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Purpose: To report a rare case of acute bacterial endophthalmitis that developed after scleral buckling surgery performed with non-contact wide-angle viewing system (WAVS) and chandelier endoillumination., Case Description: A 63-year-old man underwent scleral buckling surgery using a WAVS with chandelier endoillumination for rhegmatogenous retinal detachment repair in his left eye. Seven days after the surgery, the patient noticed a marked decrease in his vision with ocular pain. No anterior chamber inflammation or exudates were found. No focal congestion or exudates were noted at the sclerotomy site. Posterior segment examination revealed severe vitreous haze and yellowish exudates in the vitreous cavity. Ocular ultrasound revealed dense vitritis, complete posterior vitreous separation, a fully attached retina, and a peripheral scleral buckle indent. Vitreous biopsy combined with pars plana vitrectomy with intravitreal antibiotic injections was done immediately, and Staphylococcus epidermidis was detected in the vitreous fluid. Following surgery, the inflammation and infection subsided and the visual acuity recovered to 6/9 in 6 weeks., Conclusion: Infectious endophthalmitis is a rare occurrence after chandelier-assisted scleral buckling (SB) surgery, characterized by ocular pain and a sudden decline in vision as key symptoms. Clinicians should be cognizant of the possibility of its occurrence following SB surgery, especially when utilizing the WAVS with chandelier endoillumination., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To study the outcomes of patients presenting with submacular hemorrhage (SMH) and bacillary layer detachment (BALAD) following intervention., Methods: This retrospective study examined fundus photographs and optical coherence tomography (OCT) scans to identify treatment-naive SMH and BALAD cases. Two groups were formed: SMH cases with and without BALAD. The treatment outcomes of these cases were assessed., Results: Thirteen (65%) of the 20 eyes with SMH had BALAD. Blunt trauma was the most common cause of SMH (n = 10, 50%). Median age was 46 years (IQR range: 28-70). Demographic, clinical, or OCT imaging findings between the groups ( p  > 0.05) were comparable. Nine (45%) patients each underwent intravitreal gas injection alone or along with PPV and TpA injection. At 1-month post-treatment, VA improved (logMAR VA - 0.89; p  = 0.017). BALADs and intrabacillary hemorrhage had resolved in eight (61%) cases. Intraretinal, subretinal, and sub-RPE fluids resolved in 100%, 70%, and 43% of cases, respectively. Eyes with resolved BALAD showed greater improvement in VA (logMAR VA - 0.98) than eyes with persisting BALAD (logMAR VA - 1.1) and resulted in significant decrease in central macular ( p  = 0.016) and retinal thicknesses ( p  = 0.031). SMH eyes without pre-treatment BALAD also observed statistically significant improvement in visual acuity following intervention ( p  = 0.031)., Conclusion: BALAD and intrabacillary hemorrhage in SMH are relatively common. A significant proportion of cases had their BALAD and intrabacillary haemorrhage resolved following treatment. Persistence of BALAD had no effect on VA., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To estimate the number needed to treat and cost per additional responder for atogepant and rimegepant versus placebo for the preventive treatment of episodic migraine (EM) in the United States., Background: Migraine has an enormous impact on a person's daily activities and quality of life, and results in significant clinical and economic burden to both individuals and society. It is important to understand the comparative efficacy and economic value of oral calcitonin gene-related peptide receptor antagonists (gepants) for preventive treatment of EM. Currently, atogepant and rimegepant are US Food and Drug Administration approved for preventive treatment of migraine (rimegepant for EM and atogepant for EM and for chronic migraine). In the absence of head-to-head trials, we utilized an indirect treatment comparison on efficacy data from clinical trials conducted for the preventive treatment of EM. We estimated number needed to treat, a valuable metric used in clinical practice to compare treatment efficacy, and cost per additional responder, which can be used to establish the cost effectiveness of a treatment., Methods: An indirect treatment comparison was conducted to compare the efficacy of atogepant 60 mg once daily and rimegepant 75 mg once every other day as preventive treatments for EM using published data from the registrational trials of atogepant (ADVANCE) and rimegepant (BHV3000-305). The efficacy outcome of interest was ≥50% reduction from baseline in mean monthly migraine/headache days (≥50% responder rate), which was variably defined for a base case and two scenario analyses. Number needed to treat and cost per additional responder versus placebo were calculated and compared between both treatments (weeks 9-12 in the base case analysis; weeks 1-12 and 9-12 for atogepant and during weeks 9-12 for rimegepant in the scenario analyses)., Results: In the base case analysis, ≥50% responder rates were 64.9% (95% confidence interval [CI], 53.9-74.5) for atogepant and 51.8% (95% CI, 42.9-60.6) for rimegepant, compared to 44.1% (95% CI, 39.4-49.0) for placebo. The median number needed to treat versus placebo in the base case scenario was 4.8 (95% CI, 3.1-9.0) for atogepant compared to 13.0 (95% CI, 5.9-75.1) for rimegepant. The cost per additional responder versus placebo in the base case scenario was estimated to be $15,823 (95% CI, $11,079-$29,516) for atogepant compared to $73,029 (95% CI, $32,901-$422,104) for rimegepant. Results of the two scenario analyses were consistent with the base case analysis., Conclusions: Atogepant had substantially lower numbers needed to treat and costs per additional responder versus placebo than rimegepant for the preventive treatment of EM across all evaluated scenarios. These analyses suggest that atogepant may be more cost effective than rimegepant for the preventive treatment of EM. Limitations include differences in inclusion/exclusion criteria and in reporting of the ≥50% responder rates between trials., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Trajectories of mortality after primary prevention implantable cardioverter-defibrillator (ICD) placement for older patients with heart failure during or soon after acute hospitalization have not been assessed., Objective: The purpose of this study was to compare trajectories of mortality after primary prevention ICD placement during or soon after acute cardiac or non-cardiac hospitalization., Methods: We identified older patients with heart failure undergoing primary prevention ICD placement using 20% Medicare data (2008-2018). Placement settings were as follows: (1) Current-H-during current hospitalization, (2) Recent-H-within 90 days of hospitalization, or (3) Chronic stable. Hospitalization was categorized as cardiac vs non-cardiac. Interval mortality rates and hazard ratios (HRs) using Cox regression were estimated at 0-30, 31-90, and 91-365 days after ICD placement., Results: Of the 61,710 patients (mean age 76 years; 35% female; 85% white), 19% (11,947), 25% (15,147), and 56% (34,616) had ICDs in Current-H, Recent-H, and Chronic stable settings. Mortality rates (per 100 person-years) were highest during 0-30 days, with 38 (34-42) and 22 (19-24) for Current-H and Recent-H, which declined to 21 (20-22) and 16 (15-17) during 91-365 days, respectively. Compared to Chronic stable, HRs were highest during 0-30 days post-ICD placement (5.5 [4.5-6.8] for Current-H and 3.4 [2.8-4.2] for Recent-H) and decreased during 91-365 days (2.0 [1.8-2.1] for Current-H and 1.6 [1.5-1.7] for Recent-H). HR pattens were similar for cardiac and non-cardiac hospitalizations., Conclusion: Primary prevention ICD placement during or soon after hospitalization for any reason was associated with worse mortality with diminishing risks after 90 days. Hospitalization likely identifies a sicker population in whom early mortality with or without ICD may be higher. Our results support careful consideration regarding ICD placement during the 90 days after hospitalization., Competing Interests: Disclosures Dr Setoguchi discloses having received research funding from Pfizer Inc, Pfizer Japan, Bristol Myers Squibb, and Daiichi Sankyo and served as a consultant for Pfizer Japan and Merck Co. Inc. All other coauthors have no disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the evolution of posterior staphyloma-induced serous maculopathy (PSISM) in a patient with myopic tilted disc syndrome and its treatment with subthreshold micro pulse laser (SMPL) therapy., Case Description: A 38-year-old male, diagnosed previously with classical features of myopic tilted disc syndrome presented to the retina clinic after 5 years from the initial presentation with blurred vision in the right eye for 6 months, visual acuity of 6/15 and findings of serous macular detachment (SMD) and subretinal precipitates at the upper margin of the posterior staphyloma. Retinal imaging ruled out other causes of SMD such as chronic central serous chorioretinopathy, myopic macular neovascularisation and dome shaped macula. A diagnosis of PSISM was confirmed. The left eye fundus and macula was normal., Results: Confluent SMPL burns were applied across the SMD. The serous maculopathy resolved over a period of 2 months and visual acuity improved to 6/9. No recurrence of SMD was noted even after 14 months post SMPL., Conclusion: PSISM develops gradually in eyes with myopic titled disc syndrome. SMPL is a viable therapeutic option in the management of PSISM and should be considered early in the treatment options., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: Type 2 diabetes (T2DM) manifests as pancreatic disorder as a consequence of low-grade systemic inflammation, attributed to upregulated levels of interleukin-6 (IL-6). This in turn is associated with a reduced incretin effect with lower circulatory GLP-1 levels. Therefore, its important to monitor the circulating IL-6 and GLP-1 levels for better management and outcomes in T2DM patients., Methods: Limited studies being available in literature on circulating concentrations of GLP-1 and IL-6 in T2DM patients, a meta-analysis was conducted by identifying 1558 studies from 3 databases. As per inclusion and exclusion criteria, the studies were screened for the 2-markers.Forest plots were drawn for standardized mean differences and median values were deduced from the datasets. In parallel, analysis was conducted to ascertain the expression levels of the markers by ELISA (n = 52 T2DM patients) in real time., Results: The meta-analysis showed a significant (p < 0.01) standardized mean difference of 3.82 and 1.04 for IL-6 and GLP-1 respectively. The median values obtained from analysis for IL-6 were 26.50 pg/ml which were higher than the controls downregulated levels of GLP-1(8.77 pg/ml) were noted. The above findings are corroborated by the results of our experimental analysis with IL-6 concentrations at 11.603pg/ml and GLP-1 at 13.05pg/ml., Conclusion: The study highlights that systemic concentrations of IL-6 and GLP-1 correspond to a persistent low-grade inflammation and decreased incretin effect in T2DM patients which manifest as pancreatic β-cell dysfunction. The expression of the markers is inversely correlated and monitoring their levels is clinically important for targeting them through their potential antagonists thus reducing the risk of complications, thereby improving the quality of life of the patients., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Purpose: To report a case of punctate inner choroiditis (PIC) and subsequent choroidal neovascular membrane (CNVM) development in a young, high myope following vitreoretinal surgery for rhegmatogenous retinal detachment., Case Description: A 44-year-old male with high myopia underwent pars plana vitrectomy for subtotal retinal detachment in the left eye, followed by cataract extraction and silicone oil removal. Three years postoperatively, he presented with blurred vision, and fundus examination revealed PIC lesions at the posterior pole. Spectral-domain optical coherence tomography (SD-OCT) showed characteristic features of PIC, including hyperreflective nodule-like elevations, disrupted ellipsoid and interdigitation zones, retinal pigment epithelium (RPE) elevations and increased choroidal hyper transmission signals., Results: Initially, no treatment was initiated, and the patient was monitored. Three years later, the patient experienced further vision loss, and fundus examination showed progression of PIC lesions and new CNVM formation in the left eye. The patient was treated with systemic corticosteroids and an intravitreal anti-VEGF injection (Razumab ® 0.5 mg/0.05 ml). Three weeks after the intervention, SD-OCT showed regression of the CNVM, and the patient's visual symptoms improved., Conclusion: This case underscores the importance of long-term follow-up and timely intervention in managing PIC, especially in high myopes post-retinal surgery. Early identification and treatment with systemic corticosteroids and anti-VEGF therapy are crucial to preserving visual function and preventing severe complications like CNVM., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: This study aimed to compare demographics, clinical characteristics, and post-surgical outcomes between idiopathic and secondary full-thickness macular holes (MHs)., Methods: A retrospective analysis of 348 eyes from 339 patients treated between June 2017 and December 2023 was conducted. The study included both idiopathic and secondary MHs, excluding cases where surgery was not performed or lacked sufficient follow-up. Demographic data, visual acuity (VA), ocular characteristics, and optical coherence tomography measurements were analyzed., Results: Idiopathic MHs were identified in 308 eyes (89%), and secondary MHs in 40 eyes (11%). Idiopathic MH patients were older (mean age: 68.26 vs. 60.13 years; p = 0.001) and more commonly female (63% vs. 40%; p = 0.005). Post-surgical closure was achieved in 86% of all MHs, with a median VA improvement of 15 ETDRS letters (3 Snellen lines). However, secondary MHs had a lower closure rate (67% vs. 89%, p = 0.001) and less VA improvement (2 lines vs. 3 lines, p = 0.001) compared to idiopathic MHs. Significant differences in maximal basal diameter and diameter hole index were noted between the groups., Conclusions: Secondary MHs, accounting for 11% of surgical cases, show poorer anatomical and visual outcomes than idiopathic MHs. Despite lower success rates, early surgical intervention in secondary MHs is recommended to enhance outcomes. Differentiating between idiopathic and secondary MHs is crucial for optimal management., (© 2024. The Author(s).)

