Pharmaceuticals

In some countries, melatonin is sold without a physician prescription and dosage is unregulated. Transdermal products have become popular including those marketed for children. We measured consumer assumptions about these products among adult residents of the United States, analyzed lot-to-lot variability, and compared the pharmacokinetics of melatonin administered in oral, lotion, and bath product forms. Survey respondents (n=199) believed oral melatonin was more effective than transdermal products and that all melatonin products were relatively safe. Melatonin lotion products analyzed by HPLC displayed lot-to-lot variability as well as changes in formulation and product claims. To determine pharmacokinetics, three different treatments (oral tablets, lotion, and bath immersion) were administered to twelve undergraduate participants in a randomized, crossover design. Five additional participants completed bath product treatment only. Participants collected saliva samples up to 48 hours after administration, which were analyzed for melatonin by enzyme-linked immunosorbent assay. Oral (n=11) and lotion formulations (n=12) caused maximum salivary melatonin levels within 30 minutes after administration, but bath immersion did not cause increases in saliva melatonin (n=17). The half-life of oral melatonin was 1.17 [0.69 -- 1.65] hours versus 5.72 [3.75 -- 7.68] hours for lotion treatment (p = 0.011, effect size r = 0.770). Melatonin lotion may pose a risk to consumers who assume it is safe and less effective than oral tablets, when in fact it may be very potent and remain at high physiological levels into the following day. This study is registered on clinicaltrials.gov (NCT06382610) and was funded by the Sleep Research Society.

Background: Platinum-based chemotherapy is known to cause severe and debilitating hearing loss, but unlike cisplatin, the true incidence of carboplatin-induced hearing loss remains unclear. We evaluated functional hearing outcomes in children receiving carboplatin to determine the incidence and severity of ototoxicity. Procedure: We identified a large cohort of children with cancer treated with carboplatin and graded their audiograms using the SIOP ototoxicity scale. Patients with inadequate audiological follow-up, prior hearing loss, or exposure to cisplatin were excluded. Fishers exact test, logistic regression, and ROC analyses were performed to investigate associations of demographic, treatment, and exposure-related risk factors with incidence of hearing loss. Results: 200 patients were included, all of whom had been treated with carboplatin. Only nine (4.5%) patients developed clinically significant hearing loss (SIOP grade [≥]2). Younger age at first exposure to carboplatin was the only significant predictor of hearing loss (OR = 0.7888, p=0.0241). Age [≤]28 months was significantly associated with hearing loss (OR 12.37, p=0.0042). No other risk factors or exposures were statistically significant. Conclusions: Clinically significant carboplatin-associated hearing loss was uncommon (incidence 4.5%). We show that young age is the single-most important risk factor for hearing loss; of nine children who developed hearing loss, eight were aged [≤]28 months. Children below this age have twelve-fold higher odds of developing hearing loss compared to those above this age (OR 12.37). These findings will allow physicians to provide more appropriate counselling to families regarding ototoxic risk and support intensified hearing surveillance in young children.

