Building a baby-friendly community: Development, strategy, implementation and evaluation of a BFCI program.

AIM: The aim of the study was to investigate the impact of the use of baby-friendly community initiative (BFCI) model on various stakeholders in the community. DESIGN: Quasi-experimental research design. METHOD: The study was conducted in public premises and online workshops from April 2019 to September 2022. Participants were followed up for a period of 1 month, except for those employed at public premises. The program involved training based on an accredited BFCI framework to cultivate a breastfeeding-friendly attitude and knowledge. A paired sample t-test was used to examine breastfeeding attitude and knowledge scores before and after BFCI training among staff employed from public premises. An analysis of variance was conducted to examine the breastfeeding self-efficacy and attitude scores, measured repeatedly at different timepoints over 1-month timepoint (T0, T1 and T2) among pregnant and postpartum women. RESULTS: A total of 2340 perinatal women and 1339 staff from public premises were recruited. For staff, there was an increase in the mean score of breastfeeding knowledge and attitude by 5.8 and 6.1, respectively, at T1. Similarly, for perinatal women, there was an increase in the mean score of breastfeeding self-efficacy and attitude by 6.6 and 3.3, respectively, at T1. CONCLUSION: In summary, a BFCI model, with active community participation, accreditation and an award system, has been effective in promoting breastfeeding. Adapting the baby-friendly hospital initiative to local contexts and employing a social theory model can enhance breastfeeding promotion and improve infant health outcomes. Prioritizing culturally sensitive breastfeeding education is crucial for successful BFCI implementation. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Healthcare professionals should consider clients' culture and socio-economic backgrounds when providing breastfeeding education to maximize effectiveness. The target audience for breastfeeding education should be expanded to include various community stakeholders beyond families. IMPACT: What problem did the study address? This study addressed the problem of knowledge gaps among stakeholders in building a breastfeeding-friendly community, particularly in implementing a baby-friendly community initiative (BFCI) as part of a baby-friendly hospital initiative (BFHI). The research filled a service gap by providing effective interventions targeting community stakeholders and assessing the impact of a BFCI program on their knowledge and attitudes towards breastfeeding. What were the main findings? The findings highlighted the effectiveness of a BFCI program in enhancing breastfeeding knowledge and attitudes among frontline staff and increasing breastfeeding confidence among mothers. These findings contribute to the understanding of the program's impact on different stakeholders in the community. Where and on whom will the research have an impact? It impacts on global policymakers by providing insights for developing comprehensive guidelines for future BFCI implementations. It also contributes to the creation of a more baby-friendly community, benefiting breastfeeding families and their infants by promoting and supporting breastfeeding families. REPORTING METHOD: This study has adhered to relevant EQUATOR guidelines using the TREND reporting guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: This study provides an overview of the establishment of a localized BFCI program. It also opens up a new direction for the community to investigate BFCI strategies for community stakeholders. It also provides evidence to support other countries in following a similar process, as each country approaches becoming breastfeeding-friendly in its own unique way. TRIAL AND PROTOCOL REGISTRATION: No protocol.

Scaling Beyond Early Adopters: a Content Analysis of Literature and Key Informant Perspectives.

BACKGROUND: Innovations and improvements in care delivery are often not spread across all settings that would benefit from their uptake. Scale-up and spread efforts are deliberate efforts to increase the impact of innovations successfully tested in pilot projects so as to benefit more people. The final stages of scale-up and spread initiatives must contend with reaching hard-to-engage sites. OBJECTIVE: To describe the process of scale-up and spread initiatives, with a focus on hard-to-engage sites and strategies to approach them. DESIGN: Qualitative content analysis of systematically identified literature and key informant interviews. PARTICIPANTS: Leads from large magnitude scale-up and spread projects. APPROACH: We conducted a systematic literature search on large magnitude scale-up and spread and interviews with eight project leads, who shared their perspectives on strategies to scale-up and spread clinical and administrative practices across healthcare systems, focusing on hard-to-engage sites. We synthesized these data using content analysis. KEY RESULTS: Searches identified 1919 titles, of which 52 articles were included. Thirty-four discussed general scale-up and spread strategies, 11 described hard-to-engage sites, and 7 discussed strategies for hard-to-engage sites. These included publications were combined with interview findings to describe a fourth phase of the national scale-up and spread process, common challenges for spreading to hard-to-engage sites, and potential benefits of working with hard-to-engage sites, as well as useful strategies for working with hard-to-engage sites. CONCLUSIONS: We identified scant published evidence that describes strategies for reaching hard-to-engage sites. The sparse data we identified aligned with key informant accounts. Future work could focus on better documentation of the later stages of spread efforts, including specific tailoring of approaches and strategies used with hard-to-engage sites. Spread efforts should include a "flexible, tailored approach" for this highly variable group, especially as implementation science is looking to expand its impact in routine care settings.