Aims: Despite advances in therapies, the disease burden of heart failure (HF) has been rising globally. International comparisons of HF management and outcomes may reveal care patterns that improve outcomes. Accordingly, we examined clinical management and patient outcomes in older adults hospitalized for acute HF in the United States (US) and Japan., Methods: We identified patients aged >65 who were hospitalized for HF in 2013 using US Medicare data and the Japanese Registry of Acute Decompensated Heart Failure (JROADHF). We described patient characteristics, management, and healthcare utilization and compared outcomes using multivariable Cox regression during and after HF hospitalization., Results: Among 11 193 Japanese and 120 289 US patients, age and sex distributions were similar, but US patients had higher comorbidity rates. The length of stay was longer in Japan (median 18 vs. 5 days). While Medicare patients had higher use of implantable cardioverter defibrillator or cardiac resynchronization therapy during hospitalization (1.32% vs. 0.6%), Japanese patients were more likely to receive cardiovascular medications at discharge and to undergo cardiac rehabilitation within 3 months of HF admission (31% vs. 1.6%). Physician follow-up within 30 days was higher in Japan (77% vs. 57%). Cardiovascular readmission, cardiovascular mortality and all-cause mortality were 2.1-3.7 times higher in the US patients. The per-day cost of hospitalization was lower in Japan ($516 vs. $1323)., Conclusions: We observed notable differences in the management, outcomes and costs of HF hospitalization between the US and Japan. Large differences in length of hospitalization, cardiac rehabilitation rate and outcomes warrant further research to determine the optimal length of stay and assess the benefits of inpatient cardiac rehabilitation to reduce rehospitalization and mortality., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Histoplasmosis is a systemic infection caused by an endemic dimorphic fungus, Histoplasma capsulatum. Though prevalent in the eastern United States of America, near the Ohio and Mississippi River Valleys, the evidence underlying the global prevalence of histoplasmosis, especially in immunocompromised populations, is underappreciated. This article highlights the global epidemiology, risk factors, microbiology and pathophysiological characteristics, pulmonary and extrapulmonary manifestations, prevention measures, radiographic patterns, diagnostic techniques, and antifungal treatment approaches for Histoplasma capsulatum., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest in relation to the main objectives of this work., (Copyright © 2024. Published by Elsevier Inc.)

Polycystic ovarian syndrome (PCOS) impacts the health of women worldwide. It is a condition consisting of dysfunctional cystic ovaries resulting in hormonal imbalance. Many women have symptoms such as infertility, increased production of androgens, and insulin resistance. Barriers to effective treatment of PCOS include issues such as delays in diagnosis and inconsistencies in treatment plans among physicians. Despite the current use of available medications to decrease symptomatology, women with PCOS continue to report a decreased quality of life. Using the electronic databases PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ScienceDirect, a scoping review was conducted on the globally available treatments for PCOS. After applying pre-determined inclusion criteria, 41 studies were included in this scoping review. The literature on the available treatments for PCOS revealed a wide range of therapeutics with evidence of reduction of symptoms and/or improvement in fertility status and pathological processes such as insulin resistance, hormone imbalance, obesity, inflammation, and infertility. Dozens of treatment options for PCOS have been identified, including new medications and modifications to existing treatment regimens. The hormonal drug Fezolinetant demonstrated effective suppression of hyperandrogenism. Drugs used to treat diabetes, such as Liraglutide, were found effective for weight loss. Green cardamom, cinnamon, and other supplements proved effective in treating metabolic dysfunction. Alternative approaches, such as osteopathic manipulative therapy and acupuncture, decreased sympathetic tone and androgen levels. This review provides a succinct overview of PCOS therapies that can be used by those with PCOS and their physicians everywhere. With a better understanding of their options, women with PCOS can become more involved in the decision-making process to improve their health. More research is needed on novel therapies that aim to reduce the primary pathogenesis of PCOS., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Cochran et al.)

