Sector wide approaches for health in small island states: lessons learned from the Solomon Islands

Sector Wide Approaches (SWAps) have increasingly been implemented in countries around the world as a mechanism for effective delivery of health sector funding from various sources. Despite the global focus on aid effectiveness, SWAps have been under-examined. In 2007, the Solomon Islands and development partners began discussing a health SWAp making the Solomon Islands one of the first fragile states globally to adopt a SWAp. This paper explores the establishment and implementation of a health SWAp in the Solomon Islands as a specific case study with lessons learned for the region as well as for aid architecture in fragile states more generally. Tensions between donors and the government impeded agreement and early implementation and country ownership of the SWAp idea was muted. Since mid-2009, however, the Solomon Islands SWAp has made strong progress with greater government ownership and with more focus on partnership and harmonisation rather than on funding mechanisms. The SWAp mechanism has been a challenge for the capacity-constrained Solomon Islands health sector and for development partners familiar with other aid modalities, but current momentum suggests that the SWAp will have a positive impact on adherence to agreed aid effectiveness principles.     

Sensitivity and responsiveness of the medical research council dyspnoea scale to the presence and treatment of adult laryngotracheal stenosis

Objectives: To assess the sensitivity and responsiveness of the Medical Research Council (MRC) scale, a psychophysical dyspnoea assessment instrument to the presence and treatment of adult laryngotracheal stenosis. Design: Prospective observational study. Settings: Tertiary/National referral airway reconstruction centre. Participants: Fourty tracheostomy‐free patients undergoing endoscopic airway examination/laryngotracheoplasty. Main outcome measures: Demographic and clinical information, obtained from patient records, lesion severity, which was recorded intraoperatively, standard spirometry, which was measured preoperatively, and the MRC dyspnoea scale, which was administered preoperatively and at the first outpatient visit 4–6 weeks later. Results: There were 16 males and 24 females. Mean age at presentation was 44 ± 14 years (± SD). Postintubation stenosis was the commonest aetiology (73%) followed by idiopathic subglottic stenosis and Wegener’s Granulomatosis. Six patients were examined post‐treatment and had minimal residual stenosis and the remaining patients had glottic stenosis (n = 11) or Myer–Cotton Grade I (n = 8), II (n = 7) or III (n = 8) tracheal stenoses. Pre‐treatment MRC dyspnoea scores and the degree of change in the MRC score following treatment strongly correlated with pre‐treatment stenosis severity (r = 0.75 and r = ?0.71 respectively; P < .001). Moreover statistically significant correlations existed between preoperative peak expiratory flow and forced expiratory volume in 1 s and preoperative MRC dyspnoea scores (r = ?0.34 and r = ?0.35 respectively; P < 0.05). Discussion: Exertional dyspnoea is the hallmark symptom of laryngotracheal stenosis and for many patients it is the primary cause of disability. These findings confirm that the MRC dyspnoea scale is an appropriate outcome instrument for assessing dyspnoea associated with this condition.     

Intersectin regulates epidermal growth factor receptor endocytosis, ubiquitylation, and signaling

Receptor tyrosine kinases (RTKs) are critical for normal cell growth, differentiation, and development, but they contribute to various pathological conditions when disrupted. Activation of RTKs stimulates a plethora of pathways, including the ubiquitylation and endocytosis of the receptor itself. Although endocytosis terminates RTK signaling, it has emerged as a requisite step in RTK activation of signaling pathways. We have discovered that the endocytic scaffolding protein intersectin (ITSN) cooperated with epidermal growth factor receptor (EGFR) in the regulation of cell growth and signaling. However, a biochemical link between ITSN and EGFR was not defined. In this study, we demonstrate that ITSN is a scaffold for the E3 ubiquitin ligase Cbl. ITSN forms a complex with Cbl in vivo mediated by the Src homology (SH) 3 domains binding to the Pro-rich COOH terminus of Cbl. This interaction stimulates the ubiquitylation and degradation of the activated EGFR. Furthermore, silencing ITSN by RNA interference attenuated EGFR internalization as well as activation of the extracellular signal-regulated kinasemitogen-activated protein kinase pathway, thereby demonstrating the importance of ITSN in EGFR function. Given the cooperativity between ITSN and additional RTKs, these results point to an important evolutionarily conserved, regulatory role for ITSN in RTK function that is necessary for both signaling from receptors as well as the ultimate termination of receptor signaling.     