The Effect of Dipeptidyl Peptidase-4 Inhibitors on Macrovascular and Microvascular Complications of Diabetes Mellitus: A Systematic Review.

BACKGROUND: The World Health Organization estimates that diabetes is the seventh leading cause of death. Uncontrolled diabetes may cause severe consequences such as cardiovascular (CV) events (myocardial infarction, stroke, or CV mortality), lower-extremity amputations, and end-stage renal disease. Microvascular complications include retinopathy, autonomic and peripheral neuropathy, nephropathy, and diabetic ulcers. Major CV outcomes trials that were by the Food and Drug Administration for all new antihyperglycemia medications for patients at high risk for CV events were recently completed for all 4 US-marketed dipeptidyl peptidase-4 (DPP-4) inhibitors. OBJECTIVE: To present a comprehensive review of the clinical trials that evaluate macrovascular and microvascular complications reported with DPP-4 inhibitors in patients with type 2 diabetes mellitus. METHODS: In this review, we analyzed published articles in PubMed and Ovid databases between January 2008 and September 2019 that evaluated the effect of DPP-4 inhibitors on macrovascular and microvascular complications in patients with type 2 diabetes mellitus. RESULTS: A total of 18 studies, which included randomized controlled trials and meta-analyses were assessed. Current evidence demonstrates that the addition of DPP-4 inhibitors to standard antihyperglycemic and CV risk reduction treatment has not shown CV benefit relative to placebo in contrast to recently published studies for other medications within the glucagon-like peptide 1 agonist and sodium-glucose co-transporter 2 inhibitor classes. Notably, the potential risk for heart failure hospitalizations may exist for saxagliptin, and this effect is not extrapolated as a class effect. Based on our review, DPP-4 inhibitors may not influence microvascular complications in patients with diabetes. However, some studies have shown that saxagliptin and linagliptin may slow down the progression of albuminuria in patients with type 2 diabetes mellitus. The overall quality of the studies included in this review was high due to the inclusion of randomized controlled trials and meta-analyses. CONCLUSIONS: DPP-4 inhibitors were found to have a neutral effect on macrovascular and microvascular complications, with the exception of saxagliptin, which may increase the risk for heart failure hospitalizations.

Patterns, perceptions and their association with changes in alcohol consumption in cancer survivors.

Continued consumption of alcohol after a cancer diagnosis is associated with poorer outcomes. We evaluated whether perceptions of the effects of continued alcohol use and receiving information on moderating alcohol reduced alcohol consumption in adult cancer survivors. A total of 509 cancer survivors were cross-sectionally surveyed at follow-up for their alcohol use before and after cancer diagnosis and perceptions of continued drinking. Multivariable logistic regression models evaluated factors associated with changes in alcohol consumption after diagnosis. Among 299 patients who were drinking alcohol at diagnosis (13% exceeding gender-specific guidelines), 52% reduced/ceased alcohol consumption 1 year after diagnosis. Patients perceiving that alcohol worsened their own (a) quality of life, (b) cancer-related fatigue or (c) overall survival were more likely (aORs = 2.43-3.35, p < 0.002) to reduce (moderating or quitting) their alcohol use 1 year after diagnosis. Only 14% of individuals currently drinking regularly recalled receiving information/counselling from healthcare providers on alcohol consumption (7% from oncologists). However, there was a significant fourfold to sixfold increase in cessation with such information/counselling (p < 0.01). Similar trends were observed in patients exceeding gender-specific guidelines. Perception of negative effects of alcohol use on their health by cancer survivors was associated with reducing harmful alcohol consumption. Counselling, especially from the oncologist, may play a significant role for reducing consumption.

