostomy (KHPE) still a valuable option for the treatment of these patients? METHODS: From 1974 to 1998, 77 patients with biliary atresia have been treated at our institution: 50 girls and 27 boys. RESULTS: Seventy-four patients had a KHPE, and 3 patients had no KHPE because of delay in diagnosis. A total of 65 of 74 patients (88%) had undergone KHPE type I, 4 patients (5.4%) KHPE type II, 3 patients (4%) had a Suruga modification, and 2 patients (2.6%) had a portocholecystostomy. Among the 74 patients, 11 were lost to follow-up and their cases were considered failures. Seventeen of our patients are alive at long-term follow-up after KHPE. Among the 77 patients, 33 (43%) had an orthotopic liver transplantation (OLT). Successful KHPE patients underwent transplant at a mean age of 9 years, and KHPE failed at a mean age of 11 months. A total of 25 of 77 (32%) of patients are alive thanks to OLT. In the cohort, the overall survival rate for the KHPE plus OLT is 42 of 77 (55%). Mortality and morbidity rates were more frequent among the younger patients who had early OLT after KHPE failure. In our series, overall survival rate was improved when the patient had a successful KHPE (P < .001). CONCLUSIONS: Kasai hepatic portoenterostomy (KHPE) continues to be a valuable procedure in the treatment of infants with biliary atresia (BA). Successful KHPE permits transplantation at an age at which mortality and morbidity are decreased leading to a better outcome.     

Alteration of macrophage anti-tumor activity and transferrin receptor expression by exposure to dimethylnitrosamine in vivo

Dimethylnitrosamine (DMN), a potent immunomodulatory agent, produces its effects on cell-mediated immune reactions through alterations in macrophage production and/or macrophage maturation/differentiation from bone marrow stem cells. Macrophages obtained by the in vitro culture of bone marrow from animals exposed to DMN in vivo (bone marrow-derived macrophages, BMDM) demonstrated enhanced cytotoxicity against L929 target cells. The enhanced cytotoxicity was also present in concanavalin A- and Corynebacterium parvum-elicited peritoneal exudate cells (PEC) obtained from DMN-exposed animals while thioglycollate-elicited PEC from DMN-exposed animals displayed no increase in their cytotoxic activity as compared to vehicle-exposed animals. However, treatment of thioglycollate-elicited PEC with interferon-gamma induced cytotoxic activity in PEC obtained from DMN-exposed animals but not in PEC obtained from control animals. BMDM obtained from DMN-exposed mice also demonstrated an alteration in the kinetics of the expression of the membrane-associated transferrin-binding receptor (mTFR), a marker of the activational status of macrophages. BMDM from animals exposed to DMN in vivo exhibited maximal expression of mTFR on day 7 of culture in vitro as compared to day 5 for BMDM from vehicle-exposed animals. C. parvum- and concanavalin A-elicited PEC from DMN-exposed animals showed dose-related decreases in their expression of mTFR which were associated with their expected enhanced cytotoxicity. Likewise, thioglycollate-elicited PEC from DMN-exposed mice had dose-related decreases in mTFR expression and total transferrin-binding activity, suggesting a change in their state of activation. No alterations in mTFR expression were observed in splenic macrophages. BMDM cultured with T cell-derived lymphokines known to affect mTFR expression demonstrated enhanced expression of mTFR independent of changes in the cell cycle profiles. Furthermore, while lymphokines enhanced mTFR expression, there was no alteration in the kinetics of mTFR expression by BMDM obtained from DMN- or vehicle-exposed animals. These results support the hypothesis that DMN-induced alterations in macrophage hematopoietic differentiation/maturation are manifested in changes in macrophage function.     

Drop‐offs in the isoniazid preventive therapy cascade among children living with HIV in western Kenya, 2015–2019

IntroductionIsoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited.MethodsWe evaluated the IPT cascade among CLHIV aged <15 years and newly enrolled in HIV care in eight HIV clinics in western Kenya. Medical record data were abstracted from September 2015 through July 2019. We assessed the proportion of CLHIV completing TB symptom screening, IPT eligibility assessment, IPT initiation and completion. TB incidence rate was calculated stratified by IPT initiation and completion status. Risk factors for IPT non‐initiation and non‐completion were assessed using Poisson regression with generalized linear models.ResultsOverall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97–99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1–3) were ineligible due to active TB and 828 (98%; 95% CI 97–99) were eligible. Five hundred and fifty‐nine (68%; 95% CI 64–71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5–10.2). Overall, 434 (78%; 95% CI 74–81) IPT initiators completed. Attending high‐volume HIV clinics (aRR = 2.82; 95% CI 1.20–6.62) was independently associated with IPT non‐initiation. IPT non‐initiation had a trend of being higher among those enrolled in the period 2017–2019 versus 2015–2016 (aRR = 1.91; 0.98–3.73) and those who were HIV virally non‐suppressed (aRR = 1.90; 95% CI 0.98–3.71). Being enrolled in 2017–2019 versus 2015–2016 (aRR = 1.40; 1.01–1.96) was independently associated with IPT non‐completion. By 24 months after IPT screening, TB incidence was four‐fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08–17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82–23.56).ConclusionsDespite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop‐offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6‐month course to reduce TB in CLHIV.     

Prevalence of low bone mineral density in inpatients with traumatic brain injury receiving neurobehavioural rehabilitation: a postoperative,observational study

Background

Osteoporosis is characterised by low bone mineral density (BMD) leading to an increased risk of fracture. Patients who have sustained a significant traumatic brain injury may have an increased risk of secondary reduced BMD as a result of immobility and other factors.

Objectives

To describe BMD in a cohort of patients recovering from traumatic brain injury, and to discuss the implications of the findings for physiotherapy practice.

Design

Prospective, observational.

Setting

Specialist, residential unit providing care for individuals with brain injury, many with a history of severe challenging behaviour.

Participants

Current inpatients (n = 51, 80% male) with the capacity to provide consent, as judged by their responsible clinician. The median age was 41 years (range 20 to 60 years), and the median time since the brain injury was sustained was 22 years (range 4 to 54 years).

Methods

Participants’ BMD was measured at the radius and tibia using quantitative ultrasound. Various clinical and demographic details were collected.

Results

Participants had suboptimal BMD measurements that were generally low for their age and gender. Nine (18%) participants met the criteria for osteopenia measured at the radius, and 26 (51%) participants met criteria for osteoporosis or osteopenia measured at the tibia.

Conclusions

Some participants had reduced BMD, putting them at risk of fracture or of developing such risk in the future. This group is at particular risk because they frequently display challenging aggressive behaviours that may be met with responses including proportionate use of manual restraint. Physiotherapists should bear this increased risk in mind when devising exercise programmes assessing risk in neurobehavioural rehabilitation settings.     

Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania

Leishmania parasites cause a spectrum of clinical pathology in humans ranging from disfiguring cutaneous lesions to fatal visceral leishmaniasis. We have generated a reference genome for Leishmania mexicana and refined the reference genomes for Leishmania major, Leishmania infantum, and Leishmania braziliensis. This has allowed the identification of a remarkably low number of genes or paralog groups (2, 14, 19, and 67, respectively) unique to one species. These were found to be conserved in additional isolates of the same species. We have predicted allelic variation and find that in these isolates, L. major and L. infantum have a surprisingly low number of predicted heterozygous SNPs compared with L. braziliensis and L. mexicana. We used short read coverage to infer ploidy and gene copy numbers, identifying large copy number variations between species, with 200 tandem gene arrays in L. major and 132 in L. mexicana. Chromosome copy number also varied significantly between species, with nine supernumerary chromosomes in L. infantum, four in L. mexicana, two in L. braziliensis, and one in L. major. A significant bias against gene arrays on supernumerary chromosomes was shown to exist, indicating that duplication events occur more frequently on disomic chromosomes. Taken together, our data demonstrate that there is little variation in unique gene content across Leishmania species, but large-scale genetic heterogeneity can result through gene amplification on disomic chromosomes and variation in chromosome number. Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression in response to environmental conditions in the host, providing a genetic basis for disease tropism.     

Building physician capacity for transformational leadership—Revisited

In 2001, St. Joseph's Health Centre reported on its efforts to design and deliver a physician leadership program. The program was launched in Fall 2010 and has just completed its second cohort with a total of 29 physicians participating. The results and associated learning have been very encouraging.     

Facilitating emergent change in a healthcare setting

During my doctoral research, I identified new ways of thinking about complexity in organizations. This involved embracing the capacity of complex systems to find their own form of order and coherence, often referred to as self-organization, and then asking the question, “What can organizational leaders do to create the systems and structures that would facilitate emergent change?” Emergent change comes from within and through the active members of a system and not according to some external prompting or design. This results in the sort of change capacity that enables an organization to be agile and resilient through a high level of employee engagement. The question was answered by identifying and validating organizational-specific factors that facilitate emergent change.