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.

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.

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.

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.

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.

Feasibility, acceptability, and potential efficacy of an innovative postnatal home-based breastfeeding peer support programme in Hong Kong: a feasibility and pilot randomised controlled trial.

BACKGROUND: As suggested by the World Health Organization, breastfeeding peer support is being introduced worldwide to support women's breastfeeding needs. Evidence has shown that when such support is offered to women, the duration and exclusivity of breastfeeding is increased. We developed an innovative home-based intervention to sustain exclusive breastfeeding in Hong Kong. However, potential barriers must be addressed before a full randomised controlled trial (RCT) is conducted. The aim of this study was to determine the feasibility of a breastfeeding support programme with home-based visits from peer supporters over a six month period among postpartum Chinese women in Hong Kong. METHODS: We conducted a feasibility and pilot randomised controlled trial. Twenty primiparous women intending to breastfeed their healthy term singleton infant were recruited from a hospital in Kowloon, Hong Kong between February and March 2019. Participants were randomly allocated to the intervention or control group. Participants in the intervention group received five home-based visits with a peer supporter over a six month period, as well as standard care, whereas participants in the control group received standard care only. We assessed feasibility, compliance, and acceptability of the breastfeeding peer support programme. Other outcomes assessed were breastfeeding self-efficacy, duration, and exclusivity. RESULTS: It was feasible to recruit and train existing peer supporters, and peer supporters were able to deliver the intervention, which was acceptable to women, but rates of stopping the intervention and loss to follow-up were high. There was higher retention seen within the first month. Women interviewed at the end of the study reported that the intervention was positive. The cessation risk of any, and exclusive breastfeeding were not statistically different between the intervention and control groups. CONCLUSIONS: This study provided valuable information on feasibility of the trial design and intervention. Modifications to the intervention, such as targeting women with lower breastfeeding self-efficacy, or combining home visits with technology and telephone follow-up may be more appropriate in a larger trial. Implementing the programme early during the antenatal phase and tailoring peer support to most appropriately sustain exclusive breastfeeding and other feeding modes should be incorporated in a future home-based peer support arm. TRIAL REGISTRATION: NCT03705494 on 15 Oct 2018.

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.

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.

Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma.

Enhancing the efficacy of proteasome inhibitors (PI) is a central goal in myeloma therapy. We proposed that signaling-level responses after PI may reveal new mechanisms of action that can be therapeutically exploited. Unbiased phosphoproteomics after treatment with the PI carfilzomib surprisingly demonstrates the most prominent phosphorylation changes on splicing related proteins. Spliceosome modulation is invisible to RNA or protein abundance alone. Transcriptome analysis after PI demonstrates broad-scale intron retention, suggestive of spliceosome interference, as well as specific alternative splicing of protein homeostasis machinery components. These findings lead us to evaluate direct spliceosome inhibition in myeloma, which synergizes with carfilzomib and shows potent anti-tumor activity. Functional genomics and exome sequencing further support the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma.

Implementing an early feeding pathway post gastrostomy insertion reduces inpatient stay.

BACKGROUND: There is no consensus regarding optimal postoperative feeding strategy following gastrostomy insertion in children. The aim of this study was to determine whether implementing an early postoperative feeding pathway reduces length of stay (LOS) without increasing complications. METHODS: A retrospective case note review of all children having a new gastrostomy inserted during a one-year period prior to (July 2016-July 2017) and following (July 2017-July 2018) pathway introduction was performed. Children unable to follow the pathway for coexisting medical or nutritional reasons were excluded. The pathway comprised feeding 50% of normal feed 2 hours postprocedure, followed by 100% of normal feed at 5 and 8 h. Previously, patients were fed postoperatively according to surgeon preference. RESULTS: 116 cases met inclusion criteria, 55 prior to and 61 after pathway implementation. Children following the early feeding pathway had a shorter postoperative LOS than the historical group (median 28 vs 33 h, p < 0.003), while immediate (<72 h) and early (<30 day) complication rates were similar (8.2 vs 7.3%, p = 1.00 and 12 vs 16%, p = 0.59, respectively). CONCLUSIONS: Early postoperative feeding after gastrostomy insertion is safe and reduces LOS. TYPE OF STUDY: Quality improvement. LEVEL OF EVIDENCE: III.

Investigation the EMG Activities of Lower Limb Muscles When Doing Squatting Exercise in Water and on Land.