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment.

The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling is thought to be a central component of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor Food and Drug Administration (FDA) approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Herein, we validated in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated xenograft models of myeloma, that tofacitinib showed efficacy in myeloma models. Furthermore, tofacitinib strongly synergized with venetoclax in coculture with bone marrow stromal cells but not in monoculture. Surprisingly, we found that ruxolitinib, an FDA approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. Transcriptome analysis and unbiased phosphoproteomics revealed that bone marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib reverses the growth-promoting effects of the tumor microenvironment. As tofacitinib is already FDA approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.

Patterns, perceptions, and perceived barriers to physical activity in adult cancer survivors.

PURPOSE: Physical activity (PA) during and after cancer treatment is associated with improved cancer- and non-cancer-related outcomes. We assessed for predictors of change in PA levels among cancer survivors. METHODS: Adult cancer survivors from a comprehensive cancer center completed a one-time questionnaire retrospectively assessing PA levels before, during, and after cancer treatment along with their perceptions of PA. Multivariable logistic regression models evaluated the association of clinico-demographics variables and perceptions of PA with changes in whether patients were meeting PA guidelines after cancer diagnosis. RESULTS: Among the 1003 patients, 319 (32%) met moderate to vigorous PA (MVPA) guidelines before diagnosis. Among those meeting guidelines before diagnosis, 50% still met guidelines after treatment; 12% not meeting MVPA guidelines initially met them after treatment/at follow-up. Among patients meeting guidelines before diagnosis, better ECOG performance status at follow-up, receiving curative therapy, and spending a longer time on PA initially were each associated with meeting guidelines at follow-up. After controlling for other variables, perceiving that PA improves quality of life (adjusted odds ratio, aOR = 11.09, 95%CI [1.42-86.64], P = 0.02) and overall survival (aOR = 8.52, 95%CI [1.12-64.71], P = 0.04) was each associated with meeting MVPA guidelines during/after treatment, in patients who did not meet guidelines initially. Only 13% reported receiving counseling, which was not associated with PA levels. Common reported barriers to PA included fatigue, lacking motivation, and being too busy. CONCLUSIONS: Patient perceptions of PA benefits are strongly associated with improving PA levels after a cancer diagnosis. Clinician counseling should focus on patient education and changing patient perceptions.

Targeting Interleukin-5 in Patients With Severe Eosinophilic Asthma: A Clinical Review.

Interleukin-5 (IL-5) is known to play a major role in the growth, differentiation, recruitment, and activation of eosinophils. The authors review the efficacy and safety of two IL-5-targeting agents used in the treatment of eosinophilic asthma.

Depression Quality of Care: Measuring Quality over Time Using VA Electronic Medical Record Data.

BACKGROUND: The Veterans Health Administration (VA) has invested substantially in evidence-based mental health care. Yet no electronic performance measures for assessing the level at which the population of Veterans with depression receive appropriate care have proven robust enough to support rigorous evaluation of the VA's depression initiatives. OBJECTIVE: Our objectives were to develop prototype longitudinal electronic population-based measures of depression care quality, validate the measures using expert panel judgment by VA and non-VA experts, and examine detection, follow-up and treatment rates over a decade (2000-2010). We describe our development methodology and the challenges to creating measures that capture the longitudinal course of clinical care from detection to treatment. DESIGN AND PARTICIPANTS: Data come from the National Patient Care Database and Pharmacy Benefits Management Database for primary care patients from 1999 to 2011, from nine Veteran Integrated Service Networks. MEASURES: We developed four population-based quality metrics for depression care that incorporate a 6-month look back and 1-year follow-up: detection of a new episode of depression, 84 and 180 day follow-up, and minimum appropriate treatment 1-year post detection. Expert panel techniques were used to evaluate the measure development methodology and results. Key challenges to creating valid longitudinal measures are discussed. KEY RESULTS: Over the decade, the rates for detection of new episodes of depression remained stable at 7-8 %. Follow-up at 84 and 180 days were 37 % and 45 % in 2000 and increased to 56 % and 63 % by 2010. Minimum appropriate treatment remained relatively stable over the decade (82-84 %). CONCLUSIONS: The development of valid longitudinal, population-based quality measures for depression care is a complex process with numerous challenges. If the full spectrum of care from detection to follow-up and treatment is not captured, performance measures could actually mask the clinical areas in need of quality improvement efforts.