Introduction: Adenoviral vectors such as chimpanzee ChAdOx1 were selected for COVID-19 vaccines due to their low seroprevalence in humans, minimizing the impact of neutralising anti-vector immunity that could attenuate vaccine responses. However, the influence of pre-existing adenoviral immunity on vaccine response remains incompletely understood. We have previously shown that SARS-CoV-2 spike-specific T cells were enhanced in ChAdOx1 nCoV-19 vaccinated immunodeficient patients compared to mRNA-based BNT162b2. Here, we assess immune cross-reactivity between ChAdOx1 and human adenovirus 5 (HuAd5), and test the hypothesis that in antibody-deficient individuals, cross-neutralisation may be impaired, allowing bystander enhancement of SARS-CoV-2 spike-specific T cell responses following ChAdOx1 nCoV-19 vaccination. Methods: We studied healthy healthcare workers (HCWs) and immunodeficient patients (IDPs) who received homologous ChAdOx1 nCoV-19 or BNT162b2 vaccines. HCWs samples were collected pre-vaccination and 4-6 weeks after the second dose, while IDP samples were obtained 4-6 weeks after the second dose. Serum anti-HuAd5 hexon IgG was quantified using a Luminex multiplex assay, and neutralizing antibodies were assessed using a replication-deficient HuAd5-GFP virus neutralization assay with flow cytometry readout. Ex vivo ELISpot and flow cytometry assays were used to measure T cell responses to HuAd5 hexon. These data were compared with previously published ChAdOx1 nCoV-19 vaccine responses in the same cohorts. Results: HuAd5 hexon-binding IgG titres were significantly higher in ChAdOx1 nCoV-19 compared to BNT162b2 vaccine recipients in both HCWs (p = 0.0043) and IDPs (p = 0.0328). Within ChAdOx1 nCoV-19 vaccine group, titres were lower in IDPs than HCWs (p = 0.0015) but not within the BNT162b2 group (p = 0.1261). HuAd5 neutralisation titres did not differ between cohorts or vaccine groups. In ChAdOx1 nCoV-19 vaccinated IDPs and HCWs, there was a significant negative correlation between HuAd5 hexon IgG titres and SARS-CoV-2 spike-specific T cell responses. Similarly, HuAd5 neutralisation titres showed an inverse correlation with spike-specific T cell responses in ChAdOx1 nCoV-19 vaccinated IDPs and HCWs. ChAdOx1 nCoV-19 vaccination induced significantly higher frequencies of HuAd5 hexon-reactive T cells compared with BNT162b2 vaccination in IDPs (p < 0.0001), consistent with cross-reactive adenoviral T cell responses. In IDPs, HuAd5 hexon-specific T cell frequencies positively correlated with SARS-CoV-2 spike-specific T cell responses following ChAdOx1 nCoV-19 vaccination but not following BNT162b2 vaccination. Functional profiling in ChAdOx1 nCoV-19 vaccinated IDPs demonstrated expansion of HuAd5 hexon-specific CD4IFN-{gamma}TNF T cells in high SARS-CoV-2 spike responders (p = 0.0002) compared to low responders, and the frequency of these cells strongly correlated with spike-specific T cell response. Discussion: ChAdOx1 nCoV-19 has been associated with stronger T cell responses than BNT162b2 in certain populations, including immunodeficient and elderly individuals. While this has been attributed to antigen persistence and innate adjuvant effects, our findings support a mechanism whereby heterologous pre-existing adenovirus immunity modulates vaccine-induced responses. Specifically, cross-reactive HuAd5-specific T cells may enhance spike-specific T cell responses via bystander enhancement, while cross-reactive binding antibodies may exert opposing effects. An implication of this study is that vaccine protocols could incorporate therapies that suppress vector-specific or cross-reactive antibodies while preserving T cell responses especially in cases where T cell-specific responses are most desirable. Also, safe vector-based vaccines can be developed for patient groups with predominant antibody deficiency. Targeted vaccination strategy could be implemented for clinical cohorts based on immune competence.

Background As lockdown measures was eased, pregnant women faced an elevated risk of COVID-19 infection, potentially impacting their mental health. This study aimed to investigate the prevalence of antenatal depression (AD) post-lockdown and develop predictive models for AD risk using machine learning. Methods A cross-sectional study utilizing the Edinburgh Postnatal Depression Scale was conducted in Beijing and Guizhou, China, from January to August 2023. Data was randomly split into training and test datasets (6:4 ratio), with logistic regression (LR), Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Random Forest (RF), eXtreme Gradient Boosting (XGBoost), and Gradient Boosting Decision Tree (GBDT) models trained and compared. The best model underwent further examination, including SHapley Additive exPlanations (SHAP) for feature importance, calibration curve (CC) for discrimination, and decision curve analysis (DCA) for clinical benefit. Results The effective response rate was 91.07% (459/504), with 25.7% (118/459) testing positive for AD. Multivariate analysis identified "sleep disorders," "family support level," and "COVID-19 symptom severity" as independent predictors. RF model showed the highest area under the curve in both training (0.842) and testing (0.724) datasets, with SHAP emphasizing the greatest impact of "sleep disorders" on AD. The RF model's calibration (P > 0.05) and clinical utility across thresholds (8%-95% and 10%-58%) were confirmed by CC and DCA, respectively. Conclusions AD strongly correlated with "sleep disorders," "family support level," and "COVID-19 symptom severity" post-lockdown, and the EPDS-based RF model effectively predicted AD risk.

Background: Antimicrobial resistance is the world's silent pandemic. The public knowledge, attitudes, and practices (KAP) about antibiotic usage are strongly related to the growing problem in Nepal. Methods: A cross-sectional descriptive survey was done to 263 respondents. Information on KAP regarding antibiotics, primary healthcare sources, and demography was collected through a questionnaire. To identify health literacy gaps and characteristics that contribute to improper antibiotic use, this study assessed these variables across an age group from 18 to 60 years. Descriptive statistics analysis was performed to analyze the data. Results: The majority of respondents were between the ages of 18 and 39 (85.1%), female (63.1%), and had at least a bachelor's degree (67.8%). Significant misunderstandings about antibiotics remained, even though 77.6% of respondents correctly recognized antibiotics as effective against bacteria; 44.1% incorrectly believed that antibiotics cure viral diseases, and 87.8% felt that antibiotics should be stopped right away if adverse effects develop. In practice, 52.9% acknowledged quitting antibiotics as soon as symptoms improved, despite 89.4% consulting doctors. Additionally, 43% of respondents said they have taken antibiotics without a prescription, frequently due to pharmacist recommendations (21.67%) and financial or geographical constraints. The main sources of information were doctors (11.07%) and pharmacist-doctor combinations (14.88%), yet 81.8% of respondents said they had never heard of the phrase antimicrobial resistance. Conclusion: There is a significant lack between theoretical understanding and practical application, despite the high levels of fundamental knowledge toward the prohibition of non-prescription sales. Self-medication and early withdrawal are still common inappropriate practices. It is crucial to implement focused teaching initiatives that highlight the differences between bacterial and viral diseases as well as the risks associated with leftover medicine. It is advised to use digital platforms for younger demographics and to strengthen the role of pharmacists in order to reduce AMR.

