LovesCompany: evaluating the safety and feasibility of a mental health-focused online community for adolescents.

Background: Adolescents are at risk for mental health (MH) disorders but are unlikely to seek services and may be reluctant to talk about their MH. An anonymous, online MH-focused community could help reduce suffering. However, online forums can also promote negative behaviours such as cyberbullying. This study aimed to evaluate the safety and feasibility of an online community - LovesCompany - to improve MH outcomes for adolescents.Methods: American adolescents (14-17 years) were recruited through social media. Eligible participants were randomised to LovesCompany or a placebo MH resource site. Outcomes were assessed every other week for six months, and at twelve months. Multilevel models assessed group differences in depression, anxiety, and suicidal ideation. A subgroup of participants participated in qualitative interviews.Results: Participants (N = 202) were mostly female (70%), White non-Hispanic (69%), and cisgender (80%). There were no instances of inappropriate behaviour such as bullying or posting explicit content. Symptoms for both groups improved over time. Participants appreciated hearing others' experiences and valued the opportunity to offer support.Conclusion: Although adolescents are often resistant to MH treatment, they appear to be interested in anonymous, online, MH-focused conversation, and can benefit from giving and seeking support. Finding a balance between an appealing user experience, ethical considerations, and resource needs is challenging.

Estimating the Time Toxicity of Contemporary Systemic Treatment Regimens for Advanced Esophageal and Gastric Cancers.

(1) Background: The purpose of this study was to evaluate the time toxicity, or time spent in health care, of immunotherapy- versus chemotherapy-based regimens for metastatic esophageal and gastric cancers. (2) Methods: A literature search was conducted, and 18 phase III clinical trials of immune checkpoint inhibitors were selected for analysis. Health care days were calculated based on the number of days associated with receiving therapy and the adverse events reported in the clinical trials. Both the number of health care days and the median overall survival were compared among chemotherapy-only, immunotherapy-only, and chemo-immunotherapy regimens across this cohort of drug registration trials. (3) Results: The estimated median number of health care days was 37 (range of 7-52) days, or 1.2 (range of 0.2-1.7) months, compared to a median survival of 10.2 months across these 18 studies. For the chemotherapy-only regimens, the median number of health care days was 39 (range of 21-51) days, and for chemo-immunotherapy, it was 39 (range of 30-52) days. The immunotherapy-only regimens had fewer days, a median of 28 (range of 24-41), p < 0.05, compared to the other two arms. (4) Conclusions: The chemo-immunotherapy regimens did not add time toxicity compared to chemotherapy alone. The immunotherapy-only regimens had lower time toxicity compared to chemotherapy alone. In the setting of decreased time toxicity and improved overall survival, further development of immunotherapy-based regimens could improve outcomes in advanced esophageal and gastric cancers.

Large Urethral Diverticular Calculus Clinically Mimicking a Metastatic Deposit in a Case of Ovarian Mass.

Calculus in the urethra of the female is very unusual. The patient remains asymptomatic or uncommonly presents with symptoms of dysuria, post-void urinary dribbling, and dyspareunia. If asymptomatic, it can be diagnosed incidentally on gynecological examination. Being hard in consistency, it may mimic metastatic lesion. We present a case of a female who presented to us for management of ovarian mass. On routine examination there was a hard mass in her vagina which was suspected to be a metastatic lesion. This mass on evaluation came out to be a urethral diverticulum with a large calculus. Very large urethral calculus are a very rare presentation in a female.

Comparative Assessment of Periodontal Status in Subjects with and without Polycystic Ovary Syndrome and its Correlation with Body Mass Index: A Cross-Sectional Study.