The role of second-hand smoke exposure on smoking cessation in non-tobacco-related cancers.

BACKGROUND: Second-hand smoke (SHS) is a significant barrier to smoking cessation after a diagnosis of cancer in patients with lung as well as head and neck cancers. In the current study, the authors evaluated the effect of SHS on smoking cessation among patients with those cancers not traditionally perceived to be strongly associated with smoking. METHODS: Patients recruited from a single tertiary care center completed a self-administered questionnaire. Multivariate logistic regression and Cox proportional hazards models evaluated the association of sociodemographics, clinicopathological variables, and exposure to SHS with either smoking cessation or time to quitting. RESULTS: In all, 926 patients with diverse cancer subtypes completed the questionnaire. Of the 161 who were current smokers at the time of their cancer diagnosis, 48% quit after diagnosis. Lack of exposure to SHS at home was found to be associated with smoking cessation at any time after diagnosis (adjusted odd ratio, 4.28; 95% confidence interval, 1.56-11.78 [P =.005]), with similar trends noted 1 year after diagnosis (adjusted odds ratio, 2.56; 95% confidence interval, 0.91-7.22 [P =.08]). There was a significant inverse dose-response relationship between hours of SHS exposure at home and smoking cessation. Spousal and peer smoking were not found to be significantly associated with smoking cessation on multivariate analysis (P>.05). Kaplan-Meier analysis found that of patients who did quit smoking, 61% quit within 6 months of their cancer diagnosis. CONCLUSIONS: Exposure to SHS at home is a significant barrier to smoking cessation in patients whose cancers are not traditionally perceived as being related to tobacco. SHS should be a key consideration in the development of survivorship programs geared toward smoking cessation for all patients with cancer.

Effect of a hospital policy of not accepting free infant formula on in-hospital formula supplementation rates and breast-feeding duration.

OBJECTIVE: To investigate the effect of public hospitals in Hong Kong not accepting free infant formula from manufacturers on in-hospital formula supplementation rates and breast-feeding duration. DESIGN: Prospective cohort study. SETTING: In-patient postnatal units of four public hospitals in Hong Kong. SUBJECTS: Two cohorts of breast-feeding mother-infant pairs (n 2560). Cohort 1 (n 1320) was recruited before implementation of the policy to stop accepting free infant formula and cohort 2 (n 1240) was recruited after policy implementation. Participants were followed prospectively for 12 months or until they stopped breast-feeding. RESULTS: The mean number of formula supplements given to infants in the first 24 h was 2·70 (sd 3·11) in cohort 1 and 1·17 (sd 1·94) in cohort 2 (P<0·001). The proportion of infants who were exclusively breast-fed during the hospital stay increased from 17·7 % in cohort 1 to 41·3 % in cohort 2 (P<0·001) and the risk of breast-feeding cessation was significantly lower in cohort 2 (hazard ratio=0·81; 95 % CI 0·73, 0·90). Participants who non-exclusively breast-fed during the hospital stay had a significantly higher risk of stopping any or exclusive breast-feeding. Higher levels of formula supplementation also increased the risk of breast-feeding cessation in a dose-response pattern. CONCLUSIONS: After implementation of a hospital policy to pay market price for infant formula, rates of in-hospital formula supplementation were reduced and the rates of in-hospital exclusive breast-feeding and breast-feeding duration increased.

Are electronic nicotine delivery systems an effective smoking cessation tool?