Background and Objectives: Ubrogepant is a calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. The PRODROME trial previously demonstrated that ubrogepant treatment during prodrome prevents the onset of moderate or severe headache. In this analysis of the PRODROME trial, the benefits of ubrogepant treatment during the prodrome on patient-reported outcomes (PROs) are evaluated., Methods: PRODROME was a multicenter, randomized, double-blind, placebo-controlled, crossover trial that enrolled adults who experienced 2-8 migraine attacks per month with moderate-severe headache pain. Eligible participants treated 2 qualifying prodrome events, defined as a migraine attack with prodromal symptoms when the participant was confident a headache would follow within 1-6 hours. Participants were randomized to treatment sequence A (placebo then ubrogepant 100 mg) or sequence B (ubrogepant 100 mg then placebo). This analysis evaluated the ability to function normally over 24 hours (secondary end point) and at specific time points after dose (additional end point). Other PRO end points included activity limitation over 24 hours and satisfaction with study medication at 8 and 24 hours., Results: Of 518 randomized participants, 477 comprised the modified intent-to-treat population. After treatment of qualifying prodrome events, a significantly greater ability to function normally over 24 hours was observed for participants after treatment with ubrogepant 100 mg compared with placebo (odds ratio [OR] 1.66, 95% CI 1.40-1.96; p < 0.0001). As early as 2 hours after dose, a greater proportion of ubrogepant-treated participants reported "no disability, able to function normally" compared with placebo (OR 1.76, 95% CI 1.32-2.35; nominal p = 0.0001). Ubrogepant administered during the prodrome was also associated with a greater reduction in activity limitations over 24 hours after dose (OR 2.07, 95% CI 1.61-2.67; nominal p < 0.0001). At 8 and 24 hours after dose, rates of being "satisfied" or "extremely satisfied" were greater for ubrogepant than for placebo (8 hours: OR 2.37, 95% CI 1.78-3.15; nominal p < 0.0001; 24 hours: OR 2.32, 95% CI 1.78-3.02; nominal p < 0.0001)., Discussion: Ubrogepant 100 mg administered during the prodrome was associated with significantly greater ability to function normally, greater reduction in activity limitations over 24 hours, and greater satisfaction with study medication, compared with placebo., Trial Registration Information: ClinicalTrials.gov NCT04492020. Submitted: July 27, 2020; first patient enrolled: August 21, 2020. clinicaltrials.gov/ct2/show/NCT04492020., Classification of Evidence: This study provides Class II evidence that taking ubrogepant 100 mg during a migraine prodrome allows more patients to function normally over the next 24 hours.

Despite the high prevalence and burden of dysphagia in Parkinson disease (PD), the availability and trustworthiness of clinical practice guidelines (CPGs) regarding its assessment and management remains uncertain. The objective of this study is to appraise the quality of CPGs for dysphagia in PD. We searched OVID Medline, Embase, CINAHL and SpeechBite from January 2011 to July 2023 for guidance documents addressing screening, referral, monitoring, assessment, or management of dysphagia in PD. We additionally conducted an informal search of web pages of relevant professional societies and government organizations. Paired reviewers independently screened studies, and for relevant guidance documents, abstracted data and assessed their quality using the National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards instrument. Thirteen CPGs proved eligible. Of these, eight (62%) were developed by professional societies. Overall, CPGs were deemed low quality. Eleven (85%) CPGs reported funding sources, and nine (69%) reported conflicts of interest. Five (35%) guidance documents included a methodologist, four (30%) included patient partners, four (30%) described study selection processes, and two (15%) clearly described relevant benefits and harms. Regarding dysphagia-specific recommendations, less than half of guidance documents met standards for trustworthiness; six (46%) provided a synthesis of available evidence, eight (54%) specified strength of recommendations, and two (15%) articulated unambiguous recommendations. Limited guidance exists regarding screening, monitoring and referral for dysphagia in PD. Existing guidance frequently fails to meet standards for trustworthiness. International, multidisciplinary, evidence-based practice guidelines with adequate methodological and patient partner involvement are needed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The videofluoroscopic swallowing study (VFSS) is used widely in dysphagia research. However, variations exist in the conduct and interpretation of VFSS, including differences in contrast agents, food and fluid consistencies tested, patient positioning, intervention strategies trialed, fluoroscopy settings, resolution, and image storage solutions. It cannot be assumed that VFSS exams yield directly comparable results across different studies. It is essential that relevant elements of VFSS be clearly reported in research. The goal of this article is to outline optimal VFSS reporting as part of the Framework for RigOr aNd Transparency In REseaRch on Swallowing (FRONTIERS), a critical appraisal tool intended to promote rigor and transparency in dysphagia research., Method: We developed a set of 27 questions regarding the rigor and transparency of VFSS reporting, based on review of previous research articles. These were reviewed by all members of the FRONTIERS Framework collaborative, to determine which questions were mandatory, unnecessary, or needed revision, prior to inclusion in the final critical appraisal tool., Results: The final FRONTIERS Framework tool contains 20 questions and seven subquestions regarding VFSS. These are grouped into four themes: patient/participant positioning, equipment and recording settings, contrast agents, and rating methods, including operational definitions and reliability., Conclusions: The VFSS section of the FRONTIERS Framework tool is intended to facilitate and promote rigorous and transparent reporting of all elements that may influence the interpretation of VFSS in research. This critical appraisal tool can also be used to guide research design and the evaluation of study outcomes contributing to best practices in the field of dysphagia research.

HIV self-testing (HIVST) plays a significant role in addressing the health care needs of high-risk populations, particularly men who have sex with men (MSM). The present systematic review and meta-analysis provide an assessment of the prevalence of HIVST among MSM within the last 5 years. Seven databases (PubMed, Web of Science, Cochrane, Scopus, EMBASE, ProQuest, and EBSCOhost) were searched systematically from January 1, 2018 to March 10, 2023. After an independent search and quality assessment, the pooled prevalence was calculated using a random-effects model. Eight relevant studies were finally included in our study from an initial pool of 288 articles identified through a systematic search. Our meta-analysis revealed that the pooled prevalence of HIVST among MSM is 8% (95% CI: 5%-14%). Significant heterogeneity was noticed among the studies, with an I 2 value of 99% and a 95% prediction interval of 3% to 11%. Geography emerged as a significant moderator of this heterogeneity ( p < .001). Specifically, studies from China reported a notably higher prevalence of 20% (15%-26%), while other countries reported a lower prevalence of 5% (3%-6%). A symmetrical Doi plot with a Luis-Furuya-Kanamori (LFK) index of -0.57 indicated no publication bias. HIVST has a low take-up among MSM globally. Factors leading to variation in HIVST need to be studied. The coordinated efforts of policymakers, health care providers, and affected communities are required in HIVST promotion., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hairy cell leukemia (HCL) makes up 2% of leukemias in the United States and encompasses great molecular heterogeneity. The standard treatment paradigm involves purine nucleoside analogues in the upfront setting with high complete response rate to initial therapy but frequent relapses. There is an increasing role for BRAF inhibitors, with or without rituximab, in refractory and even in untreated patients. The response to purine analogues in HCL variant cases, otherwise classified as splenic lymphoma with prominent nucleolus in the 5th WHO edition classification, is less robust. Several antibodies, small molecular inhibitors, and combination regimens have been explored in HCL but data is frequently limited by case reports or small case series. Here we review available treatment options including their efficacy and safety profiles. We also explore investigational agents and potential future targets. The goal is to present a comprehensive therapeutic review of this rare disease entity and outline the ever increasing and novel therapeutic management options which interrupt key pathways in the pathogenesis of this malignancy., Competing Interests: Disclosure The authors declare they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Mixed dentition analyses are used to determine possible tooth-size and arch-length discrepancies during the transition from primary to permanent dentition. Prediction methods using a probability table or linear regression equation use the sum of the mesiodistal widths of mandibular permanent incisors to predict the mesiodistal width of unerupted permanent teeth. Racial and sexual variations and sexual dimorphism in tooth size have been reported. The objective of this study is to validate Moyer's and Tanaka Johnston's mixed dentition analyses in a contemporary South Indian population., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In this report, we describe a case of proliferative diabetic retinopathy that developed into exudative changes confusing with central serous chorioretinopathy (CSCR) following extensive endolaser pan retinal photocoagulation., Case Description: A 49-year-old male patient with diabetic retinopathy in both eyes presented with vitreous hemorrhage and 6/60 visual acuity in his left eye. Optical coherence tomography (OCT) scans at presentation revealed serous PEDs in both eyes. On day 10 after vitreoretinal surgery and complete peripheral endolaser PRP for the left eye, there was serous retinal detachment (SRD) and an increase in PED heights, mimicking CSCR. No additional treatment was considered. At the three-week post-operative visit, OCT scans revealed that the SRD had resolved and the PED heights had decreased without rupture. At the final follow-up visit, 12 weeks after surgery, the SRD had not recurred, and the PEDs had stabilized. Despite no additional ocular therapy for the right eye, the serous PED height had decreased. The choroidal thickness (CT) at the fovea at various points during the follow-up visits revealed a reduction in both eyes., Conclusion: This case demonstrated the course of SRD, PED, and CT following extensive PRP. These changes may be associated with intraocular VEGF changes. In the presence of SRD and serous PED, the PED morphology may help differentiate the condition from CSCR. Although caution should be exercised when performing PRP during surgery or as an outpatient procedure, the SRD usually resolves without problem., (© 2024. The Author(s).)

