Increased Elastase and Matrix Metalloproteinase Levels in the Pulmonary Arteries of Infants With Congenital Diaphragmatic Hernia.

BACKGROUND: Pulmonary vascular disease (PVD) complicated with pulmonary hypertension (PH) is a leading cause of mortality in congenital diaphragmatic hernia (CDH). Unfortunately, CDH patients are often resistant to PH therapy. Using the nitrogen CDH rat model, we previously demonstrated that CDH-associated PVD involves an induction of elastase and matrix metalloproteinase (MMP) activities, increased osteopontin and epidermal growth factor (EGF) levels, and enhanced smooth muscle cell (SMC) proliferation. Here, we aimed to determine whether the levels of the key members of this proteinase-induced pathway are also elevated in the pulmonary arteries (PAs) of CDH patients. METHODS: Neutrophil elastase (NE), matrix metalloproteinase-2 (MMP-2), epidermal growth factor (EGF), tenascin-C, and osteopontin levels were assessed by immunohistochemistry in the PAs from the lungs of 11 CDH patients and 5 normal age-matched controls. Markers of proliferation (proliferating cell nuclear antigen (PCNA)) and apoptosis (cleaved (active) caspase-3) were also used. RESULTS: While expressed by both control and CDH lungs, the levels of NE, MMP-2, EGF, as well as tenascin-C and osteopontin were significantly increased in the PAs from CDH patients. The percentage of PCNA-positive PA SMCs were also enhanced, while those positive for caspase-3 were slightly decreased. CONCLUSIONS: These results suggest that increased elastase and MMPs, together with elevated tenascin-C and osteopontin levels in an EGF-rich environment may contribute to the PVD in CDH infants. The next step of this study is to expand our analysis to a larger cohort, and determine the potential of targeting this pathway for the treatment of CDH-associated PVD and PH. TYPE OF STUDY: Therapeutic. LEVEL OF EVIDENCE: LEVEL III.

"Apparently, you can only be treated once": A qualitative study exploring perceptions of hepatitis C and access to treatment among people who inject drugs visiting a needle and syringe program.

BACKGROUND: Access to hepatitis C care within harm reduction community organizations for people who inject drugs is crucial for achieving hepatitis C elimination. However, there is a lack of data on how perceptions of hepatitis C and treatment have changed among individuals visiting these organizations during the era of direct-acting antivirals (DAAs). This study aimed to explore the perceptions of hepatitis C and treatment access for (re)infection among individuals visiting a needle and syringe program in Canada. METHODS: Eighteen semi-structured interviews were conducted with individuals who recently injected drugs and visited a needle and syringe program. The interviews were guided by the Common-Sense Self-Regulation Model (CS-SRM) and aimed to explore cognitive and emotional representations of hepatitis C, perceptions of treatment, coping strategies and sources of information. Interviews were audio recorded, transcribed, and coded using thematic analysis. RESULTS: Most of the participants identified as male, were of white ethnicity and had a median age of 45. While most underscored the therapeutic advancements and the effectiveness of DAAs, they expressed confusion regarding the mechanisms of access to treatment, especially in cases of reinfection. Perceptions of the controllability of hepatitis C were significantly influenced by the stigmatizing discourse surrounding treatment access, cost, and public coverage. This influence extended to their intentions for seeking treatment. Participants emphasized the social consequences of hepatitis C, including stigma. Emotional representations of hepatitis C evolved along the care cascade, encompassing initial shock at diagnosis and later fear of reinfection following successful treatment. CONCLUSION: Nearly a decade after the advent of DAAs, misinformation about treatment access persists. Findings underscore a nexus of internalized and institutionalized stigma associated with hepatitis C, drug use, and the challenges of cost and access to treatment, pointing to a clear need for education and service delivery optimisation in harm reduction community organizations.

A comprehensive review of prioritised interventions to improve the health and wellbeing of persons with lived experience of homelessness.