BACKGROUND: Recent studies have estimated that 21% of all deaths over the past decade are due to smoking, making it the leading cause of premature death in Canada. To date, many steps have been taken to eradicate the global epidemic of tobacco smoking. Most recently, electronic nicotine delivery systems (ENDS) have become a popular smoking cessation tool. ENDS do not burn or use tobacco leaves, but instead vapourize a solution the user then inhales. The main constituents of the solution, in addition to nicotine when nicotine is present, are propylene glycol, with or without glycerol and flavouring agents. Currently, ENDS are not regulated, and have become a controversial topic. OBJECTIVES: To determine whether ENDS are an effective smoking cessation tool. METHODS: A systematic literature search was conducted in February 2015 using the following databases: PubMed, Scopus and Web of Science Core Collection. Randomized controlled trials were the only publications included in the search. A secondary search was conducted by reviewing the references of relevant publications. RESULTS: After conducting the primary and secondary search, 109 publications were identified. After applying all inclusion and exclusion criteria through abstract and full-text review, four publications were included in the present literature review. A low risk of bias was established for each included study using the Cochrane Collaboration risk of bias evaluation framework. DISCUSSION: The primary outcome measured in all studies was self-reported abstinence or reduction from smoking. In three of the four studies, self-reported abstinence or reduction from smoking was verified by measuring exhaled carbon monoxide. In the remaining study, the primary outcome measured was self-reported desire to smoke and measured desire to smoke. All four studies showed promise that ENDS are an effective smoking cessation tool. CONCLUSIONS: While all publications included in the present review revealed that ENDS are effective smoking cessation aid, further evaluation of the potential health effects in long-term use of ENDS remains vital.

HISTORIQUE: Selon les études récentes, 21 % de tous les décès depuis dix ans sont attribuables au tabagisme, ce qui en fait la principale cause de décès prématurés au Canada. Jusqu'à présent, de nombreuses mesures ont été prises pour éradiquer l'épidémie mondiale de tabagisme. Récemment, les systèmes électroniques de délivrance de nicotine (SÉDN) sont devenus un outil populaire d'abandon du tabac. Les SÉDN ne brûlent ni n'utilisent de feuilles de tabac, mais vaporisent une solution que le consommateur inhale. Les principaux éléments de la solution, en plus de la nicotine lorsque le système en contient, sont le propylèneglycol, accompagné ou non de glycérol et de substances aromatisantes. Les SÉDN ne sont pas réglementés, mais sont devenus controversés. OBJECTIFS: Déterminer si les SÉDN sont un outil efficace d'abandon du tabac. MÉTHODOLOGIE: Les chercheurs ont effectué une analyse bibliographique systématique en février 2015 à l'aide des bases de données suivantes : PubMed, Scopus et Web of Science Core Collection. Ils ont inclus seulement les essais aléatoires et contrôlés dans leur recherche. Dans une recherche secondaire, ils ont analysé les références des publications pertinentes. RÉSULTATS: Après avoir terminé les recherches primaire et secondaire, les chercheurs ont extrait 109 publications. Après avoir appliqué tous les critères d'inclusion et d'exclusion à l'analyse des résumés et des textes intégraux, ils ont intégré quatre publications à la présente analyse bibliographique. À l'aide du cadre d'évaluation du risque de biais de la Collaboration Cochrane, ils ont établi que chaque étude s'associait à un faible risque de biais. EXPOSÉ: Le résultat clinique primaire mesuré dans les études était une abstinence ou une réduction autodéclarée du tabagisme. Dans trois des quatre études, l'abstinence ou la réduction autodéclarée du tabagisme était mesurée par le monoxyde de carbone expiré. Dans la dernière étude, le résultat clinique primaire était le désir autodéclaré de fumer et le désir mesuré de fumer. Les quatre études ont révélé que les SÉDN sont un outil efficace d'abandon du tabac. CONCLUSIONS: Toutes les publications incluses dans la présente analyse ont révélé que les SÉDN sont des outils d'abandon du tabac, mais il demeure essentiel d'en évaluer davantage les effets potentiels à long terme sur la santé.

Effectiveness of a home-based peer support programme for Chinese mothers with low breastfeeding self-efficacy to increase the exclusivity and duration of breastfeeding: study protocol of a randomised control trial.