Microfluidic concentration gradient generators ( μ -CGGs) are critical in various biochemical assays, including cell migration, drug screening, and antimicrobial susceptibility testing. However, current μ -CGGs rely on integration with flow systems, limiting their scalability and widespread adoption owing to limited infrastructure and technical expertise. Hence, there is a need for flowless diffusional gradient generators capable of standalone operation, thereby improving throughput and usability. In this study, we model such a diffusional μ -CGG as an infinite source-sink system to capture two characteristic timescales: (i) gradient generation dictated by the diffusion timescale and (ii) stability determined by the rate of change in reservoir concentrations. Through finite-element simulations, we explored the influence of various geometric parameters such as the channel length, cross-sectional area, node and reservoir volumes, and the solute diffusivity on these timescales, along with experimental confirmation using fluorescent tracer diffusion. Our results show that while the gradient stability strongly depends on the reservoir volumes, diffusion length, and solute diffusion coefficient, they are independent of the node shape or the shape of the channel cross section. However, gradient profiles were found to be the strong functions of the diffusion length, solute diffusivity, and the geometric pattern of the microfluidic grid. Additionally, we showcased the versatility of the design by generating discrete gradient profiles and combinatorial gradients of two and three solutes, thus improving throughput in a wide range of on-chip biological assays. These findings underscore the potential of our microfluidic device as an easy-to-use, inexpensive, efficient, and high-throughput platform for various on-chip biological assays., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Background: This study aims to assess systemic risk factors in diabetes mellitus (DM) patients and predict diabetic retinopathy (DR) using a Random Forest (RF) classification model., Methods: We included DM patients presenting to the retina clinic for first-time DR screening. Data on age, gender, diabetes type, treatment history, DM control status, family history, pregnancy history, and systemic comorbidities were collected. DR and sight-threatening DR (STDR) were diagnosed via a dilated fundus examination. The dataset was split 80:20 into training and testing sets. The RF model was trained to detect DR and STDR separately, and its performance was evaluated using misclassification rates, sensitivity, and specificity., Results: Data from 1416 DM patients were analyzed. The RF model was trained on 1132 (80%) patients. The misclassification rates were 0% for DR and ~20% for STDR in the training set. External testing on 284 (20%) patients showed 100% accuracy, sensitivity, and specificity for DR detection. For STDR, the model achieved 76% (95% CI-70.7%-80.7%) accuracy, 53% (95% CI-39.2%-66.6%) sensitivity, and 80% (95% CI-74.6%-84.7%) specificity., Conclusions: The RF model effectively predicts DR in DM patients using systemic risk factors, potentially reducing unnecessary referrals for DR screening. However, further validation with diverse datasets is necessary to establish its reliability for clinical use.

Purpose: To study cases diagnosed of myelinated retinal nerve fibres (MRNF) continuous with the optic disc and describe the plausible pathogenic mechanism for the ocular features in Straatsma syndrome., Methods: This retrospective observational study includes clinically diagnosed MRNF cases. MRNF, myopia, and amblyopia defined Straatsma syndrome. MRNF were classified into three types based on location: type 1 in the superior retina, type 2 in the superior and inferior retina, and type 3 in the inferior retina. MRNF size was measured on Optomap ® (Optos, Daytona, UK) images and posterior staphyloma location was noted. Demographics and best-corrected refractive error in logMAR units was recorded. Descriptive statistics and Spearman's corelation test were used to analyse MRNF size's relationship to refractive error and logMAR visual acuity., Results: The study included a total of 19 MRNF eyes from 18 patients. Seventeen (89%) eyes had Straatsma syndrome. Median age was 23.50 [range: 4-75] years. One (6%) patient exhibited bilateral presentation. The median logMAR visual acuity was 0.4 log units (interquartile range: 0.18-1.20) and mean refractive error was -7.21 ± 5.32. Type 2 MRNF ( n  = 14,74%) was the commonest. Average MRNF size was 34.37 ± 40.73 sq.mm. Posterior staphyloma was noted in 17 eyes, all in close MRNF association. Significant positive corelation was noted between logMAR visual acuity and MRNF size ( r  = 0.5, p  = 0.028)., Conclusion: Large size MRNF corelated with poor visual acuity in the study. The paper explains the possible pathogenetic mechanisms for the ocular findings seen in MRNF., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Dysphagia is a leading cause of morbidity in people with amyotrophic lateral sclerosis (PwALS). Previous videofluoroscopic swallowing studies (VFSS) in PwALS do not account for the influence of senescence. We aimed to compare swallowing in PwALS and an age- and sex-matched control group using healthy reference data to define typical and atypical values., Method: We conducted retrospective analysis of VFSS data from 19 PwALS (10 male, M age = 63 years, range: 47-82) compared to control data from a cohort of healthy adults. Participants swallowed 20% w/v liquid barium from thin to extremely thick consistency. Blinded duplicate VFSS analysis using the ASPEKT (Analysis of Swallowing Physiology: Events, Kinematics and Timing) method yielded descriptive statistics for 16 quantitative VFSS parameters by consistency. Mann-Whitney U tests were used to identify significant cohort differences. Additionally, the frequencies of atypical values (in the 25% tails of the reference distribution) were tabulated by cohort and compared using odds ratios., Results: PwALS showed increased frequencies of multiple swallows per bolus, incomplete laryngeal vestibule closure, and reduced hyoid speed across consistencies. By contrast, similar frequencies of atypical values for pharyngeal constriction and residue in both cohorts suggest that age-related changes may contribute to the presence of these features in PwALS., Conclusions: This analysis builds on previous descriptions of swallowing pathophysiology in amyotrophic lateral sclerosis (ALS) by clarifying the extent to which aging may account for some of the atypical findings seen in this patient population. Longitudinal studies are recommended to further differentiate the effects of ALS from age-related changes in swallowing over the course of disease progression.