Background School stress and psychosomatic complaints are linked and increase in high-income countries, with differences between countries. Evidence of how these parameters develop in Italy, particularly through combined parental and self-reported perspectives across age and gender, is limited. Methods A population-based online survey investigated school stress and psychosomatic complaints in children and adolescents aged 6-19 years, analyzing proxy- and self-reported data based on standardized validated instruments. Data was stratified by gender and age for children (6-10), early adolescents (11-14), and late adolescents (15-19). Results For early and late adolescents, the gender gap was evident, with higher levels of stress and health complaints in late adolescent girls. In this group, 56% of the girls self-reported rather/high school stress, and 43% of the boys. Parents perceived school stress and psychosomatic problems of their children as less severe than adolescents themselves. Parents stated a higher effect of parental help with school problems, and a lower effect of physical activity and digital media use on their childrens psychosomatic problems. Physical activity was related to fewer psychosomatic complaints, especially in girls. Conclusions This study identified late adolescent girls as vulnerable group, underscoring the critical need for gender-specific early prevention strategies starting in childhood, particularly for families with lower socioeconomic status. Parental perspectives may underestimate adolescents stress levels and psychosomatic well-being. In early adolescence, less digital media use may prevent psychosomatic problems, in late adolescence, physical activity may be a preventive method. Further longitudinal investigations should put a special focus on self- and proxy-reported perspectives.

Background Outpatient groin hernia repair is widely recommended globally due to clinical and socioeconomic efficiency, yet it remains underutilized in developing healthcare systems like Tunisia. This study aimed to evaluate the feasibility of a newly implemented day-surgery clinical pathway for groin hernias and identify specific predictors associated with outpatient discharge failure. Methods A prospective, observational cohort study was conducted at a Tunisian tertiary hospital between September 2023 and April 2024. A total of 85 consecutive patients scheduled for elective groin hernia repair under an optimized clinical pathway were enrolled. Inclusion criteria spanned ASA classes I-III, age [&ge;]16 years, proximity to the hospital [&le;]50 km), and presence of a literate adult caregiver. Outpatient failure (unanticipated admission) was defined as the inability to achieve discharge within 24 hours post-surgery. Statistical associations were determined using Chi-squared, Fisher's exact, and independent t-tests. Results The cohort primarily comprised males (n = 82, 96.5%) with a mean age of 56 years (range: 19-86). Successful ambulatory discharge was achieved in 80 patients (94.1%), yielding a failure rate of 5.9% (n = 5). Unanticipated admissions were triggered by uncontrolled pain (n = 1), acute anxiety (n = 2), decompensation of comorbidities (n = 1), and a Post-Anesthetic Discharge Scoring System (PADSS) score < 10 (n = 1). Overall 30-day morbidity was low (2.4%), presenting as minor wound or scrotal hematomas managed conservatively; no surgical site infections, acute urinary retention, or mortality occurred. Univariate analysis revealed that a hernial sac size measured at its maximum diameter between 1.5 and 3 cm was significantly associated with ambulatory failure (p = 0.047). General anesthesia showed a trend toward increased failure compared to regional anesthesia (p = 0.08). Conclusion Day-surgery groin hernia repair is highly safe and feasible in resource-constrained environments, even for elderly or stable ASA III patients, provided rigorous social criteria are satisfied. A small hernial sac size (1.5-3 cm) constitutes a major anatomical predictor of failure, likely due to distinct dissection dynamics and localized post-operative pain profiles.