INTRODUCTION: Breastfeeding is associated with many health benefits for both women and their newborns. Exclusive breastfeeding has been recommended for at least 6 months to optimise infant growth, development and health. In addition to standard care, community-based peer support is recommended to help mothers improve breastfeeding. A recent survey reveals that the rate of exclusive breastfeeding at 6 months post partum in Hong Kong is low, and half of all breastfeeding mothers never exclusively breastfeed. Taking into account the local practice for women to stay home during the first month post partum and social isolation during and post-COVID-19 pandemic, a home-based peer support programme with the aid of Zoom or Facetime is proposed. This study aims to evaluate the effectiveness of a home-based breastfeeding peer support programme in improving breastfeeding practices and achieving exclusive breastfeeding rate among women with low breastfeeding self-efficacy. METHODS AND ANALYSIS: The study is a two-armed randomised control trial and will include a total of 442 participants. Potential cases will be recruited and screened at four postnatal wards in Hong Kong public hospital. Eligible and consented cases will be randomly allocated into intervention or control groups at a 1:1 ratio. Control group (n=221) will receive standard care, while the intervention group (n=221) will receive home-based peer support as well as standard care. Trained peer counsellors will provide breastfeeding-related support through Zoom or Facetime at 10 days and 1 month post partum. Telephone follow-ups will be conducted at 1 month, 2 months, 3 months and 6 months post partum. Breastfeeding status, mother's breastfeeding self-efficacy and postpartum depression will be assessed and compared between the two arms. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Institutional Review Board of the University of Hong Kong and Hospital Authority Hong Kong West Cluster (UW 20-564). The findings will be updated in trial registries and disseminated in peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT04621266.

Evaluation of the Safety and Tolerability of Sodium-Glucose Co-transporter 2 Inhibitors in the Older Population: A Systematic Review.

Objective The objective of this systematic review was to evaluate adverse effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors in older people. Data Sources Articles in PubMed and EBSCOhost-Medline databases between January 2011 and 2021 were analyzed. Search terms were SGLT2 inhibitor, SGLT2 inhibitors, geriatric/elderly/older people, and safety/ adverse drug reaction/tolerability. Meta-analyses, systematic reviews, review articles, journal clubs, articles that did not address the research question, excluded patients 65 years of age and older, had an updated article available, did not stratify by age group, or were a commentary on a cohort study were excluded. Data Synthesis The search resulted in 113 articles. There were 62 duplicates removed, and 30 excluded based on the abstract. Of the 32 articles remaining, 19 were removed for not meeting the research question or meeting exclusion criteria. A total of 13 studies, including randomized controlled trials, cohort studies, and case reports, were assessed. Conclusion Current evidence demonstrates that patients taking SGLT2 inhibitors and diuretics were more likely to experience volume depletion. Findings suggest that risk of UTI was highest when the patient's age is 75 years or older. Some studies indicated that risk of genital mycotic infection is prevalent in older people. Use of SGLT2 inhibitors in the older population was not associated with a higher risk of developing diabetic ketoacidosis. Use of SGLT2 inhibitors appears to be relatively safe in older people. The risk of side effects may be decreased by considering concomitant medications. Randomized controlled trials assessing safety of SGLT2 inhibitors in the older population is still warranted.

Griseofulvin Radiosensitizes Non-Small Cell Lung Cancer Cells and Activates cGAS.

Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome clustering (CC) inhibition (CCi) would preferentially radiosensitize non-small cell lung cancer (NSCLC). Griseofulvin (GF; FDA-approved treatment) inhibits CC, and combined with radiation treatment (RT), resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and radiation treatment resulted in a significant tumor growth delay. Both GF and radiation treatment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radioresistant cells that was dependent on cGAS. In conclusion, GF increased radiation treatment efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, radiation treatment, and immunotherapy could be a promising strategy to treat NSCLC.

Behavioral interventions for improving sleep outcomes in menopausal women: a systematic review and meta-analysis.

