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The Weight of Cardiovascular Diseases: Addressing the Global Cardiovascular Crisis Associated with Obesity
Get PDFObesity is a growing global epidemic with significant implications for cardiovascular diseases (CVD). It couples as an independent risk factor and driver for multiple pathways leading to CVDs. Here we examine obesity's impact on CVD and propose actionable strategies. Data from the NCD Risk Factor Collaboration (NCD-RisC), Global Burden of Disease (GBD) survey, and regional health surveys databases were used. We examined trends in obesity prevalence and CVD mortality attributable to high body mass index (BMI), disaggregated by sex, geography, socioeconomic status, and urban-rural residence. Evidence from national policy initiatives and clinical management guidelines was also reviewed. As of 2022, over 1 billion people globally were living with obesity. Since 1990 the age-standardised obesity prevalence has doubled among women (from 8.8% to 18.5%) and tripled among men (from 4.8% to 14%). Globally, the number of annual CVD deaths attributable to high BMI (25 kg/m2 or over) more than doubled between 1990 and 2021, reaching 1.9 million in 2021. Reducing global obesity to 2019 levels could save an estimated US$2.2 trillion annually by 2060. Positive steps have been made in recent years, with the implementation of several global, national and local initiatives that show promise in tackling obesity and CVDs, in addition to the emergence of potentially game-changing medical interventions, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs). Yet, to tackle obesity and associated CVD, there is a need for a holistic approach across clinical and public health interventions that accounts for the multiple determinants of obesity. We recommend the implementation of evidence-based, cost-effective public health measures, and the incorporation of obesity-specific recommendations into cardiovascular guidelines. Addressing the global cardiovascular crisis linked to obesity will require coordinated efforts from policymakers, healthcare systems, and global health organisations
Pregnant and breastfeeding women concerns during a group B Streptococcus phase ll clinical trial: A qualitative study in Kampala, Uganda
Get PDFDespite evidence that maternal vaccines can contribute to reduction of neonatal infections, vaccine hesitancy is a challenge in many low- and middle-income countries like Uganda. We conducted in-depth interviews with pregnant women and focus group discussions with breastfeeding women who were part of a Group B Streptococcus (GBS) clinical trial. We explored the women's concerns about vaccination and their reasons for being hesitant to take vaccines before they joined the trial. Women aged 18-39 were randomly selected from follow-up lists during the study period. Data were analysed thematically. All the women had been hesitant about joining the trial because of fear of possible vaccine side effects. A lack of knowledge on maternal vaccines, rumours and stigma in the community as well the need to follow study procedures were other concerns. Several women were concerned about their male partner view of their trial participation because using a trial vaccine meant taking a decision on behalf of the foetus. Pregnant women's involvement in clinical trials of maternal immunisation requires engagement with their families and community stakeholders, including local leaders and health workers, to ensure people understand what maternal vaccines are and why trials with pregnant women are required
Extended pharmacological thromboprophylaxis and clinically relevant venous thromboembolism after major abdominal and pelvic surgery: international, prospective, propensity score-weighted cohort study.