Background: Homelessness has emerged as a public health priority, with growing numbers of vulnerable populations despite advances in social welfare. In February 2020, the United Nations passed a historic resolution, identifying the need to adopt social-protection systems and ensure access to safe and affordable housing for all. The establishment of housing stability is a critical outcome that intersects with other social inequities. Prior research has shown that in comparison to the general population, people experiencing homelessness have higher rates of infectious diseases, chronic illnesses, and mental-health disorders, along with disproportionately poorer outcomes. Hence, there is an urgent need to identify effective interventions to improve the lives of people living with homelessness. Objectives: The objective of this systematic review is to identify, appraise, and synthesise the best available evidence on the benefits and cost-effectiveness of interventions to improve the health and social outcomes of people experiencing homelessness. Search Methods: In consultation with an information scientist, we searched nine bibliographic databases, including Medline, EMBASE, and Cochrane CENTRAL, from database inception to February 10, 2020 using keywords and MeSH terms. We conducted a focused grey literature search and consulted experts for additional studies. Selection Criteria: Teams of two reviewers independently screened studies against our inclusion criteria. We included randomised control trials (RCTs) and quasi-experimental studies conducted among populations experiencing homelessness in high-income countries. Eligible interventions included permanent supportive housing (PSH), income assistance, standard case management (SCM), peer support, mental health interventions such as assertive community treatment (ACT), intensive case management (ICM), critical time intervention (CTI) and injectable antipsychotics, and substance-use interventions, including supervised consumption facilities (SCFs), managed alcohol programmes and opioid agonist therapy. Outcomes of interest were housing stability, mental health, quality of life, substance use, hospitalisations, employment and income. Data Collection and Analysis: Teams of two reviewers extracted data in duplicate and independently. We assessed risk of bias using the Cochrane Risk of Bias tool. We performed our statistical analyses using RevMan 5.3. For dichotomous data, we used odds ratios and risk ratios with 95% confidence intervals. For continuous data, we used the mean difference (MD) with a 95% CI if the outcomes were measured in the same way between trials. We used the standardised mean difference with a 95% CI to combine trials that measured the same outcome but used different methods of measurement. Whenever possible, we pooled effect estimates using a random-effects model. Main Results: The search resulted in 15,889 citations. We included 86 studies (128 citations) that examined the effectiveness and/or cost-effectiveness of interventions for people with lived experience of homelessness. Studies were conducted in the United States (73), Canada (8), United Kingdom (2), the Netherlands (2) and Australia (1). The studies were of low to moderate certainty, with several concerns regarding the risk of bias. PSH was found to have significant benefits on housing stability as compared to usual care. These benefits impacted both high- and moderate-needs populations with significant cimorbid mental illness and substance-use disorders. PSH may also reduce emergency department visits and days spent hospitalised. Most studies found no significant benefit of PSH on mental-health or substance-use outcomes. The effect on quality of life was also mixed and unclear. In one study, PSH resulted in lower odds of obtaining employment. The effect on income showed no significant differences. Income assistance appeared to have some benefits in improving housing stability, particularly in the form of rental subsidies. Although short-term improvement in depression and perceived stress levels were reported, no evidence of the long-term effect on mental health measures was found. No consistent impact on the outcomes of quality of life, substance use, hospitalisations, employment status, or earned income could be detected when compared with usual services. SCM interventions may have a small beneficial effect on housing stability, though results were mixed. Results for peer support interventions were also mixed, though no benefit was noted in housing stability specifically. Mental health interventions (ICM, ACT, CTI) appeared to reduce the number of days homeless and had varied effects on psychiatric symptoms, quality of life, and substance use over time. Cost analyses of PSH interventions reported mixed results. Seven studies showed that PSH interventions were associated with increased cost to payers and that the cost of the interventions were only partially offset by savings in medical- and social-services costs. Six studies revealed that PSH interventions saved the payers money. Two studies focused on the cost-effectiveness of income-assistance interventions. For each additional day housed, clients who received income assistance incurred additional costs of US$45 (95% CI, -$19, -$108) from the societal perspective. In addition, the benefits gained from temporary financial assistance were found to outweigh the costs, with a net savings of US$20,548. The economic implications of case management interventions (SCM, ICM, ACT, CTI) was highly uncertain. SCM clients were found to incur higher costs than those receiving the usual care. For ICM, all included studies suggested that the intervention may be cost-offset or cost-effective. Regarding ACT, included studies consistently revealed that ACT saved payers money and improved health outcomes than usual care. Despite having comparable costs (US$52,574 vs. US$51,749), CTI led to greater nonhomeless nights (508 vs. 450 nights) compared to usual services. Authors' Conclusions: PSH interventions improved housing stability for people living with homelessness. High-intensity case management and income-assistance interventions may also benefit housing stability. The majority of included interventions inconsistently detected benefits for mental health, quality of life, substance use, employment and income. These results have important implications for public health, social policy, and community programme implementation. The COVID-19 pandemic has highlighted the urgent need to tackle systemic inequality and address social determinants of health. Our review provides timely evidence on PSH, income assistance, and mental health interventions as a means of improving housing stability. PSH has major cost and policy implications and this approach could play a key role in ending homelessness. Evidence-based reviews like this one can guide practice and outcome research and contribute to advancing international networks committed to solving homelessness.