Nitric oxide reversibly impairs axonal conduction in Guinea pig spinal cord

Increased expression of the inducible and neuronal isoforms of nitric oxide synthase (NOS), and elevated concentrations of nitric oxide (NO) metabolites, are present within the central nervous system (CNS) following neurotrauma and are implicated in the pathogenesis of the accompanying neurologic deficits. We tested the hypothesis that elevated extracellular concentrations of NO introduced by the donor Spermine NONOate, induce reversible axonal conduction deficits in neurons of the guinea pig spinal cord. The compound action potential (CAP) and compound membrane potential (CMP) of excised ventral cord white matter were recorded before, during, and after bathing the tissue (30 min) in varying concentrations (0.25-3.0 mM) of Spermine NONOate. The principal results were a rapid onset, dose-dependent, reduction in amplitude of the CAP (p < 0.05) accompanied by depolarization of the CMP during NO exposure. These effects were largely reversible on washout, at low concentration of the donor (0.5 mM), but were only partially reversed at higher concentrations. Changes in the electrophysiological properties were not evident when the donor had been a priori depleted of NO. The results extend previous reports that NO induces reversible axonal conduction deficits. They provide new evidence of dissociation of the effects of NO on CAP and CMP during washout, and after prolonged exposure to the donor. They add support to the emerging concept that immune-mediated axonal conduction failure contributes to reversible neurologic deficits following neurotrauma and aid in understanding clinical phenomena such as spinal shock and neurologic recovery.     

Surface area: a better predictor of disease severity than the height and volume of the barium column in patients with primary achalasia

OBJECTIVE: Subjective assessment of primary achalasia is not accurate. We aimed to study the utility of surface area of barium retention in the objective assessment of these patients. METHODS: Subjective and objective esophageal functions of 99 patients with primary achalasia were evaluated initially and 43 of them were reevaluated 1 month after balloon dilation. RESULTS: Before dilation: Ninety-nine patients were enrolled. Forty-one of them were male. The mean age was 37.5+/-15.3 years. The mean score, resting lower esophageal sphincter pressure, height, surface and volume of barium retention at 5 min were 8.03+/-3.1, 59.1+/-20 mmHg, 9.9+/-4.9 cm, and 23.6+/-13.9 cm and 53.2+/-47.7 cm, respectively. Surface area at 5 min had best correlation and predictive value for resting lower esophageal sphincter pressure. After dilation: Forty-three of 99 patients were reevaluated after balloon dilation. The mean age was 36.8+/-13.6 years. Seventeen of them were male. Mean score, resting lower esophageal sphincter pressure, height, surface area and volume of barium retention at 5 min dropped significantly after dilation. Surface area at 5 min had best correlation and predictive value for lower esophageal sphincter pressure. CONCLUSIONS: Surface area of barium retention at 5 min is an accurate objective tool to assess patients with primary achalasia. It is cheap and easy to perform; therefore, it could be used more frequently in postdilation follow-up.     

Influence of acute and sub-chronic nicotine pretreatment on morphine state-dependent learning

In the present study, the effects of acute and sub-chronic pretreatment of nicotine on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice. Pre-training administration of morphine (5mg/kg) decreased the learning of a one-trial passive avoidance task, which was reversed by pre-test administration of the same dose of morphine. Amnesia induced by pre-training morphine was also significantly reversed in nicotine (0.001, 0.01 and 0.1 mg/kg)-treated animals on the test day. Morphine induced amnesia was also reversed in animals which had previously received sub-chronic injections of nicotine, once daily for 3 days followed by 14 days of no drug treatment. The restoration of memory by pre-test morphine was also reduced in animals which had previously received once daily injections of atropine (0.25, 0.5 and 1 mg/kg, i.p.) for 3 days after 14 of being days drug free. In the animals, restoration of memory by sub-chronic nicotine administration, was also decreased by once daily administration of atropine (0.25, 0.5 and 1 mg/kg) 10 min prior to injection of nicotine (0.1 microg/kg/day, for 3 days) but not with SCH 23390; R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl (0.01, 0.05 and 0.1 mg/kg) or sulpiride (25, 50 and 100 mg/kg) during 3-days of treatment with nicotine. The results suggest that nicotine may induce sensitization which affects the impairment of memory formation via cholinergic but not dopaminergic systems.     