Get PDFBACKGROUND: There is low-certainty evidence on the impact of extended pharmacological prophylaxis on venous thromboembolism-associated morbidity and mortality. The aim of this study was to determine the efficacy and safety of extended prophylaxis after major abdominopelvic surgery for the prevention of clinically relevant venous thromboembolism after hospital discharge. METHODS: CArdiovaSCulAr outcomes after major abDominal surgEry (CASCADE) was a prospective, international, cohort study into which consecutive adult patients undergoing major abdominopelvic surgery were enrolled (January-May 2022). Extended prophylaxis was considered at least 28 days of anticoagulant prescription after surgery. The primary efficacy outcome was clinically relevant venous thromboembolism and the primary safety outcome was clinically relevant bleeding within 30 days after surgery (European Medicines Agency definitions). The independent association of these outcomes with extended prophylaxis was explored using mixed-effects logistic regression and propensity score weighting. RESULTS: A total of 11 571 patients (median age of 58.0 years; 6399 (55.3%) women) from 29 countries were included. The extended prophylaxis prescription rate was 31.7% (3670 patients). The post-discharge venous thromboembolism and bleeding rates were 0.1% (12 patients) and 0.7% (85 patients) respectively. After weighting, extended prophylaxis was not significantly associated with increased bleeding risk (OR 1.07 (95% c.i. 0.64 to 1.81); P = 0.792) or decreased venous thromboembolism incidence, both in the overall cohort (OR 1.13 (95% c.i. 0.33 to 3.90); P = 0.848) and in a subgroup analysis of patients undergoing complex major surgery and with active cancer (OR: 1.36 (95% c.i. 0.33 to 5.57); P = 0.669). CONCLUSION: In modern practice, the incidence of postoperative venous thromboembolism is low. Extended prophylaxis appears safe, yet the clinical efficacy remains uncertain. Further work is required to define patients who stand to benefit
Outcome of Tetralogy of Fallot Through Initial Palliation and Surgical Repair
Get PDFTetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease, frequently diagnosed prenatally. To enhance understanding, we reviewed 18 years of our institutional outcomes for patients with classic ToF. There were 410 patients of whom 233/410 (56.8%) were diagnosed prenatally. A genetic abnormality was diagnosed in 38/410 (9.3%), most commonly 22q11.2 microdeletion (43.6%). There were 10/410 (2.4%) deaths in the neonatal period prior to any cardiac intervention. Prior to complete ToF repair, 66/400 (16.5%) of patients required cardiac procedures, in 15 in the first week after birth. Babies with an antenatal diagnosis were more likely to require at least one procedure before complete ToF repair than those with a postnatal diagnosis (p = 0.039). There was a trend to shorter median length of stay in patients with RVOT stent (median 5.4 days) or duct stenting (median 4.2 days) versus BTT shunt (median 8 days). Complete ToF repair was undertaken in 396/410 at a median age of 6 months (IQR: 4.0–8.0 months), with a 30-day postoperative survival rate of 99.5%. The actuarial survival for the whole group (n = 410) of 410 patients was 98.5% at 30 days, 96.2% at 1 year, and 95.2% at 3 years of age. Following complete surgical repair, reintervention was required in 25% of cases: 3.3% at 30 days, 10.6% at 1 year, and 19.2% at 5 years. The freedom from reintervention was 89.4% after 1 year and 80.8% after 5 years. There were no deaths beyond 2.5 years post-repair. In conclusion, ToF can be repaired with a low procedural mortality rate and promising long-term survival outcomes, but there may be pre-procedural deaths and there is a likelihood of requiring reinterventions during follow-up
The hidden workload study protocol: a national mixed-methods analysis of general practice workload and local demographics
Get PDFBackground
General practice workload is increasing. Routinely reported NHS data describes workload in relation to numbers of appointments and clinicians delivering appointments. However, “hidden” aspects of general practice workload, such as administrative and supervisory tasks, are not measured.
Aims
The Hidden Workload Study will examine the full range of tasks that general practice clinicians undertake daily and investigate how workload varies according to clinical role and practice demographics. Participants’ lived experience of workload will also be explored through interviews.
Design & setting
Utilising the Primary Care Academic CollaboraTive’s membership and collaborative methodology, mixed quantitative and qualitative methods will be used. All clinicians working in English general practice, including general practitioners of all grades, resident doctors, nurses, physician associates, pharmacists and other allied healthcare professionals will be eligible, aiming for>500 participants across>75 practices.
Method
Participants will collect data on a randomly allocated day in late 2024/early 2025. Using a data collection form and timers, participants will record their planned work schedule and then all tasks they complete, including all clinical, administrative, and supervisory tasks, and breaks. Practice demographic data will be collected from NHS Fingertips. For the qualitative arm, 15-20 semi-structured qualitative interviews will also be carried out. Quantitative data will be described according to clinical role and practice demographics, and interviews transcribed and reflexively analysed.