IMPORTANCE: Perimenopausal and postmenopausal women commonly report sleep disruption and insomnia. Behavioral interventions may be safe alternatives for patients who are unwilling to begin pharmacological treatments because of adverse effects, contraindications, or personal preference. OBJECTIVE: The primary objective is to assess the efficacy of behavioral interventions on sleep outcomes among perimenopausal and postmenopausal women, as measured using standardized scales and objective methods (polysomnography, actigraphy). The secondary objective is to evaluate the safety of these methods through occurrence of adverse events. EVIDENCE REVIEW: Searches were performed within MEDLINE (OVID interface, 1946 onward), Embase (OVID interface, 1974 onward), Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Web of Science (Core collection) using a search strategy developed in consultation with a health sciences librarian. Title/abstract and full-text screenings were performed in duplicate, and relevant studies were selected based on inclusion and exclusion criteria set to identify randomized controlled trials evaluating the effects of behavioral interventions on sleep quality. Risk of bias assessments were done using the Cochrane Risk of Bias 2 tool, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of the body of evidence. Data were pooled in a meta-analysis using a random-effects model. FINDINGS: Nineteen articles reporting results from 16 randomized controlled trials were included, representing a total of 2,108 perimenopausal and postmenopausal women. Overall, behavioral interventions showed a statistically significant effect on sleep outcomes (standardized mean difference [SMD], -0.62; 95% confidence interval [CI], -0.88 to -0.35; I2 = 93.4%). Subgroup analyses revealed that cognitive behavioral therapy (SMD, -0.40; 95% CI, -0.70 to -0.11; I2 = 72.7%), physical exercise (SMD, -0.57; 95% CI, -0.94 to -0.21; I2 = 94.0%), and mindfulness/relaxation (SMD, -1.28; 95% CI, -2.20 to -0.37; I2 = 96.0%) improved sleep, as measured using both subjective (eg, Pittsburg Sleep Quality Index) and objective measures. Low-intensity (SMD, -0.91; 95% CI, -1.59 to -0.24; I2 = 96.8) and moderate-intensity exercise (SMD, -0.21; 95% CI, -0.34 to -0.08; I2 = 0.0%) also improved sleep outcomes. No serious adverse events were reported. Overall risk of bias ranged from some concern to serious, and the certainty of the body of evidence was assessed to be of very low quality. CONCLUSIONS AND RELEVANCE: This meta-analysis provides evidence that behavioral interventions, specifically, cognitive behavioral therapy, physical exercise, and mindfulness/relaxation, are effective treatments for improving sleep outcomes among perimenopausal and postmenopausal women.

Cost-Effectiveness of Laparoscopic and Open Pediatric Inguinal Hernia Repair.

Aim: Laparoscopic inguinal hernia (IH) repair is an alternative to open surgery. A potential advantage of laparoscopic repair is prevention of contralateral metachronous hernia although some studies report higher recurrence rate. We aim to determine the cost-effectiveness of open versus laparoscopic IH repair taking into account metachronous and recurrence rates. Methods: Retrospective single-center study of children (<5 years) undergoing elective open or laparoscopic repair for a unilateral IH between February 2018 and October 2019. Ten cases in each of four groups were included (open day case, open overnight, laparoscopic day case, and laparoscopic overnight). Cases incurring a higher cost due to comorbidities or additional procedure were excluded. Patient-level information and costing system data were obtained from the hospital finance. Mean (standard deviation [SD]) procedural cost was compared for open and laparoscopic procedures. A financial model was created factoring metachronous and recurrent rates. Results: Cost of open day case repair was £1866.24 (SD: 311.15) compared with £2210.13 (SD: 391.36) for day case laparoscopic repair. For overnight repair, cost of open was £2442.82 (SD: 497.05) compared with £2585.35 (SD: 384.66) for laparoscopic. On calculating the cost-effectiveness point using the difference in metachronous and recurrence rate between the two procedures, laparoscopic is more cost-effective than open day case repair at 18.43%. For overnight repair, the difference rate is 5.84%. Conclusion: Our data suggest that based on metachronous and recurrence rates in the current literature, laparoscopic IH repair is more cost-effective than open repair for cases requiring overnight stay, whereas for day case procedures open IH repair is more cost-effective.