(1) Background: Squatting is one of the common closed-kinetic chain (CKC) exercises for knee rehabilitation. Some patients cannot perform squatting exercises on land occasionally due to knee pain. Several studies had suggested that lower limb muscle activities are lower in water than on land while performing CKC exercises. The purpose of this study is to investigate the surface electromyography (sEMG) activities of Rectus femoris (RF) and Biceps femoris (BF) muscles when doing a squatting exercise in water and on land. (2) Methods: This was a cross-sectional experimental study. A total of 20 healthy participants (10 males, 10 females) were recruited by convenience sampling. The sEMG of RF and BF muscles in water and on land were collected and the knee motions were videotaped. Participants were instructed to perform closed kinetic-chain back squatting exercises at a specific speed (30 beats per minute) in water and on land at angular speed of 45°/s. Eight repetitions of the squatting exercise (0-90° knee flexion) were performed. The mean percentage maximal voluntary contraction (%MVC) between two muscles was compared in two conditions. The %MVC of RF and BF muscles at different specific knee flexion angles (30°, 60° and 90° knee flexion) was also identified. (3) Result: Muscle activities of RF (p = 0.01) and BF (p < 0.01) muscles were significantly lower in water than on land. The %MVC of RF and BF muscles was found to be 15.01% and 10.68% lower in water than on land respectively. For different knee angle phases, the differences in %MVC between land and water had significant difference for both RF muscles and BF muscles. (4) Conclusion: This study found a difference of mean percentage MVC of RF and BF muscles between land and water in different phases of squatting. The water medium reduced the two muscles' activities to a similar extent. The result showed that the aquatic environment allows an individual to perform squatting with less muscle activation which may serve as an alternative knee exercise option for patients who encounter difficulty in land squatting due to lower limb muscle weakness or a high level of knee pain.

Intradetrusor injection of botulinum toxin A in children: a 10-year single centre experience.

PURPOSE: We evaluated the efficacy and safety outcomes of endoscopic intradetrusor botulinum toxin A (BTA) injections for the treatment of children with neuropathic bladder (NB) and non-neuropathic bladder (NNB) with or without detrusor overactivity in a single centre with a retrospective analysis. METHODS: For the period 2006-2015, children who received BTA in our hospital were analysed. They were divided into group 1, those with underlying NB and group 2, those without a clear neuropathic cause of symptoms (NNB). Data are given as percentages or medians (interquartile range). RESULTS: Over the study period, 52 children (28 boys, 54%) received BTA, 28 in group 1 (54%; 17 (61%) boys) and 24 in group 2 (46%; 11 (46%) boys). Age at first injection was 11.8 (9.5-14.4) years. After initial injection, 40 (77%) reported symptomatic improvement, 17 (43%) becoming dry. There was no significant difference in response to initial injection between groups (p = 0.11). Duration of improvement after first injection was 7 (5.8-14) months. Twenty-five (48%) had further injections, of whom 3 (12%) were initial non-responders. Ongoing improvement was reported in 20 (80%), 11 (44%) of whom were dry. There was no significant difference in overall response to injections between groups (p = 0.11). Of the 11 non-responders, none (0/3) improved after subsequent injection and 3 (27%) subsequently underwent major urological surgery. Of the 40 who responded, 2 (5%) underwent major surgery. CONCLUSION: BTA injection produced symptomatic improvement in 77% of our study population, with no significant differences in response between NB and NNB groups. In 95% of those who improved, major urinary tract procedures were avoided during the period studied. None of the initial non-responders improved after subsequent BTA injection. BTA injection is effective and reliable in the management of children with NB and NNB refractory to medical therapy.

Impact of immigration status on health behaviors and perceptions in cancer survivors.