Conclusion
The Hidden Workload Study will provide a comprehensive mixed methods analysis of contemporary general practice workload. Potential explanations for workload variations will be explored, informing future service provision and workforce planning
Comparing quality of life after robot assisted versus open radical cystectomy: A systematic review
Get PDFBackground
Bladder cancer is a common malignancy in both sexes. Robot-assisted approaches are increasingly used in its surgical management. Radical cystectomy can significantly affect health-related quality of life (HRQoL), typically assessed using patient-reported outcome measures (PROMs) that capture patients’ physical, psychological, and social well-being.
Objectives
To systematically compare HRQoL and functional outcomes following robot-assisted versus open radical cystectomy (RARC vs. ORC) for bladder cancer, and to evaluate the methodologies employed, including PROMs and postoperative assessment timepoints.
Methods
A systematic search of CENTRAL, Embase, PubMed, and Scopus (2000–2025) was performed for randomised and non-randomised studies comparing HRQoL outcomes after RARC and ORC. Eligible studies reporting PROM-based HRQoL were included. Data were extracted on patient characteristics, PROMs, and outcome domains, and synthesised descriptively.
Results
Nine studies involving 1,575 patients met inclusion criteria. Seven HRQoL domains were identified, assessed using 18 PROMs; the EORTC QLQ-C30 was most frequently applied (n = 4). HRQoL was typically assessed at 3, 6, and 12 months, with only one study extending beyond 12 months. Functional assessment was limited: one study employed the Internation Index of Erectile Function (IIEF-5) for male erectile function, none assessed female sexual function, and one reported objective continence outcomes. Across studies, no statistically significant differences in HRQoL were observed between RARC and ORC. However, heterogeneity in PROMs, inconsistent outcome reporting, and high risk of bias limited comparability.
Conclusions
Current evidence does not demonstrate a HRQoL advantage of RARC over ORC. Standardisation of PROMs, consistent follow-up intervals, and inclusion of functional domains are essential to strengthen comparative evidence and inform the role of RARC as a potential new standard of care
Estimated extent of purchasing of antibiotics without a prescription from community pharmacies in a rural province in South Africa and the implications
No full textBackground: Antimicrobial resistance is a considerable global health threat especially among low- and middle-income countries, exacerbated by considerable inappropriate dispensing of antibiotics. There have though been concerns with variable levels of dispensing of antibiotics without a prescription in South Africa. Consequently, a need to comprehensively estimate current levels of dispensing of antibiotics without a prescription, which was the aim of this study.
Methods: Administer a previously piloted questionnaire to all currently operating community pharmacies in a rural province, where dispensing of antibiotics without a prescription is likely to be greatest. The questionnaire included data on the estimated prevalence of antibiotics dispensed, their class and indication, and whether dispensed without a prescription. Community pharmacies were categorized into three: Independent, Chain and Franchise.
Results: 128/169 (75.7%) operational pharmacies participated, with independent pharmacies representing the majority (60.9%). There was a 78.3% response rate from 400 distributed questionnaires, including 106 pharmacists (33.9%) and 207 pharmacist assistants (66.1%) from 128 pharmacies. Antibiotics accounted for 47.9% (95% CI: 47.2%-48.6%) of all medicines dispensed. Penicillins were the most prevalent antibiotic dispensed (41.1%). Almost half (47.2%) of the antibiotics dispensed included macrolides, fluoroquinolones and cephalosporins, which are typically antibiotics from the Watch group. Sexually transmitted infections (33.5%) and upper respiratory tract infections (25.8%) were the most frequent indications for antibiotic dispensing. Overall, 69.3% of 128 participating pharmacies in this rural province in South Africa admitted to dispensing antibiotics without a prescription in the past 14 days, principally among independent pharmacies (98.7%). However, estimates suggest only 8.6% of the total volume of antibiotics being dispensed were dispensed without a prescription among the 88 community pharmacies admitting to this practice in the past 3 days. Encouragingly, 98.1% of community pharmacists and 97.6% of pharmacist assistants indicated they always or mostly offered symptomatic relief before dispensing antibiotics without a prescription to patients with self-limiting conditions.