Abstract Background: Mean platelet volume (MPV) is a simple, low-cost biomarker that reflects platelet activation. Its prognostic value in septic shock remains controversial. We aimed to determine whether MPV at intensive care unit (ICU) admission is associated with hospital mortality in patients with septic shock. Methods: Retrospective cohort study of consecutive adults with septic shock (Sepsis-3 criteria) admitted to a single ICU. MPV, severity scores (SOFA, APACHE II, SAPS II), procalcitonin, and clinical data were collected. The primary outcome was in-hospital mortality. Spearman correlation, univariate and multivariate logistic regression (with Firth's correction), ROC curves, and subgroup analyses were performed. Results: Fifty-eight patients were included; mortality was 58.6%. MPV did not differ between non-survivors and survivors (13.09 {+/-} 1.37 vs. 12.66 {+/-} 1.45 fL, p = 0.259). MPV showed a weak correlation with procalcitonin ({rho} = 0.394, p = 0.002) but not with severity scores. In multivariate analysis adjusting for age, sex, SOFA and comorbidity count, MPV was not an independent predictor of mortality (OR 1.075, 95% CI 0.682-1.755, p = 0.749). The area under the ROC curve for MPV was 0.598 (95% CI 0.444-0.752), significantly lower than that of SOFA (0.837) and procalcitonin (0.836). Subgroup analyses showed no significant association between MPV and mortality in any stratum. Conclusions: In this cohort of septic shock patients, MPV at ICU admission was not associated with hospital mortality and had poor discriminative ability. Widely used severity scores and procalcitonin remain superior prognostic markers. MPV should not be used as a prognostic tool in septic shock. Keywords: Septic shock, Mean platelet volume, Mortality, SOFA, Procalcitonin, Biomarker

Background/Objectives People living with HIV face overlapping hardship through medical, behavioral, and social needs that require an integrated and coordinated approach. Harlem United multiservice model provides healthcare, food assistance, housing support, harm reduction services, behavioral health counseling, case management, and much more to support their clients. This study is an examination on how the participation in the Harlem United multiservice model is associated with changes over time in client health, behavioral health, and social outcomes. Methods This study performed a longitudinal program evaluation examining Harlem United clients enrolled between January 2020 and January 2025 who remained engaged in services for a minimum of one year. Client outcomes were assessed across three time points: Baseline, Year 1, and Year 2. The sample included 154 clients at baseline (N=154) with a total of 428 observations (N=428). Quantitative measures that were assessed included program involvement, housing stability, PHQ4 scores, food insecurity, medication adherence, and viral suppression. Data was analyzed using IBM SPSS Statistics through descriptive statistics, frequency tables, and generalized estimating equation models (GEE) to account for repeated observation over time. Results Medication adherence and viral suppression remained consistently high across all time points in the longitudinal study suggesting that most clients were virally suppressed or undetectable at baseline. Housing stability was statistically significant Wald X2 (2) = 156.073, p < 0.001 with improvements noted in Year 1 and Year 2 compared to baseline. Program level was significantly associated with PHQ4 scores, Wald X2 (1) = 7.902, p = 0.005. Food insecurity was also associated with PHQ4 scores, Wald X2 (1) = 5.462, p = 0.019. Findings suggest that clients with higher PHQ4 scores were involved in more programs compared to clients only enrolled in 1-2 programs. Additionally, clients with higher PHQ4 scores were more food insecure highlighting the relationship between social needs and mental health. Conclusion: Findings suggest that the Harlem United multiservice model played a supportive role in the maintenance of health and social outcomes through medication adherence and viral suppression. Although, significant improvement was not reflected across several outcomes, the association between PHQ4 scores, food insecurity, and an increase in program involvement suggest that the multiservice is reaching more clients with complex behavioral and social needs. Continued integration of these services is important for sustaining client stability while addressing social determinants of health.