Allosteric HSP70 inhibitors perturb mitochondrial proteostasis and overcome proteasome inhibitor resistance in multiple myeloma.

Proteasome inhibitor (PI) resistance remains a central challenge in multiple myeloma. To identify pathways mediating resistance, we first mapped proteasome-associated genetic co-dependencies. We identified heat shock protein 70 (HSP70) chaperones as potential targets, consistent with proposed mechanisms of myeloma cells overcoming PI-induced stress. We therefore explored allosteric HSP70 inhibitors (JG compounds) as myeloma therapeutics. JG compounds exhibited increased efficacy against acquired and intrinsic PI-resistant myeloma models, unlike HSP90 inhibition. Shotgun and pulsed SILAC mass spectrometry demonstrated that JGs unexpectedly impact myeloma proteostasis by destabilizing the 55S mitoribosome. Our data suggest JGs have the most pronounced anti-myeloma effect not through inhibiting cytosolic HSP70 proteins but instead through mitochondrial-localized HSP70, HSPA9/mortalin. Analysis of myeloma patient data further supports strong effects of global proteostasis capacity, and particularly HSPA9 expression, on PI response. Our results characterize myeloma proteostasis networks under therapeutic pressure while motivating further investigation of HSPA9 as a specific vulnerability in PI-resistant disease.

Impact of baby-friendly hospital practices on breastfeeding in Hong Kong.

BACKGROUND: The World Health Organization (WHO) developed the Baby-Friendly Hospital Initiative to improve hospital maternity care practices that support breastfeeding. In Hong Kong, although no hospitals have yet received the Baby-Friendly status, efforts have been made to improve breastfeeding support. The aim of this study was to examine the impact of Baby-Friendly hospital practices on breastfeeding duration. METHODS: A sample of 1,242 breastfeeding mother-infant pairs was recruited from four public hospitals in Hong Kong and followed up prospectively for up to 12 months. The primary outcome variable was defined as breastfeeding for 8 weeks or less. Predictor variables included six Baby-Friendly practices: breastfeeding initiation within 1 hour of birth, exclusive breastfeeding while in hospital, rooming-in, breastfeeding on demand, no pacifiers or artificial nipples, and information on breastfeeding support groups provided on discharge. RESULTS: Only 46.6 percent of women breastfed for more than 8 weeks, and only 4.8 percent of mothers experienced all six Baby-Friendly practices. After controlling for all other Baby-Friendly practices and possible confounding variables, exclusive breastfeeding while in hospital was protective against early breastfeeding cessation (OR: 0.61; 95% CI: 0.42-0.88). Compared with mothers who experienced all six Baby-Friendly practices, those who experienced one or fewer Baby-Friendly practices were almost three times more likely to discontinue breastfeeding (OR: 3.13; 95% CI: 1.41-6.95). CONCLUSIONS: Greater exposure to Baby-Friendly practices would substantially increase new mothers' chances of breastfeeding beyond 8 weeks postpartum. To further improve maternity care practices in hospitals, institutional and administrative support are required to ensure all mothers receive adequate breastfeeding support in accordance with WHO guidelines.

The hexosamine biosynthetic pathway and cancer: Current knowledge and future therapeutic strategies.

The hexosamine biosynthetic pathway (HBP) is a glucose metabolism pathway that results in the synthesis of a nucleotide sugar UDP-GlcNAc, which is subsequently used for the post-translational modification (O-GlcNAcylation) of intracellular proteins that regulate nutrient sensing and stress response. The HBP is carried out by a series of enzymes, many of which have been extensively implicated in cancer pathophysiology. Increasing evidence suggests that elevated activation of the HBP may act as a cancer biomarker. Inhibition of HBP enzymes could suppress tumor cell growth, modulate the immune response, reduce resistance, and sensitize tumor cells to conventional cancer therapy. Therefore, targeting the HBP may serve as a novel strategy for treating cancer patients. Here, we review the current findings on the significance of HBP enzymes in various cancers and discuss future approaches for exploiting HBP inhibition for cancer treatment.