BACKGROUND: Health behaviors including smoking cessation, physical activity (PA), and alcohol moderation are key aspects of cancer survivorship. Immigrants may have unique survivorship needs. We evaluated whether immigrant cancer survivors had health behaviors and perceptions that were distinct from native-born cancer survivors. METHODS: Adult cancer patients from Princess Margaret Cancer Centre were surveyed on their smoking, PA, and alcohol habits and perceptions of the effects of these behaviors on quality of life (QoL), 5-year survival, and fatigue. Multivariable models evaluated the association of immigration status and region-of-origin on behaviors and perceptions. RESULTS: Of the 784 patients, 39% self-identified as immigrants. Median time of survey was 24 months after histological diagnosis. At baseline, immigrants had trends toward not meeting Canadian PA guidelines or being ever-drinkers; patients from non-Western countries were less likely to smoke (aORcurrent  = 0.46, aORex-smoker  = 0.47, P = 0.02), drink alcohol (aORcurrent  = 0.22, aORex-drinker  = 0.52, P < 0.001), or meet PA guidelines (aOR = 0.44, P = 0.006). Among immigrants, remote immigrants (migrated ≥40 years ago) were more likely to be consuming alcohol at diagnosis (aOR = 5.70, P < 0.001) compared to recent immigrants. Compared to nonimmigrants, immigrants were less likely to perceive smoking as harmful on QoL (aOR = 0.58, P = 0.008) and survival (aOR = 0.56, P = 0.002), and less likely to perceive that PA improved fatigue (aOR = 0.62, P = 0.04) and survival (aOR = 0.64, P = 0.08). CONCLUSIONS: Immigrants had different patterns of health behaviors than nonimmigrants. Immigrants were less likely to perceive continued smoking as harmful and were less likely to be aware of PA benefits. Culturally tailored counselling may be required for immigrants who smoke or are physically sedentary at diagnosis.

Bittersweet tumor development and progression: Emerging roles of epithelial plasticity glycosylations.

Altered metabolism is one of the hallmarks of cancer. The best-known cancer metabolic anomaly is an increase in aerobic glycolysis, which generates ATP and other basic building blocks, such as nucleotides, lipids, and proteins to support tumor cell growth and survival. Epithelial plasticity (EP) programs such as the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are evolutionarily conserved processes that are essential for embryonic development. EP also plays an important role during tumor progression toward metastasis and treatment resistance, and new roles in the acceleration of tumorigenesis have been found. Recent evidence has linked EMT-related transcriptomic alterations with metabolic reprogramming in cancer cells, which include increased aerobic glycolysis. More recent studies have revealed a novel connection between EMT and altered glycosylation in tumor cells, in which EMT drives an increase in glucose uptake and flux into the hexosamine biosynthetic pathway (HBP). The HBP is a side-branch pathway from glycolysis which generates the end product uridine-5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc). A key downstream utilization of UDP-GlcNAc is for the post-translational modification O-GlcNAcylation which involves the attachment of the GlcNAc moiety to Ser/Thr/Asn residues of proteins. Global changes in protein O-GlcNAcylation are emerging as a general characteristic of cancer cells. In our recent study, we demonstrated that the EMT-HBP-O-GlcNAcylation axis drives the O-GlcNAcylation of key proteins such as c-Myc, which previous studies have shown to suppress oncogene-induced senescence (OIS) and contribute to accelerated tumorigenesis. Here, we review the HBP and O-GlcNAcylation and their putative roles in driving EMT-related cancer processes with examples to illuminate potential new therapeutic targets for cancer.

Association Between Clinician Specialization in Nursing Home Care and Nursing Home Clinical Quality Scores.

IMPORTANCE: While the number of prescribing clinicians (physicians and nurse practitioners) who provide any nursing home care remained stable over the past decade, the number of clinicians who focus their practice exclusively on nursing home care has increased by over 30%. OBJECTIVES: To measure the association between regional trends in clinician specialization in nursing home care and nursing home quality. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: Patients treated in 15,636 nursing homes in 305 US hospital referral regions between 2013 and 2016. MEASURES: Clinician specialization in nursing home care for 2012-2015 was measured using Medicare fee-for-service billings. Nursing home specialists were defined as generalist physicians (internal medicine, family medicine, geriatrics, and general practice) or advanced practitioners (nurse practitioners and physician assistants) with at least 90% of their billings for care in nursing homes. The number of clinicians was aggregated at the hospital referral region level and divided by the number of occupied Medicare-certified nursing home beds. Nursing Home Compare quality measure scores for 2013-2016 were aggregated at the HHR level, weighted by occupied beds in each nursing home in the hospital referral region. We measured the association between the number of nursing home specialists per 1000 beds and the clinical quality measure scores in the subsequent year using linear regression. RESULTS: An increase in nursing home specialists per 1000 occupied beds in a region was associated with lower use of long-stay antipsychotic medications and indwelling bladder catheters, higher prevalence of depressive symptoms, and was not associated with urinary tract infections, use of restraints, or short-stay antipsychotic use. CONCLUSIONS AND IMPLICATIONS: Higher prevalence of nursing home specialists was associated with regional improvements in 2 of 6 quality measures. Future studies should evaluate whether concentrating patient care among clinicians who specialize in nursing home practice improves outcomes for individual patients. The current findings suggest that prescribing clinicians play an important role in nursing home care quality.

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.