New avenues for research have opened, which assess the influence of systemic disease on periodontium and vice versa. To find the correlation between polycystic ovary syndrome (PCOS) and periodontium by assessing clinical parameters [plaque index (PI), probing depth, periodontal disease index (PDI)] and the anthropological parameter [body mass index (BMI)] and to find the correlation between body mass index and periodontal disease index in subjects with and without PCOS. Sixty females comprising 30 with PCOS and 30 without PCOS were selected. Clinical, anthropological, and radiological assessment was done. Double blinding was incorporated. There was a statistically highly significant difference in mean age, mean PI, and mean PDI (P < 0.001) in PCOS group when compared to those without PCOS group by unpaired t-test for inter-group analysis. A statistically significant difference was found in mean probing depth and mean BMI (P < 0.05) in PCOS group when compared to those without PCOS group by unpaired t-test for inter-group analysis. No statistically significant correlation was found between mean PDI and mean BMI in PCOS and non-PCOS group subjects using Spearman's rank correlation. Women suffering from PCOS may be at a heightened risk for developing periodontal disease as our study re-establishes this association with respect to some periodontal parameters. With such a result, general practitioners/gynecologists can be encouraged to refer cases of PCOS to periodontists for early detection, prevention of periodontal disease, and maintenance of periodontal health.

Sirenomelia in Twin Pregnancy: A Case Report.

Sirenomelia is a rare congenital disorder that was once thought to be a severe case of caudal regression but is now thought to be entirely separate. It is often referred to as the "mermaid syndrome" because it causes the lower limbs to atrophy to varying degrees, giving the impression of a mermaid's tail or fin. The syndrome is often viewed as fatal due to the accompanying visceral deformities. Our case was a live born, delivered at term by caesarean section, to a 30-year-old third gravida having twin pregnancy. Examination of the baby revealed caudal dysgenesis with fusion of lower limbs, non-identifiable external genitalia and anus. The infant survived for 11 hours after birth. We report this case due to their rarity and term live birth. While sirenomelia is uncommon, the absence of distinct lower limbs on ultrasonography in the presence of oligo or anhydramnios may prompt consideration of the diagnosis of sirenomelia.

Evaluation of the Impact of Different Instrumentation Techniques on the Incidence of Postoperative Pain in Patients Undergoing Root Canal Treatment.

BACKGROUND: Postoperative pain is a common concern in root canal treatment, and the choice of instrumentation technique can significantly impact patient comfort. This study aimed to evaluate the impact of different instrumentation techniques on the incidence of postoperative pain in patients undergoing root canal treatment. METHODS: A randomized controlled trial was conducted on 208 patients randomly assigned to four groups: step-back preparation, crown-down preparation, hybrid technique, and conventional instrumentation. Pain intensity was assessed using a verbal rating scale (VRS) at six, 12, 24, 48, and 72 hours postoperatively. Data were analyzed using appropriate statistical methods. RESULTS: The mean pain scores and standard deviations (SDs) were calculated for each instrumentation technique at different time intervals. At six hours, the step-back preparation group reported a mean pain score of 2.3 (SD = 0.8), the crown-down preparation group had a score of 2.8 (SD = 0.9), the hybrid technique group had a score of 2.5 (SD = 0.7), and the conventional instrumentation group had a score of 3.1 (SD = 0.1). The differences in pain scores between the groups were statistically significant at all time intervals (p < 0.05). CONCLUSION: The choice of instrumentation technique significantly influenced the incidence of postoperative pain in root canal treatment. The step-back preparation technique was associated with lower pain intensity than the crown-down preparation, hybrid technique, and conventional instrumentation. These findings highlight the importance of considering the instrumentation technique to optimize patient comfort during and after root canal treatment.

Turner Syndrome and Neurofibromatosis 1: Rare Co-Existence with Important Clinical Implications.

A 16.5-year-old Indian female presented with secondary amenorrhoea, cubitus valgus, scoliosis and multiple lentigines on the face. Karyotyping revealed mosaic Turner syndrome (TS) with 45, X/46, X iXq. She also had multiple café-au-lait macules and axillary freckles but no neurofibroma and did not fulfil the classic criteria for diagnosis of Neurofibromatosis-1 (NF1). Many of her macules were smaller than 15 mm in diameter, which might be due to her hypoestrogenic state. However, exome-sequencing found a pathologic variant consistent with NF1. She was started on daily oral estrogen, and oral progesterone for 10 days every month with close monitoring for neurofibroma and/or glioma expansion. Co-occurrence of NF1 and TS is extremely rare, TS and NF1 can both affect growth and puberty, cause different cutaneous and skeletal deformities, hypertension, vasculopathy and learning disabilities. Our case highlights the need for genetic testing in some cases with NF1 who do not strictly fulfil the NIH diagnostic criteria. We also emphasize the need for close monitoring during therapy with growth hormone, estrogen and progesterone due to the potential risk of tumour expansion in NF1.