Objective To examine the effects of combined oral contraceptive (OC) use on clinical markers of ovarian reserve by comparing Anti-Muellerian Hormone (AMH), antral follicle count (AFC), and ovarian volume (OV) before and after starting or stopping OC. Methods This analysis is based on data from a prospective cohort study conducted at the University Hospital Tubingen, Germany, as part of the IRTG-2804 project. A total of 54 healthy women were included and categorized into three groups based on their OC use status: OC starters (n = 12), stoppers (n = 16), and long-term OC-users (n = 26). Each participant underwent a transvaginal ultrasound (including AFC and OV) and serum sampling (including AMH) at two time points (S1 and S2), three to six months apart. OC starters were assessed first during the early follicular phase (day 1-7) and then during active OC intake (day 8-21), while stoppers were assessed in the reverse order. Long-term users were assessed twice during active OC intake. Results OC stoppers showed significant within-group increases in all ovarian reserve markers, including AMH ({Delta} = 2.57 ng/mL, p < .001), AFC ({Delta} = 3.88, p = .004), and OV, which almost doubled (1.94-fold increase; 95% CI [1.35, 2.80], p < .001). In contrast, OC starters exhibited a significant decline in AMH ({Delta} = -1.25 ng/mL, p = .013), but no changes in AFC or OV. No significant longitudinal changes were observed among long-term OC users. Conclusion AMH levels decrease after starting OC use whereas AFC and OV are not affected. In contrast, AMH, AFC, and OV recover within three to six months after stopping OC, suggesting a reversible suppression of ovarian reserve markers during OC use. These findings are clinically relevant for fertility counseling and for the interpretation of ovarian reserve markers in women using hormonal contraception.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease associated with impaired mucociliary clearance and persistent inflammation. While prior work has focused on inflammatory and molecular pathways, the physicochemical properties of mucus itself remain poorly characterized. This study aimed to define compositional and biophysical features of CRS mucus that may contribute to dysfunction. Methods: A prospective cross-sectional study was conducted in 15 adults undergoing endoscopic sinus surgery (11 CRS, 4 controls). Mucus was collected from the middle meatus. Hydration was measured by lyophilization. Ionic composition was quantified using mass spectrometry. Viscoelasticity was assessed via oscillatory shear rheology. Total protein, total carbohydrate, sialic acid (Sia) and fucose (Fuc) content were quantified using enzymatic and chemical assays. Statistical comparisons were performed using nonparametric tests. Results: CRS mucus exhibited significantly higher Ca2+; and Mg2+; concentrations (approximately two-fold; p<0.05) and increased variability in hydration and ion content compared to controls. Rheology showed greater heterogeneity and a non-significant trend toward increased viscoelasticity in CRS. Total protein and carbohydrate content were not significantly different; however, the carbohydrate-to-protein ratio was significantly reduced in CRS (p=0.04). Sia content and Sia-to-carbohydrate ratio were significantly elevated in CRS (p=0.04 and p=0.002), particularly in CRS with nasal polyps. Fuc content did not differ between groups. Conclusions: CRS mucus demonstrates coordinated alterations in ionic composition and glycosylation, characterized by increased cation content, hypersialylation, and reduced carbohydrate-to-protein ratios. These changes may contribute to altered mucus properties and impaired mucociliary clearance, highlighting mucus composition as a potential therapeutic target in CRS.

Abstract Background: Schools are widely recognised as key settings for promoting childrens health behaviours. However, many schools struggle with the implementation and especially sustainment of health promotion programmes e.g. due to limited resources. Strengthening schools capacity for health promotion has therefore been identified as a central strategy for achieving better implementation and ultimately behaviour change outcomes among children. The fit4future Kids programme was developed as a large-scale, multi-component initiative in Germany that aims to promote childrens physical activity, nutrition, mental health, and responsible digital media use while simultaneously supporting schools in building structures for sustainable health promotion. Methods: This paper describes the intervention and evaluation protocol of the nationwide fit4future Kids programme implemented in several cohorts of German primary schools from Sept. 2022 to Sept. 2027. The intervention is based on the Health Promoting Schools framework and integrates established implementation and behaviour change frameworks, including the Consolidated Framework for Implementation Research, the COM-B model, and Behaviour Change Techniques. The programme combines curricular materials, environmental components, and structured implementation support to facilitate the integration of health promotion into everyday school practice. The evaluation follows a mixed-methods design involving multiple stakeholder groups, including school staff, parents, and children. Quantitative and qualitative data are collected to assess implementation processes, contextual factors, and programme outcomes. The large and diverse sample of 1,153 participating primary schools allows for the exploration of different implementation trajectories and the investigation of potential equity-related effects. Discussion: By combining evidence-based health promotion strategies with implementation science approaches, fit4future Kids provides a large-scale real-world example of how schools can be supported in implementing sustainable health promotion. The evaluation is expected to generate important insights into the implementation and potential effectiveness of multi-component school-based interventions and to inform future initiatives aiming to strengthen health-promoting school environments.

Background: Psychedelics are emerging as potential management options for chronic musculoskeletal pain due to preliminary evidence of effectiveness and low addictive potential, but patients perceptions remain unknown. This study assessed patient perceptions regarding psilocybin for musculoskeletal pain. Methods: We conducted a cross-sectional survey of adults ([&ge;]19) with musculoskeletal pain attending a hospital-based orthopaedic clinic. Participants reported demographics, perceptions of psychedelics for pain management, and willingness to participate in psychedelic research. Multivariable regression explored factors associated with perceived analgesic potential, and willingness to try a full therapeutic dose of psilocybin or a microdose. Results: Among 295 participants, 73% reported moderate-to-severe pain; 75% used analgesics; of these, 41% used opioids (86/209). While 24% reported prior psychedelic use, only 3% had discussed psychedelics with a healthcare provider. Most perceived that psilocybin had moderate-to-high effectiveness for pain (76%). Most respondents endorsed a moderate-to-high willingness to try microdoses (58%) and macrodoses (53%) of psilocybin for pain. Prior non-therapeutic psychedelic use predicted a 1.05-unit increase in perceived analgesic potential on the 10-point scale (p=.013). Willingness to try a macrodose of psilocybin was most strongly associated with prior non-therapeutic (B=3.16) and therapeutic (B=2.42) psychedelic use; in contrast, pain severity had a significant but modest association, with a 0.21-point increase in willingness for every 1-unit increase in pain severity (p=.017). Similarly, willingness to try a microdose of psilocybin was predicted by non-therapeutic (B=2.82) and therapeutic (B=2.48) use, whereas the effects of pain severity (B=0.20) and younger age (B=-0.30) were significant but small. Most respondents (52%) reported moderate-to-high willingness to participate in a trial of psilocybin for pain relief, and health risks were the primary concern (33%). Conclusions: Study findings suggest a majority hold neutral-to-positive perceptions of psilocybin for pain. Addressing perceived barriers, including health effects and gaps in patient knowledge, should be considered when designing future trials.

