Early (years) reactions: comparative analysis of early childhood policies and programs during the first wave of the COVID-19 pandemic.

BACKGROUND: During the first wave of COVID-19 there was little evidence to guide appropriate child and family programs and policy supports. METHODS: We compared policies and programs implemented to support early child health and well-being during the first wave of COVID-19 in Australia, Canada, the Netherlands, Singapore, the UK, and the USA. Program and policy themes were focused on prenatal care, well-baby visits and immunization schedules, financial supports, domestic violence and housing, childcare supports, child protective services, and food security. RESULTS: Significant heterogeneity in implementation of OECD-recommended policy responses was found with all of the included countries implementing some of these policies, but no country implementing supports in all of the potential areas. CONCLUSIONS: This analysis gives insight into initial government reactions to support children and families, and opportunities for governments to implement further supportive programs and policies during the current pandemic and future emergencies.

Community Distribution of Naloxone: A Systematic Review of Economic Evaluations.

BACKGROUND: As a core component of harm-reduction strategies to address the opioid crisis, several countries have instituted publicly funded programs to distribute naloxone for lay administration in the community. The effectiveness in reducing mortality from opioid overdose has been demonstrated in multiple systematic reviews. However, the economic impact of community naloxone distribution programs is not fully understood. OBJECTIVES: Our objective was to conduct a review of economic evaluations of community distribution of naloxone, assessing for quality and applicability to diverse contexts and settings. DATA SOURCES: The search strategy was performed on MEDLINE, Embase, and EconLit databases. STUDY ELIGIBILITY CRITERIA AND INTERVENTIONS: Search criteria were developed based on two themes: (1) papers involving naloxone or narcan and (2) any form of economic evaluation. A focused search of the grey literature was also conducted. Studies exploring the intervention of community distribution of naloxone were selected. STUDY APPRAISAL AND SYNTHESIS METHODS: Data extraction was done using the British Medical Journal guidelines for economic submissions, assigning quality levels based on the impact of the missing or unclear components on the strength of the conclusions. RESULTS: A total of nine articles matched our inclusion criteria: one cost-effectiveness analysis, eight cost-utility analyses, and one cost-benefit analysis. Overall, the quality of the studies was good (six of high quality, two of moderate quality, and one of low quality). All studies concluded that community distribution of naloxone was cost effective, with an incremental cost-utility ratio range of $US111-58,738 (year 2020 values) per quality-adjusted life-year gained. LIMITATIONS: Our search strategy was developed iteratively, rather than following an a priori design. Additionally, our search was limited to English terms. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Based on this review, community distribution of naloxone is a worthwhile investment and should be considered by other countries dealing with the opioid epidemic.

GDNF requires HIF-1α and RET activation for suppression of programmed cell death of enteric neurons by metabolic challenge.

Intestinal inflammation challenges both function and structure of the enteric nervous system (ENS). In the animal model of TNBS-induced colitis, an influx of immune cells causes early neuron death in the neuromuscular layers, followed by axonal outgrowth from surviving neurons associated with upregulation of the neurotrophin GDNF (glial cell line-derived neurotrophic factor). Inflammation could involve ischemia and metabolic inhibition leading to neuronal damage, which might be countered by a protective action of GDNF. This was examined in a primary co-culture model of rat myenteric neurons and smooth muscle, where metabolic challenge was caused by dinitrophenol (DNP), O-methyl glucose (OMG) or hypoxia. These caused the specific loss of 50% of neurons by 24 h that was blocked by GDNF both in vitro and in whole mounts. Neuroprotection was lost with RET inhibition by vandetanib or GSK3179106, which also caused neuron loss in untreated controls. Thus, both basal and upregulated GDNF levels signal via RET for neuronal survival. This includes a key role for upregulation of HIF-1α, which was detected in neurons in colitis, since the inhibitor chetomin blocked rescue by GDNF or ischemic pre-conditioning in vitro. In DNP-treated co-cultures, neuron death was not inhibited by zVAD, necrosulfonamide or GSK872, and cleaved caspase-3 or - 8 were undetectable. However, combinations of inhibitors or the RIP1kinase inhibitor Nec-1 prevented neuronal death, evidence for RIPK1-dependent necroptosis. Therefore, inflammation challenges enteric neurons via ischemia, while GDNF is neuroprotective, activating RET and HIF-1α to limit programmed cell death. This may support novel strategies to address recurrent inflammation in IBD.

The Role of Primary Care in a Pandemic: Reflections During the COVID-19 Pandemic in Canada.

As COVID-19 cases began to rise in Ontario, Canada, in March 2020, increasing surge capacity in hospitals and intensive care units became a large focus of preparations. As part of these preparations, primary care physicians were ready to be redeployed to the hospitals. However, due to the effective implementation of community-wide public health measures, the hospital system was not overwhelmed. As Ontario prepares now for a potential second wave of COVID-19, primary care physicians have an opportunity to consider the full breadth and depth of scope for primary care during a pandemic. From planning to surveillance to vaccination, primary care physicians are positioned to play a unique and vital role in a pandemic. Nevertheless, there are specific barriers that will need to be overcome.