A left ventricular pseudoaneurysm, an ominous consequence of acute myocardial infarction, poses a significant threat to patient well-being. Prompt and accurate diagnosis is crucial for improving patient outcomes. This report describes diagnostic imaging findings for identifying left ventricular pseudoaneurysms, emphasizing the critical role of cardiac magnetic resonance imaging alongside other modalities. We present two cases of patients with a history of myocardial infarction who presented with palpitations, chest pain, and shortness of breath. Initial 2D echocardiography in both patients revealed aneurysmal dilation of the left ventricle. Cardiac MRI was then performed, confirming the diagnosis in both cases., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background and Objectives: Atogepant is an oral, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine. We evaluated the efficacy of atogepant for the preventive treatment of chronic migraine (CM) in participants with and without acute medication overuse., Methods: This subgroup analysis of the phase 3, 12-week, randomized, double-blind, placebo-controlled PROGRESS trial evaluated adults with a ≥1-year history of CM, ≥15 monthly headache days (MHDs), and ≥8 monthly migraine days (MMDs) during the 4-week baseline period. Participants were randomized (1:1:1) to placebo, atogepant 30 mg twice daily (BID), or atogepant 60 mg once daily (QD) for 12 weeks and were analyzed by acute medication overuse status (triptans/ergots for ≥10 days per month, simple analgesics for ≥15 days per month, or combinations of triptans/ergots/simple analgesics for ≥10 days per month). Outcomes included change from baseline in mean MMDs, MHDs, and monthly acute medication use days; ≥50% reduction in mean MMDs across 12 weeks; and patient-reported outcome (PRO) measures., Results: Of 755 participants in the modified intent-to-treat population, 500 (66.2%) met baseline acute medication overuse criteria (placebo, n = 169 [68.7%]; atogepant 30 mg BID, n = 161 [63.6%]; atogepant 60 mg QD, n = 170 [66.4%]). The least squares mean difference (LSMD) (95% CI) from placebo in MMDs was -2.7 (-4.0 to -1.4) with atogepant 30 mg BID and -1.9 (-3.2 to -0.6) with atogepant 60 mg QD. Mean MHDs (LSMD [95% CI] -2.8 [-4.0 to -1.5] and -2.1 [-3.3 to -0.8]) and mean acute medication use days (LSMD [95% CI] -2.8 [-4.1 to -1.6] and -2.6 [-3.9 to -1.3]) were reduced and a higher proportion of participants achieved ≥50% reduction in MMDs (odds ratio [95% CI] 2.5 [1.5-4.0] and 2.3 [1.4-3.7]) with atogepant 30 mg BID and atogepant 60 mg QD. There was a 52.1%-61.9% reduction in the proportion of atogepant-treated participants meeting acute medication overuse criteria over 12 weeks. Atogepant improved PRO measures. Similar results were observed in the subgroup without acute medication overuse., Discussion: Atogepant was effective in participants with CM, with and without acute medication overuse, as evidenced by reductions in mean MMDs, MHDs, and acute medication use days; reductions in the proportion of participants meeting acute medication overuse criteria; and improvements in PROs., Trial Registration Information: ClinicalTrials.gov NCT03855137. Submitted: February 25, 2019; first patient enrolled: March 11, 2019. clinicaltrials.gov/ct2/show/NCT03855137., Classification of Evidence: This study provides Class II evidence that atogepant reduces mean MMDs, MHDs, and monthly acute medication use days in adult patients with or without medication overuse.

We study the phase behavior of twisted convex n -prisms with n = 3 and 4, via Monte Carlo simulations. Biaxial phases, in untwisted prisms, can be induced by choosing specific geometries of the prisms. However, due to the convexity of the twisted particles, a strong twisting disables the formation of biaxial phases and stabilizes uniaxial nematic and smectic phases. Using the increased volume of the twisted convex particles, we define an effective aspect ratio of the twisted prisms and find a homogeneous phase behavior across the geometry of the prisms' cross-section and even across different shapes of the cross-section. In this representation biaxial phases are found for large aspect ratios, while the low aspect ratio behavior can be compared to the hard cylinder phase diagram. For 3-prisms with a small base angle, we show the influence of the initial configuration; a polar initial configuration results in a (polar) splay nematic phase, whereas a non-polar initial configuration results in a biaxial phase.

Objective: The pharyngeal swallow typically begins within 400 ms following the arrival of a liquid bolus in the pharynx. By contrast, processed food particles aggregate in the valleculae prior to swallow initiation. With solid foods, swallow reaction time (SRT), the interval between bolus passing the ramus of mandible and hyoid burst onset (HYB) can be subdivided into components of vallecular aggregation time (VAT) and the subsequent end of aggregation to hyoid burst interval (EOA-to-HYB). However, expected durations of these timing measures remain unclear. We aimed to study bolus aggregation in healthy swallowing for International Dysphagia Diet Standardisation Initiative Food Levels 5 (minced and moist [MM5]), 6 (soft and bite-sized [SB6]), and 7 (regular [RG7]). Understanding typical patterns and durations of vallecular aggregation with solids in healthy swallowing will inform the identification of impaired swallow timing in patient populations., Design: Twenty healthy adults (10 males, M age = 28 years, range: 23-55 years) swallowed two boluses each of MM5, SB6, and RG7 foods in videofluoroscopy. Blinded duplicate ratings determined bolus location at swallow onset, SRT, VAT, and EOA-to-HYB. Texture-based differences were measured using Friedman's tests. Bolus location was at/above the valleculae at swallow onset for 85% of boluses, with no differences by texture. SRT, VAT, and EOA-to-HYB did not vary by texture, with overall median values (interquartile range) of 99 ms (-66 to 743 ms) for SRT, 347 ms (66 to 891 ms) for VAT, and -132 ms (-231 to -83 ms) for EOA-to-HYB., Conclusions: These data corroborate prior evidence that it is not unusual for food particles to aggregate in the valleculae prior to swallow initiation in healthy swallowing. However, durations of vallecular aggregation are typically < 1 s in healthy adults.

Background: A composite endpoint (CEP) is a measure comprising 2 or more separate component outcomes. The use of these constructs is increasing. We sought to conduct a systematic review on the usage, quality of reporting, and appropriate use of CEPs in spine surgery research., Methods: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Articles reporting randomized controlled trials of a spine surgery intervention using a CEP as a primary outcome were included. We assessed the quality of CEP reporting, appropriateness of CEP use, and correspondence between CEP treatment effect and component outcome treatment effect in the included trials., Results: Of 2,321 initial titles, 43 citations were included for analysis, which reported on 20 unique trials. All trials reported the CEP construct well. In 85% of trials, the CEP design was driven by US Food and Drug Administration guidance. In the majority of trials, the reporting of CEP results did not adhere to published recommendations: 43% of tests that reported statistically significant results on component outcomes were not statistically significant when adjusted for multiple testing. 67% of trials did not meet appropriateness criteria for CEP use. In addition, CEP treatment effect tended to be 6% higher than the median treatment effect for component outcomes., Conclusion: Given that CEP analysis was not appropriate for the majority of spine surgery trials and the inherent challenges in the reporting and interpretation of CEP analysis, CEP use should not be mandated by regulatory bodies in spine surgery trials., Level of Evidence: Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B102)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The result of increased occlusal stresses might be fractures in the teeth. It is still unclear how possible risk factors may affect the occurrence of tooth cracks after dental implants with prostheses in nonendodontically restored teeth., Aim: To evaluate the correlation of dental implants with prostheses as a risk factor for the development of cracks in teeth restored nonendodontically., Materials and Methods: Records of 414 patients with 570 teeth who underwent tooth restoration nonendodontically were obtained. The data was obtained regarding the number of implants with prostheses placed before the diagnosis of cracks in nonendodontically treated teeth, the time interval between placement of dental implants, and appearance of cracks in teeth, location of dental implants with respect to cracked tooth., Results: Cracks in tooth was observed in 160 teeth out of 570 teeth evaluated (28.07%) and 144 patients out of 414 patients (34.78%). It was observed that out of 160 teeth with cracks, 66 teeth (41.25%) had cracks after placement of dental implants with prosthesis., Conclusion: Placement of a dental implant with a prosthesis can be a risk factor for appearing cracks in teeth treated nonendodontically., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: The usual procedure for nasolacrimal duct obstruction is dacryocystorhinostomy (DCR). Flap-based DCR techniques lead to better surgical outcome provided flaps do not dislocate in the post-operative period., Objectives: This study was conducted to compare gelfoam with merocel tamponade for fixation of mucosal flaps in endoscopic DCR., Materials and Method: Merocel tamponade was used for fixation of flaps in 26 patients. Gelfoam was used in 26 patients, and surgical results were compared., Results: The surgical success rate was greater in merocel tamponade fixation with less complications., Conclusion: Merocel tamponade can be used successfully for mucosal flap fixation in endoscopic DCR for better surgical outcome., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Objective: To assess the association between ambient heat and all-cause and cause-specific emergency department (ED) visits and acute hospitalizations among Medicare beneficiaries in the conterminous United States., Design: Retrospective cohort study., Setting: Conterminous US from 2008 and 2019., Participants: 2% random sample of all Medicare fee-for-service beneficiaries eligible for Parts A, B, and D., Main Outcome Measures: All-cause and cause-specific (cardiovascular, renal, and heat-related) ED visits and unplanned hospitalizations were identified using primary ICD-9 or ICD-10 diagnosis codes. We measured the association between ambient temperature - defined as daily mean temperature percentile of summer (June through September) - and the outcomes. Hazard ratios and their associated 95% confidence intervals were estimated using multivariable Cox proportional hazards regression, adjusting for individual level demographics, comorbidities, healthcare utilization factors and zip-code level social factors., Results: Among 809,636 Medicare beneficiaries (58% female, 81% non-Hispanic White, 24% <65), older beneficiaries (aged ≥65) exposed to >95th percentile temperature had a 64% elevated adjusted risk of heat-related ED visits (HR [95% CI], 1.64 [1.46,1.85]) and a 4% higher risk of all-cause acute hospitalization (1.04 [1.01,1.06]) relative to <25th temperature percentile. Younger beneficiaries (aged <65) showed increased risk of heat-related ED visits (2.69 [2.23,3.23]) and all-cause ED visits (1.03 [1.01,1.05]). The associations with heat related events were stronger in males and individuals dually eligible for Medicare and Medicaid. No significant differences were observed by climatic region. We observed no significant relationship between temperature percentile and risk of CV-related ED visits or renal-related ED visits., Conclusions: Among Medicare beneficiaries from 2008 to 2019, exposure to daily mean temperature ≥ 95th percentile was associated with increased risk of heat-related ED visits, with stronger associations seen among beneficiaries <65, males, and patients with low socioeconomic position. Further longitudinal studies are needed to understand the impact of heat duration, intensity, and frequency on cause-specific hospitalization outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic ethanol dependence and withdrawal activate corticotropin releasing factor (CRF)-containing GABAergic neurons in the medial prefrontal cortex (mPFC), which tightly regulate glutamatergic pyramidal neurons. Using male CRF1:GFP reporter mice, we recently reported that CRF1-expressing (mPFC CRF1+ ) neurons predominantly comprise mPFC prelimbic layer 2/3 pyramidal neurons, undergo profound adaptations following chronic ethanol exposure, and regulate anxiety and conditioned rewarding effects of ethanol. To explore the effects of acute and chronic ethanol exposure on glutamate transmission, the impact of chronic alcohol on spine density and morphology, as well as persistent changes in dendritic-related gene expression, we employed whole-cell patch-clamp electrophysiology, diOlistic labeling for dendritic spine analysis, and dendritic gene expression analysis to further characterize mPFC CRF1+ and mPFC CRF1- prelimbic layer 2/3 pyramidal neurons. We found increased glutamate release in mPFC CRF1+ neurons with ethanol dependence, which recovered following withdrawal. In contrast, we did not observe significant changes in glutamate transmission in neighboring mPFC CRF1- neurons. Acute application of 44 mM ethanol significantly reduced glutamate release onto mPFC CRF1+ neurons, which was observed across all treatment groups. However, this sensitivity to acute ethanol was only evident in mPFC CRF1- neurons during withdrawal. In line with alterations in glutamate transmission, we observed a decrease in total spine density in mPFC CRF1+ neurons during dependence, which recovered following withdrawal, while again no changes were observed in mPFC CRF- neurons. Given the observed decreases in mPFC CRF1+ stubby spines during withdrawal, we then identified persistent changes at the dendritic gene expression level in mPFC CRF1+ neurons following withdrawal that may underlie these structural adaptations. Together, these findings highlight the varying responses of mPFC CRF1+ and mPFC CRF1- cell-types to acute and chronic ethanol exposure, as well as withdrawal, revealing specific functional, morphological, and molecular adaptations that may underlie vulnerability to ethanol and the lasting effects of ethanol dependence., Competing Interests: None., (© 2024 The Authors.)