Abstract Aims To examine which demographic groups nicotine pouch advertisers chose to target on social media, and which groups Meta's algorithms actually delivered the adverts to. Design Cross-sectional analysis of advert-level data from the Meta Ad Library. Setting Meta social media platforms (including Facebook and Instagram) in the UK. Cases A random sample of 741 nicotine pouch adverts shown in the 12 months up to December 2025, and a comparison sample of 1,125 general adverts. Analyses of reach were restricted to adverts eligible for all genders and adult ages (444 pouch adverts; 674 general). Measurements Outcomes were advertiser-set gender and age-group targeting criteria (i.e., groups eligible to be shown each advert) and estimated advert reach to each group (i.e., number of people who saw each advert). Male-to-female reach ratios within age groups, and reach ratios comparing age groups, were calculated per advert and summarised using geometric means. To assess whether patterns were pouch-specific, comparisons with general adverts were made using ratios of reach ratios (RRR). Findings Advertisers of nicotine pouches targeted a broad sample; most adverts (79.1%; 586/741) were eligible to be shown to all genders, the remainder were restricted to men only. All were restricted to adults (minimum age 18 years) and most (95.6%; 708/741) had no upper age limit. Despite this, of pouch adverts eligible to be shown to all adults, adverts were more likely to reach men, particularly among younger men. Among 18-24-year-olds, pouch adverts reached around ten times as many men as women (RR 10.0, 95% CI 8.7-11.5), compared with a slight skew towards women for general adverts (RR 0.81, 95% CI 0.71-0.94), corresponding to an RRR of 12.3 (95% CI 10.0-15.1). Pouch adverts also showed a skew in reach towards younger age groups. Relative to those aged 35-44 years, reach was higher among 18-24-year-olds for nicotine pouch adverts (RR 1.33, 95% CI 1.17-1.51) but much lower for general adverts (RR 0.19, 95% CI 0.17-0.21), corresponding to an RRR of 7.0 (95% CI 6.0-8.2). Conclusions Nicotine pouch adverts on social media are often eligible to be shown broadly to all demographic groups but are disproportionately delivered to young men.

Introduction Aquablation for surgical treatment of benign prostatic enlargement (BPE) causing bladder outflow obstruction (BOO) has demonstrated good functional outcomes, even for large glands, with high rates of ejaculatory preservation reported. This is a protocol for a study that aims to review real-world outcomes of ejaculatory preservation or restoration post-Aquablation in an unselected cohort and compare to published clinical trial outcomes. Methods Retrospective data will be collected from a prospectively maintained consecutive case series of patients who underwent Aquablation, in a single UK centre. The primary outcome is ejaculatory function subjectively reported by men post-operatively, and classified as: antegrade ejaculation, retrograde/low volume ejaculation, anejaculation or not sexually active. Secondary outcomes are International Prostate Symptom Severity (IPSS), Quality of Life (QoL) Score, post-void residual (PVR), and incontinence. Descriptive and comparative statistical tests will be performed. Conclusions This study will review real-world ejaculatory function and clinical outcomes following robotic Aquablation for prostatic bladder outflow obstruction and compare this to published clinical trial outcomes.