Conclusion: There were considerable concerns regarding the prescribing and dispensing of antibiotics in this rural province including Watch antibiotics. This included the number of community pharmacies, especially independent pharmacies, where patients could purchase antibiotics without a prescription. Multiple strategies involving all key stakeholder groups are need to improve future antibiotic use across South Africa and reduce AMR
Mutations in RNU4ATAC Are Associated With Chilblain‐Like Lesions and Enhanced Type I Interferon Signalling
Get PDFEpigenetic control of stress and environmental enrichment interplay on anxiety and prefrontal cortex BDNF expression
No full textDespite widespread recognition of the detrimental effects of chronic stress in developing stress-related psychopathologies, the interplay between environmental enrichment (EE) and chronic stress, along with their underlying mechanisms, remains poorly understood. Chronic stress disrupts brain-derived neurotrophic factor (BDNF) signalling pathways in the prefrontal cortex (PFC) and promotes epigenetic modifications that contribute to the pathogenesis of depression and anxiety disorders. Environmental enrichment (EE) has also been investigated for its effects on BDNF expression and epigenetic regulation, with evidence suggesting a possible role in modulating vulnerability to stress-related psychopathologies. Here, we investigated the impact of subthreshold chronic unpredictable mild stress (CMS) on mice pre-housed in EE conditions, examining anxiety-like behaviour, corticosterone levels, PFC Bdnf expression, BDNF protein levels, and DNA methylation profiles. We also explored whether the effects of CMS on EE-housed mice are mediated by DNA methylation mechanisms. CMS precipitated anxiety-like behaviour in EE-housed mice, but not in non-enriched controls. This phenotype was attenuated by systemic administration of the DNA methylation inhibitor 5-aza-2’-deoxycytidine, suggesting an epigenetic mechanism. While prolonged EE alone elevated plasma corticosterone levels, this was suppressed when EE was combined with CMS. EE followed by CMS downregulated Bdnf exons I, II, IV, and IX mRNA expression in the PFC. No changes in DNA methylation profile were detected at exon IX. While no effect was detected on BDNF protein levels, 5-azaC reduced BDNF specifically in EE-housed mice. These findings shed light on the emotional behavioural consequences and the molecular and epigenetic mechanisms underlying the interplay between CMS and EE
What Should Be Discussed When Considering a Vaginal Birth? A Delphi Consensus Study
Get PDFObjective
Spontaneous vaginal births are often the presumed choice, representing 45% of UK births. However, information about benefits and risks is inconsistently given, impacting decision‐making and experience. A Core Information Set (CIS) is an agreed set of information points discussed prior to a decision. We aimed to develop a CIS for vaginal birth.
Design
A Delphi study was used to create the CIS. Information points were identified from a literature search, patient leaflets, interviews, and a survey. These informed a two‐round Delphi survey, where stakeholders rated item importance. Items rated critically important by ≥ 80% of parents or professionals, and of limited importance by < 15%, progressed to consensus meetings, where 20 parents and professionals discussed retained items. The final CIS was populated with an engagement group ensuring accessibility.
Setting
The study took place in the UK, with participants recruited online.
Population
Pregnant and postnatal women, birth partners, healthcare professionals, medicolegal professionals, and representatives from relevant organizations.
Main Outcome
A CIS for vaginal birth.
Results
77 information items were identified. In round 1 (631 participants) of the Delphi Survey, 84.5% were from the patient group and 15.5% from the professional group; in round 2 (228 participants), 74.3% were from the patient group and 25.7% from the professional group. 29 items met the criteria for consensus discussion. The final CIS includes 19 information points addressing: labour process, pain relief, labour complications, procedures or interventions during labour, experiences after birth, outcomes for the baby and labour environment.
Conclusions
This CIS can facilitate discussions and support informed decision‐making about vaginal birth
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