Formula-feeding and hypertrophic pyloric stenosis: is there an association? A case-control study.

BACKGROUND: The etiology of infantile hypertrophic pyloric stenosis (HPS) is not fully understood. The objective of this study was to determine whether formula-feeding is associated with increased incidence. METHODS: This case-control study included HPS cases and controls admitted between 1992 and 2012. Demographic data including feeding method were collected from patient charts and analyzed. RESULTS: We identified 882 HPS cases and 955 controls. The highest incidence of HPS presentation was in summer (P=0.0028). Infants with HPS were more likely to have been exclusively formula-fed, have a family history of HPS, and be male compared to infants in the control group (P<0.001); they were also more likely to live in rural areas, although not significantly so. After adjusting for family history, sex, place of residence, and season of presentation, exclusively formula-fed infants were 1.36 times more likely to develop HPS compared with exclusively breastfed infants (RR 1.36, 95% CI 1.18-1.57, P<0.005). CONCLUSIONS: Formula-feeding is associated with significantly increased risk of HPS. Further investigation may help to determine the components of formula that simulate hypertrophy of the pylorus muscle, or the components of breast milk that are protective, as well as other influencing factors. LEVEL OF EVIDENCE: 3b.

Resection for secondary malignancy of the pancreas.

OBJECTIVES: This study tried to clarify the role of pancreatic resection in the treatment of secondary malignancy with metastasis or local invasion to the pancreas in terms of surgical risk and survival benefit. METHODS: Data of secondary malignancy of the pancreas from our 19 patients and cases reported in the English literature were pooled together for analysis. RESULTS: There were 329 cases of resected secondary malignancy of the pancreas, including 241 cases of metastasis and 88 cases of local invasion. The most common primary tumor metastatic to the pancreas and amenable to resection was renal cell carcinoma (RCC) (73.9%). More than half (52.3%) of the primary cancers with local invasion to the pancreas were colon cancer, and nearly half (40.9%) were stomach cancer. The median metastatic interval was 84 months (7 years) for overall primary tumors and 108 months (9 years) for RCC. The 5-year survival for secondary malignancy of the pancreas after resection was 61.1% for metastasis and 58.9% for local invasion, with 72.8% for RCC metastasis, 69.0% for colon cancer, and 43.8% for stomach cancer with local invasion to the pancreas. CONCLUSIONS: Pancreatic resection should not be precluded for secondary malignancy of the pancreas because long-term survival could be achieved with acceptable surgical risk in selected patients.