ABSTRACT Background: Self medication with analgesics and non steroidal anti inflammatory drugs (NSAIDs) is common in low- and middle income countries and may expose users to preventable adverse outcomes. Evidence from Guinea remains scarce. This study aimed to estimate the prevalence of self medication with analgesics and NSAIDs among pharmacy clients in urban Conakry, identify associated factors, and describe clinical risk situations. Methods: We conducted a pharmacy based analytical cross sectional study in 30 private pharmacies across Conakry, Guinea. A total of 1,032 participants seeking analgesics or NSAIDs were enrolled between November 3, 2012, and April 5, 2013. Self-medication was defined as acquisition or use without a valid medical prescription. Factors associated with self-medication were analysed using multivariable logistic regression. Results: Among 1,032 participants, 603 reported self medication (prevalence 58.4%). Previous unsupervised use was reported by 78.7%. The most frequently used medicines were paracetamol (56.9%, n=587), diclofenac (21.3%, n=220), ibuprofen (17.9%, n=185), and aspirin (3.9%, n=40). Overall, 68.0% (n=702) reported no knowledge of potential adverse effects. Clinical risk situations were frequent: gastrointestinal disorders (41.3%, n=426), hypertension (9.2%, n=95), and pregnancy exposure among reproductive age women (26.0%). In multivariable analysis, self medication was independently associated with previous analgesic/NSAID use (aOR = 2.8, 95% CI: 2.1 to 3.6), lack of knowledge of adverse effects (aOR = 1.9, 95% CI: 1.4 to 2.5), informal occupation (aOR = 1.6, 95% CI: 1.2 to 2.2), and age 18 to 59 years (aOR = 1.5, 95% CI: 1.1 to 2.1). Conclusions: In this pharmacy based study conducted in urban Conakry, self medication with analgesics and NSAIDs was common and frequently associated with limited awareness of potential adverse effects. These findings support the need for strengthened pharmaceutical regulation, pharmacist-led counselling, health literacy interventions, and improved access to primary care. Keywords: self medication; analgesics; NSAIDs; paracetamol; diclofenac; ibuprofen; pharmacy; Guinea; Conakry; drug safety; public health.

Background: Sexual and gender minorities (SGM), including men who have sex with men (MSM) and transgender women, often face stigma, legal constraints, and limited access to sexual and reproductive health services. These conditions restrict prevention and care, increasing vulnerability to HIV and human papillomavirus (HPV) infections. While strong HIV-HPV interaction is documented in high-income settings, evidence from low- and middle-income countries remains limited. This study examines the burden, co-infection dynamics, and progression of HPV infection and anal dysplasia among MSM and transgender women in Pakistan. Methods: A cross-sectional study was conducted between September 2015 and October 2016 among men who have sex with men (MSM) and transgender women recruited from sexual health and antiretroviral therapy centers in Karachi. Eligible participants were aged [&ge;]18 years and self-reported anal sex within the past 6 months (N=298). Two anal specimens were collected for HPV DNA detection and genotyping using PCR, and anal squamous intraepithelial lesions (ASIL) were assessed cytologically using the Bethesda classification. Associations were estimated using Cox proportional hazards regression algorithms to derive prevalence ratios (PRs). Results: Among participants, 44% (n=133) were living with HIV. Overall HPV prevalence was 65.1%, rising to 87% among HIV-positive individuals compared to 48% among those without HIV ({chi}{superscript 2}p[&le;]0.001). Likewise 28.9% of participants living with HIV were infected with two or more than two types of HPV as compared with 18.8% participants without HIV ({chi}{superscript 2}p[&le;]0.001). HIV infection was strongly associated with HPV acquisition (adjusted PR 2.81, 95% CI 2.16-3.82). Among HPV-positive participants (n=194), 58.8% were co-infected with HIV. High-risk HPV was highly prevalent among those living with HIV (83.2% vs. 35.3% ({chi}{superscript 2}p[&le;]0.001)), with HPV16 as the dominant oncogenic type. Multiple HPV infections were more common among HIV-positive individuals ({chi}{superscript 2}p[&le;]0.001), and HIV seropositivity was 3.43 (95% CI: 2.55-3.51) times higher among those with high-risk HPV. Co-infected participants demonstrated prolonged smoking, longer duration of sex work, high-intensity sex work with limited condom negotiation, and higher prevalence of anal warts (all p<0.05). Anal dysplasia (ASIL) was present in 35% of participants and was higher among HIV-positive individuals (42.4% vs. 28.1%, p<0.001). HIV-HPV co-infection was independently associated with ASIL (adjusted PR 1.75, 95% CI 1.07-2.88), while high-risk HPV further amplified this risk (PR 3.04, 95% CI 1.75-5.26). Conclusion: These findings demonstrate a biological continuum in HIV-positive MSM and transgender women, where HIV increases HPV acquisition, persistence, and multiplicity, accelerating progression to anal dysplasia. This reflects a syndemic shaped by biological interaction and structural vulnerability. Integrating HPV screening and vaccination within HIV services is essential to interrupt progression to cancer in this high-risk population.