Importance: Despite biological plausibility, very few epidemiologic studies have investigated the risks of clinically significant bleeding events due to particulate air pollution., Objective: To measure the independent and synergistic effects of PM 2.5 exposure and anticoagulant use on serious bleeding events., Design: Retrospective cohort study (2008-2016)., Setting: Nationwide Medicare population., Participants: A 50% random sample of Medicare Part D-eligible Fee-for-Service beneficiaries at high risk for cardiovascular and thromboembolic events., Exposures: Fine particulate matter (PM 2.5 ) and anticoagulant drugs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin)., Main Outcomes and Measures: The outcomes were acute hospitalizations for gastrointestinal bleeding, intracranial bleeding, or epistaxis. Hazard ratios and 95% CIs for PM 2.5 exposure were estimated by fitting inverse probability weighted marginal structural Cox proportional hazards models. The relative excess risk due to interaction was used to assess additive-scale interaction between PM 2.5 exposure and anticoagulant use., Results: The study cohort included 1.86 million high-risk older adults (mean age 77, 60% male, 87% White, 8% Black, 30% anticoagulant users, mean PM 2.5 exposure 8.81 μg/m 3 ). A 10 μg/m 3 increase in PM 2.5 was associated with a 48% (95% CI: 45%-52%), 58% (95% CI: 49%-68%) and 55% (95% CI: 37%-76%) increased risk of gastrointestinal bleeding, intracranial bleeding, and epistaxis, respectively. Significant additive interaction between PM 2.5 exposure and anticoagulant use was observed for gastrointestinal and intracranial bleeding., Conclusions: Among older adults at high risk for cardiovascular and thromboembolic events, increasing PM 2.5 exposure was significantly associated with increased risk of gastrointestinal bleeding, intracranial bleeding, and epistaxis. In addition, PM 2.5 exposure and anticoagulant use may act together to increase risks of severe gastrointestinal and intracranial bleeding. Thus, clinicians may recommend that high-risk individuals limit their outdoor air pollution exposure during periods of increased PM 2.5 concentrations. Our findings may inform environmental policies to protect the health of vulnerable populations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rachel C. Nethery reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies., Target Product Profile: Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings., Conclusion: Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease., (© 2024. The Author(s).)

Motivated by efforts to return humanity to the Moon, three cases are reviewed for X-ray astronomy from the lunar surface: (i) facilitation of ambitious engineering designs including high-throughput telescopes, long focal length optics and X-ray interferometery; (ii) occultation studies and the gain they enable in astrometric precision; and (iii) multi-messenger time-domain coordinated observations. The potential benefits of, and challenges presented by, operating from the Moon are discussed. Some of these cases have relatively low mass budgets and could be conducted as early pathfinders, while others are more ambitious and will likely need to await improvements in technology or well-developed lunar bases. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

Objective: To synthesize community and healthcare informants' perspectives on contextual considerations and tailoring recommendations for high-quality, sustainable implementation of evidence-based practices (EBPs) for managing hypertension (HTN) in a multiethnic safety-net population., Design: Structured focus-group discussions and semistructured qualitative interviews., Background: High-quality, sustainable implementation of HTN-related EBPs can promote equitable care. Implementation challenges extend beyond individual patients to span multiple levels of context. Few studies have systematically engaged community and healthcare perspectives to inform the design of HTN intervention trials., Setting: A large safety-net healthcare system., Participants/methods: We conducted four structured discussions with each of five race- or ethnicity-specific community action boards (CABs) to understand community members' HTN-related norms, assets, needs, and experiences across local healthcare systems. We interviewed 41 personnel with diverse roles in our partnered healthcare system to understand the system's HTN-related strengths and needs. We solicited EBP tailoring recommendations from both groups. We summarized the findings using rapid content analysis., Results: Participants identified contextual considerations spanning seven themes: social determinants, healthcare engagement, clinical interaction, system operations, standardization, patient education, and partnerships and funding. They offered tailoring recommendations spanning nine themes: addressing complex contexts, addressing social needs, system operations, healthcare system training and resources, linguistic and cultural tailoring, behavioral engagement, relational engagement, illness-course engagement, and community partnerships., Conclusions: Engaging community and healthcare informants can ground implementation in the policy, community, healthcare system, clinical, and interpersonal contexts surrounding diverse patients at risk for disparities. Such grounding can reframe inequitable implementation as a multilevel social problem facing communities and healthcare systems, rather than individuals., Competing Interests: Conflict of Interest: Sandesara, Wali, Park, and Brown: Receive salary support from the partnered healthcare system for this study.

Background: There are still certain gaps in the research that need to be filled despite the fact that numerous studies have looked into the transformation of odontogenic cysts into neoplastic lesions. To identify pertinent research that had been published and to synthesise the available data and provide an overview of the current body of knowledge, this review also sought to do so., Materials and Methods: Adopting the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a search strategy was implemented across several online databases to search for relevant articles as per the defined selection criterion., Results: After the search strategy was complete, 31 studies were chosen. Men tended to have more cancer than women. Swelling and discomfort were the primary pathology-related complaints. Although two cases were not detailed, radiologically, well-defined and poorly defined borders were reported in 18 and 11 participants, respectively. Squamous cell carcinoma with good differentiation ( n = 12) was the most common cancer kind. More than 74% of patients were still living 6 months to 10 years following follow-up, four (12.90%) experienced recurrences and/or metastases and two (6.45%) experienced a disease-related mortality between 2 months and a year., Conclusion: Prompt surgical follow-ups and cautious excision of odontogenic cysts are essential to avoiding neoplastic change and recurrence. Future research is required to look at possible reasons why odontogenic cysts can convert neoplastically., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Oral and Maxillofacial Pathology.)