Using qualitative methods to inform the design of a decision aid for people with advanced cystic fibrosis: The InformedChoices CF patient decision aid

ObjectiveTo assess information needs of adults with Cystic Fibrosis and their families toward designing a patient decision aid about invasive mechanical ventilation (IMV) and lung transplant.MethodsFocus groups and in-depth interviews explored participants’ knowledge, prior clinical conversations, and decisions about IMV and lung transplant. Interviews and focus groups were recorded and transcribed for analysis.ResultsN = 24 participants were recruited. Themes identified were: prior communication with clinicians, decision-making process, and living with CF. Participants having prior conversations with CF clinicians regarding: lung transplant (N = 17/74%), and IMV (N = 3/13%). Most 15(65%) felt it was important to hear patients’ real-life experience, others (3/13%) relied on their CF doctors for information. Most people (16/70%) believed hearing prognosis was helpful, but 5(22%) found this information frightening. High degrees of social isolation and a desire for more interaction with other CF adults were found.ConclusionsQualitative methods helped identify areas important for decision making about IMV and LT for CF adults. Future directions include usability and feasibility testing of the decision aid.Practice implicationsBecause IMV is rarely discussed with CF adults, clinicians might approach this topic, as with transplant, as lung function begins to decline. CF-care teams should also foster CF patient-level information exchange.     

Prenatal and perinatal factors associated with developing multiple sclerosis later in life: A systematic review and meta-analysis

ObjectiveBoth genetic and environmental factors play roles in Multiple Sclerosis (MS) etiopathogenesis. The relationship between prenatal/perinatal factors/exposures and future MS occurrence in the offspring remains controversial. Here, we aimed to review the available evidence on prenatal/perinatal factors associated with later MS occurrence.MethodWe performed systematic search of PubMed, Web of Science, and Scopus from inception to October 2020. We included original observational studies conducted on human participants addressing the association between prenatal/perinatal factors and MS occurrence. Data were extracted according to the PRISMA guideline. The adjusted odds ratio (OR) with 95% confidence interval (CI) was considered as the desired effect size. The heterogeneity was evaluated by Cochran's Q and I² and the publication bias was assessed. We excluded gestational/neonatal vitamin D level, season of birth, and latitude because of recently published systematic reviews/meta-analyses on these subjects.ResultsOverall, 2306 records were identified in the primary search. After excluding irrelevant studies, we evaluated 34 studies with contributing data on 100 prenatal/perinatal factors associated with an increased or decreased risk of MS occurrence. In the meta-analyses, we found no statistically significant associations between later MS occurrence in offspring and prenatal smoking exposure (OR = 1.01, 95% CI = 0.77–1.34), mode of delivery (OR = 0.90, 95% CI = 0.52–1.56), birth order (OR = 0.85, 95% CI = 0.72–1.00), and maternal age (OR = 1.34, 95% CI = 0.88–2.04). Paternal age and parents' marital status at the time of childbirth, maternal preeclampsia/ toxemia, forceps use, birth weight, plurality, and preterm birth were the other most studied factors, and none reported to affect MS risk.ConclusionWe found that prenatal smoking exposure, mode of delivery, birth order, and maternal age do not affect risk of future MS development. Moreover, most of the other investigated factors were reported not to affect MS risk in the offspring.     

Health expenditure and catastrophic spending among older adults living with HIV

Introduction: The burden of HIV is increasing among adults aged over 50, who generally experience increased risk of cormorbid illnesses and poorer financial protection. We compared patterns of health utilisation and expenditure among HIV-positive and HIV-negative adults over 50. Methods: Data were drawn from the Study on global AGEing and adult health in South Africa with analysis focusing on individual and household-level data of 147 HIV-positive and 2725 HIV-negative respondents. Results: HIV-positive respondents reported lower utilisation of private health-care facilities (11.8%) than HIV-negative respondents (25.0%) (p?=?.03) and generally had more negative attitudes towards health system responsiveness than HIV-negative counterparts. Less than 10% of HIV-positive and HIV-negative respondents experienced catastrophic health expenditure (CHE). Women (OR 1.8; p?p?Conclusions: These findings suggest that although HIV-positive and HIV-negative older adults in South Africa are protected to some extent from CHE, inequalities still exist in access to and quality of care available at health-care services – which can inform South Africa’s development of a national health insurance scheme.