Introduction: Managing gestational weight gain (GWG) is crucial for the health of mothers and their children. Mobile applications (apps) specifically designed for pregnancy are emerging as modalities to deliver accessible lifestyle intervention at a low-cost. However, current studies are varied in results and suffer from heterogeneity. Thus, we conducted this systematic review and meta-analysis to summarize the efficacy of mobile apps in managing GWG and investigate variables that may contribute to heterogeneity. Methodology: Seven databases were systematically searched up to 9 November, 2024. Only randomized controlled trials (RCTs) were included. Outcomes were excessive GWG and inadequate GWG according to the 2009 Institute of Medicine (IOM) guideline. Quality appraisal was performed using the Cochrane Risk of Bias 2 (RoB 2) tool. Random-effect model meta-analysis was conducted using odds ratio (OR) as the summary measure alongside their 95% confidence intervals (CI). Results and Discussion: Fifteen RCTs were included. Mobile apps led to a significant overall decrease in excessive GWG (OR: 0.71; 95% CI: 0.54 to 0.95; p-value: 0.02; I2: 60%). Subgroup analysis showed that social media apps, self-monitoring functionalities, and overweight/obese patients are associated with a significant reduction in excessive GWG. However, there was significant evidence of small-study bias in the analysis. Moreover, mobile apps also significantly increased inadequate GWG (OR: 1.51; 95% CI: 1.04 to 2.21; I2: 0%). Meta-regression did not reveal any significant finding. Conclusion: In conclusion, mobile app interventions are shown to be effective in preventing excessive GWG, particularly social media apps and those with self-monitoring functionalities. However, the reduction in excessive GWG may only be seen in overweight and obese patients and more studies are needed to ascertain this finding. Lastly, mobile apps are associated with an increased risk of inadequate GWG and strategies to combat inadequate GWG are needed.

Introduction: Menstrual cycle phase has been proposed as a source of intra-individual variability in resting energy expenditure and the thermic effect of food in premenopausal females, yet studies examining the thermic effect of food across menstrual cycle phases report conflicting findings. Methods: This protocol describes a secondary analysis of prespecified outcomes from a non-randomized, two-period crossover trial primarily designed to assess postprandial plasma triglyceride concentrations across menstrual cycle phases (ClinicalTrials.gov: NCT07459465) in 12 premenopausal females aged 18-30 years, free of chronic disease and hormonal contraceptive use, recruited in Ottawa, Canada. Participants complete two experimental sessions: one in the early follicular phase and one in the mid-luteal phase, each involving consumption of a high-fat meal. Eleven secondary outcomes will be reported: fasting resting energy expenditure, thermic effect of food, respiratory exchange ratio, carbohydrate oxidation rate, lipid oxidation rate, desire to eat, hunger, fullness, prospective food consumption, serum beta-estradiol, and serum progesterone. Masked outcome analyses are performed using linear mixed-effects models. Results: Recruitment began on 26 March 2026; results will be reported in the Stage 2 manuscript. Discussion: Findings from this trial may help clarify whether menstrual cycle phase constitutes a meaningful source of intra-individual variability in energy metabolism, with implications for the design of metabolic research in premenopausal females.

Background: Rheumatoid arthritis is a chronic inflammatory disorder in which exercise is increasingly recognized as an important component of long-term management. Yet, most reviews in this field evaluate the effects of single exercise modalities, while bibliometric studies primarily identify publication trends and research hotspots without showing whether highly visible themes also represent coherent and comparatively mature evidence domains. Methods: We searched the Web of Science Core Collection for publications on exercise interventions in rheumatoid arthritis from 2016 to 2025. CiteSpace (6.4.1) and VOSviewer (1.6.20) were used to analyze publication growth, collaboration networks, keyword co-occurrence, thematic clusters, and burst terms. We then applied structured content coding in Excel 2021 to classify exercise modalities, outcome domains, and mechanistic topics, and integrated these findings into a visual evidence-distribution profile. Results: Publication output increased from 16 studies in 2016 to 37 in 2025. The United States led in productivity, Karolinska Institutet was the most prolific institution, and Kitas, Duda, and Metsios were among the most influential authors. Keyword analyses identified a shift from function- and disease-focused themes toward quality of life, risk factors, and comprehensive management. The integrated analysis revealed an uneven evidence structure: aerobic and resistance training accounted for the most concentrated and recurrently studied exercise-outcome domains, whereas mind-body and water-based interventions formed visible but methodologically heterogeneous clusters. Newer modalities, including blood flow restriction training and high-intensity interval training, showed growing prominence but limited depth of evidence. Conclusion:Exercise research in rheumatoid arthritis has evolved toward broader and more patient-centered management targets, but the field remains imbalanced across intervention types and outcome domains. This study demonstrates the value of combining bibliometric mapping with structured content analysis to distinguish thematic visibility from evidentiary coherence in heterogeneous intervention fields and may offer a transferable analytical framework for research evaluation beyond rheumatoid arthritis. Keywords: Rheumatoid Arthritis; Exercise Intervention; Bibliometrics; Content Analysis; Rehabilitation