Background: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation., Methods: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments., Results: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; P interaction =0.009)., Conclusions: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings., Competing Interests: Disclosures Disclosures provided by Dr Nguyen in compliance with American Heart Association annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor-coi-disclosures. Dr Arnold reports compensation from Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Medtronic, Novo Nordisk, and Amgen for consultant services. Dr Lester reports a provisional patent for Methods and compositions for disrupting tau aggregates. Dr Touze reports compensation from Elsevier for other services and employment by Caen. J.E. Kaufman reports grants from Goldschmidt Jacobson-Stiftung. Dr Traenka reports travel support from Bayer Healthcare. Dr Aguiar de Sousa reports compensation from Daiichi Sankyo, Bayer, AstraZeneca, Johnson & Johnson, and Fundação Bial for other services; compensation from the University of British Columbia for data and safety monitoring services; compensation from Organon & Co for consultant services. Dr Rosa reports grants from Merck Sharp & Dohme Corporation. Dr Field reports compensation from HLS Therapeutics, AstraZeneca Canada, and Roche for consultant services; service as a board member for Destine Health; and compensation from the Canadian Medical Protective Association for expert witness services; and grants from Bayer. Dr Leker reports compensation from Medtronic, Ischemaview, Bayer, Abbott Diabetes Care, Biogen, Janssen Biotech, and Boehringer Ingelheim for other services. Dr Nolte reports compensation from Daiichi Sankyo Europe GmbH, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Alexion Pharmaceuticals for consultant services; and compensation from AstraZeneca, Abbott Canada, Deutsches Zentrum für Neurodegenerative Erkrankungen, Novartis, Portola Pharmaceuticals, Deutsches Zentrum für Herz-Kreislaufforschung, and Novartis for other services. Dr Poppe reports grants from Foundation Brain Canada, Heart and Stroke Foundation of Canada, and Stryker; and compensation from Roche for other services. Dr Liebeskind reports compensation from Medtronic, Genentech, Cerenovus, Stryker, and Rapid Medical Ltd, for consultant services. B. Mac Grory reports grants from the National Institutes of Health; employment by Duke University Medical Center; compensation from Bayer for other services; grants from the American Heart Association, Duke Bass Connections, and the Duke Office of Physician Scientist Development. Dr Al Kasab reports compensation from Stryker for other services and employment by Medical University of South Carolina. Dr Kicielinski reports compensation from Stryker, Penumbra Inc, Medtronic, and MicroVention Inc, for other services; travel support from MicroVention Inc; and employment by Medical University of South Carolina and Elsevier. Dr de Havenon reports stock options in TitinKM and Certus; grants from the National Institutes of Health; and compensation from Novo Nordisk for consultant services. Dr Siegler reports grants from Philips and employment by the University of Chicago. Dr Willey reports compensation from Edwards Lifesciences Corporation and Abbott Fund for end point review committee services; compensation from Uptodate for other services; and compensation from the Abbott Laboratories for consultant services. Dr Sharma reports a provisional patent for a stroke etiology classifier algorithm and grants from the National Institutes of Health Clinical Center. Dr Martins reports compensation from Pfizer, Medtronic, Servier Affaires Medicales, Daiichi Sankyo, Bayer, Novo Nordisk, Novartis, Penumbra Inc, and Boehringer Ingelheim for other services. Dr Simpkins reports grants from the National Institutes of Health. Dr Stretz reports grants from Massachusetts General Hospital. Dr Furie reports compensation from Janssen Biotech for consultant services. The other authors report no conflicts

Objective: To evaluate unmet needs among individuals with episodic migraine (EM) in the United States (US)., Background: Data are limited on the impact of headache frequency (HF) and preventive treatment failure (TF) on the burden of migraine in the US., Methods: A retrospective, cross-sectional analysis of 2019 National Health and Wellness Survey (NHWS) data was conducted from an opt-in online survey that identified respondents (aged ≥18 years) in the US with self-reported physician-diagnosed migraine. Participants were stratified by HF (low: 0-3 days/month; moderate-to-high: 4-14 days/month) and prior preventive TF (preventive naive; 0-1 TF; ≥2 TFs). Comparisons were conducted between preventive TF groups using multivariable regression models controlling for patient demographic and health characteristics., Results: Among individuals with moderate-to-high frequency EM, the NHWS identified 397 with ≥2 TFs, 334 with 0-1 TF, and 356 as preventive naive. The 36-item Short-Form Health Survey (version 2) Physical Component Summary scores were significantly lower among those with ≥2 TFs, at a mean (standard error [SE]) of 41.4 [0.8] versus the preventive-naive 46.8 [0.9] and 0-1 TF 44.5 [0.9] groups; p < 0.001 for both). Migraine Disability Assessment Scale scores were significantly higher in the ≥2 TFs, at a mean (SE) of 37.7 (3.9) versus preventive-naive 26.8 (2.9) (p < 0.001) and 0-1 TF 30.1 (3.3) (p = 0.011) groups. The percentages of time that respondents experienced absenteeism (mean [SE] 21.6% [5.5%] vs. 13.4% [3.6%]; p = 0.022), presenteeism (mean [SE] 55.0% [8.3%] vs. 40.8% [6.5%]; p = 0.015), overall work impairment (mean [SE] 59.4% [5.6%] vs. 45.0% [4.4%]; p < 0.001), and activity impairment (mean [SE] 56.8% [1.0%] vs. 44.4% [0.9%]; p < 0.001) were significantly higher in the ≥2 TFs versus preventive-naive group. Emergency department visits (preventive-naive, p = 0.006; 0-1 TF, p = 0.008) and hospitalizations (p < 0.001 both) in the past 6 months were significantly higher in the ≥2 TFs group. Direct and indirect costs were significantly higher in the ≥2 TFs (mean [SE] $24,026 [3460]; $22,074 [20]) versus 0-1 TF ($10,897 [1636]; $17,965 [17]) and preventive-naive ($11,497 [1715]; $17,167 [17]) groups (p < 0.001 for all). Results were similar in the low-frequency EM group., Conclusions: In this NHWS analysis, individuals with more prior preventive TFs experienced significantly higher humanistic and economic burden regardless of HF., (© 2024 AbbVie and The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Ensuring the security and privacy of patient data is a critical concern in the healthcare industry. The growing utilization of electronic data transmission and storage in medical records has amplified apprehensions about data security. However, due to varying stakeholder interests, not all data can be freely shared, necessitating the development of secure protocols., Materials and Methods: This study presents a highly secure protocol that integrates blockchain technology, patient biometric information, and robust cryptographic algorithms (elliptic curve cryptography (ECC) and advanced encryption algorithm (AEC)) to facilitate data encryption and decryption. The protocol encompasses secure login, secure key sharing, and data sharing mechanisms among miners, offering comprehensive security measures. To validate the effectiveness of the proposed protocol, both informal and formal security analyses are conducted. The security protocol description language in Scyther is utilized to evaluate the protocol's resilience against attacks., Results: The culmination of this research is a secure protocol that leverages blockchain technology and ECC for the secure storage and sharing of medical records. The protocol covers all stages, including system setup, user registration, login mechanisms, key exchange between users and blockchain, communication between blockchains, and interaction with other miners, with a steadfast emphasis on security. Furthermore, the protocol's communication and computation costs are assessed, with a comparison to existing blockchain-based schemes. Informal proofs establish the protocol's security against common attacks faced by medical institutions. Formal simulation of the protocol using the Scyther tool provides definitive evidence of its resistance to attacks., Conclusions: As a result, this protocol presents a viable real-time implementation solution for safeguarding patient data within the healthcare domain, representing a significant contribution to data security., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Education and Health Promotion.)

Background: Long noncoding RNAs (lncRNAs) are RNA transcripts over 200 nucleotides in length that do not code for proteins. Initially considered a genomic mystery, an increasing number of lncRNAs have been shown to have vital roles in physiological and pathological conditions by regulating gene expression through diverse mechanisms depending on their subcellular localization. Dysregulated angiogenesis is responsible for various vascular oculopathies, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and corneal neovascularization. While anti-VEGF treatment is available, it is not curative, and long-term outcomes are suboptimal, and some patients are unresponsive. To better understand these diseases, researchers have investigated the role of lncRNAs in regulating angiogenesis and models of vascular oculopathies. This review summarizes recent research on lncRNAs in ocular angiogenesis, including the pro-angiogenic lncRNAs ANRIL, HOTAIR, HOTTIP, H19, IPW, MALAT1, MIAT, NEAT1, and TUG1, the anti-angiogenic lncRNAs MEG3 and PKNY, and the human/primate specific lncRNAs lncEGFL7OS, discussing their functions and mechanisms of action in vascular oculopathies., (© 2024. The Author(s).)

Competing Interests: Competing interests: None declared.

Competing Interests: Intérêts concurrents:: Nikki Bozinoff déclare avoir reçu des bourses de recherche de l’Academic Health Sciences Alternate Funding Program (Programme de financement alternatif de l’Académie des sciences de la santé), des Instituts de recherche en santé du Canada et de la communauté philanthropique womenmind (indépendamment du manuscrit soumis). La Dre Bozinoff a reçu une subvention du National Institute on Drug Abuse (Institut national sur la toxicomanie) (R25-DA037756), en appui du présent manuscrit, ainsi que des honoraires du Collège des médecins de famille de l’Ontario pour des activités éducatives et un paiement du Centre de toxicomanie et de santé mentale pour l’élaboration de matériel de perfectionnement professionnel continu indépendamment du présent manuscrit. Aucun autre intérêt concurrent n’a été déclaré.

Objectives: To find the prevalence of knowledge of arteriovenous fistula (AVF) self-care, its characteristics, and associated factors among hemodialysis patients and summarize the findings of various domains of AVF self-care in south Asian countries., Methods: The systematic literature search was performed on online databases and additional sources to retrieve published articles on AVF self-care. We estimated the pooled prevalence using a random effects model in meta-analysis. Additionally, thematic knowledge regarding various aspects of AVF self-care was narratively summarized., Results: Among the articles retrieved seven studies met our inclusion and exclusion criteria. The prevalence of AVF self-care in individual studies ranged from 59% to 99%, with an overall random pooled prevalence of 81% (95% CI, 68% to 94%). Major factors associated with self-care of AVF knowledge included patients' educational status, age, vintage of hemodialysis, and healthcare personnel's advice., Discussion: Knowledge scarcity regarding potential measures of AVF self-care obligates the need for continuous education in hemodialysis patients. A multidisciplinary approach is vital to enhance self-care from pre- to post-creation of AVF in hemodialysis patients as well as their caregivers in order to prolong the patency rates and decrease the subsequent morbidity and mortality due to failure of AVF., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The COVID-19 pandemic has accelerated the growing global interest in the role of augmented and virtual reality in surgical training. While this technology grows at a rapid rate, its efficacy remains unclear. To that end, we offer a systematic review of the literature summarizing the role of virtual and augmented reality on spine surgery training., Methods: A systematic review of the literature was conducted on May 13th, 2022. PubMed, Web of Science, Medline, and Embase were reviewed for relevant studies. Studies from both orthopedic and neurosurgical spine programs were considered. There were no restrictions placed on the type of study, virtual/augmented reality modality, nor type of procedure. Qualitative data analysis was performed, and all studies were assigned a Medical Education Research Study Quality Instrument (MERSQI) score., Results: The initial review identified 6752 studies, of which 16 were deemed relevant and included in the final review, examining a total of nine unique augmented/virtual reality systems. These studies had a moderate methodological quality with a MERSQI score of 12.1 + 1.8; most studies were conducted at single-center institutions, and unclear response rates. Statistical pooling of the data was limited by the heterogeneity of the study designs., Conclusion: This review examined the applications of augmented and virtual reality systems for training residents in various spine procedures. As this technology continues to advance, higher-quality, multi-center, and long-term studies are required to further the adaptation of VR/AR technologies in spine surgery training programs.

Purpose: To study the role of artificial intelligence (AI) in developing diabetic macular edema (DME) management recommendations by creating and comparing responses to clinicians in hypothetical AI-generated case scenarios. The study also examined whether its joint recommendations followed national DME management guidelines., Methods: The AI hypothetically generated 50 ocular case scenarios from 25 patients using keywords like age, gender, type, duration and control of diabetes, visual acuity, lens status, retinopathy stage, coexisting ocular and systemic co-morbidities, and DME-related retinal imaging findings. For DME and ocular co-morbidity management, we calculated inter-rater agreements (kappa analysis) separately for clinician responses, AI-platforms, and the "majority clinician response" (the maximum number of identical clinician responses) and "majority AI-platform" (the maximum number of identical AI responses). Treatment recommendations for various situations were compared to the Indian national guidelines., Results: For DME management, clinicians (ĸ=0.6), AI platforms (ĸ=0.58), and the 'majority clinician response' and 'majority AI response' (ĸ=0.69) had moderate to substantial inter-rate agreement. The study showed fair to substantial agreement for ocular co-morbidity management between clinicians (ĸ=0.8), AI platforms (ĸ=0.36), and the 'majority clinician response' and 'majority AI response' (ĸ=0.49). Many of the current study's recommendations and national clinical guidelines agreed and disagreed. When treating center-involving DME with very good visual acuity, lattice degeneration, renal disease, anaemia, and a recent history of cardiovascular disease, there were clear disagreements., Conclusion: For the first time, this study recommends DME management using large language model-based generative AI. The study's findings could guide in revising the global DME management guidelines., (© 2024. The Author(s).)

This is a non-randomized, open-label, prospective single-arm interventional multicentric study conducted between 2021 and 2022 at three different centers situated in Pune, India. It was conducted to evaluate the efficacy and safety of the Sitcom ® tablet ( Euphorbia prostrata 100 mg) once daily and Sitcom ® cream ( Euphorbia prostrata 1%w/w) for 14 days in hemorrhoids during pregnancy. The endpoints were to assess hemorrhoidal symptoms relief during the follow-up periods (one, two, four, and eight weeks and 30 days postpartum), relapse of symptoms, improvement in the disease condition at week two and 30 days postpartum, and adverse events. A total of 100 patients (mean age 24.1 years) were included; the majority (71.0%) had mild per-rectal bleeding, 69.0% with mild itching and 46.0% with moderate pain during defecation. The mean score of per-rectal bleeding and pain at defecation showed a significant reduction at each visit (86.6% and 49.3% (two weeks), 95.3% and 59.9% (four weeks), and 100% and 77.6% (eight weeks)). The mean pain score at defecation, itching, exudates, and swelling showed a significant reduction of 77.6%, 96.9%, 100%, and 84.5% at eight weeks ( p <0.001). After two weeks and post postpartum follow-up, >90% and 100% good to excellent overall improvement in the disease condition were noted, respectively. No adverse events in the mother or newborn were noted. This pivotal study underscores the potential of a combination therapy with Euphorbia prostrate 100 mg tablet and cream 1% as a potential solution for managing the distressing burden of hemorrhoids in pregnant women. Furthermore, these observations will empower clinicians in the judicious selection of the most suitable course of action for hemorrhoid management during pregnancy., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Porwal et al.)

Objective: To measure the association between ambient heat and hypoglycemia-related emergency department visit or hospitalization in insulin users., Research Design and Methods: We identified cases of serious hypoglycemia among adults using insulin aged ≥65 in the U.S. (via Medicare Part A/B/D-eligible beneficiaries) and Taiwan (via National Health Insurance Database) from June to September, 2016-2019. We then estimated odds of hypoglycemia by heat index (HI) percentile categories using conditional logistic regression with a time-stratified case-crossover design., Results: Among ∼2 million insulin users in the U.S. (32,461 hypoglycemia case subjects), odds ratios of hypoglycemia for HI >99th, 95-98th, 85-94th, and 75-84th percentiles compared with the 25-74th percentile were 1.38 (95% CI, 1.28-1.48), 1.14 (1.08-1.20), 1.12 (1.08-1.17), and 1.09 (1.04-1.13) respectively. Overall patterns of associations were similar for insulin users in the Taiwan sample (∼283,000 insulin users, 10,162 hypoglycemia case subjects)., Conclusions: In two national samples of older insulin users, higher ambient temperature was associated with increased hypoglycemia risk., (© 2024 by the American Diabetes Association.)