Safety and Effectiveness of Miltefosine in Post-Kala-Azar Dermal Leishmaniasis: An Observational Study.

Background: Post-kala-azar dermal leishmaniasis (PKDL) is a dermal complication of visceral leishmaniasis. Oral miltefosine (MF) is the first-line treatment for PKDL patients in South Asia. This study assessed the safety and effectiveness of MF therapy after 12 months of follow-up to explore more precise data. Methods: In this observational study, 300 confirmed PKDL patients were enrolled. MF with the usual dose was administered to all patients for 12 weeks and followed up for 1 year. Clinical evolution was recorded systematically by photographs at screening and at 12 weeks, 6 months, and 12 months after treatment onset. Definitive cure consisted of disappearance of skin lesions with a negative PCR at 12 weeks or with >70% of lesions, disappearing or fading at 12-month follow-up. Patients with reappearing clinical features and any positive diagnostics of PKDL during the follow-up were considered as nonresponsive. Results: Among 300 patients, 286 (95.3%) completed 12 weeks of treatment. The per-protocol cure rate at 12 months was 97%, but 7 patients relapsed and 51 (17%) were lost to 12-month follow-up, resulting in a final cure rate of only 76%. Eye-related adverse events were noted in 11 (3.7%) patients and resolved in most (72.7%) within 12 months. Unfortunately, 3 patients had persistent partial vision loss. Mild to moderate gastrointestinal side effects were seen in 28% patients. Conclusions: Moderate effectiveness of MF was observed in the present study. A significant number of patients developed ocular complications, and thus MF for treatment for PKDL should be suspended and replaced with a safer alternative regimen.

Impact of switching prophylaxis treatment from factor VIII to emicizumab in hemophilia A patients without inhibitors.

BACKGROUND: Factor VIII (FVIII) replacement and emicizumab are effective at preventing bleeds in patients with hemophilia A (HA). Though benefits of emicizumab among inhibitor patients with HA (PwHA) are well established, more real-world evidence among non-inhibitor patients is needed. METHODS: Using a United States healthcare claims database, we compared billed annualized bleed rates (ABRb) and the total cost of care (TCC) before and after switching from FVIII prophylaxis to emicizumab among non-inhibitor male PwHA. Bayesian inferences were used to assess the difference in ABRb and TCC per patient per year (PPPY) pre- versus post-prophylaxis switch. RESULTS: We included 101 non-inhibitor male PwHA aged between 3 and 63 years old who switched from FVIII prophylaxis to emicizumab prophylaxis in 2018 or 2019. The ABRb increased from 0.52 to 0.62 (p = 0.83) after switch. The posterior probability of the mean ABRb increasing after the switch was 75.54%. The TCC PPPY increased from $517,143 to $627,005 (p < 0.0001) after switch and the posterior probability of mean costs increasing after the switch was 99.80%. CONCLUSIONS: Personalization of care through the identification of the most appropriate therapy for each patient can optimize clinical and economic outcomes. Future real-world evidence research could help establish the value of prophylactic options in targeted populations such as the non-inhibitor male PwHA.

Profiling rhythmicity of bile salt hydrolase activity in the gut lumen with a rapid fluorescence assay.

Diurnal rhythmicity of cellular function is key to survival for most organisms on Earth. Many circadian functions are driven by the brain, but regulation of a separate set of peripheral rhythms remains poorly understood. The gut microbiome is a potential candidate for regulation of host peripheral rhythms, and this study sought to specifically examine the process of microbial bile salt biotransformation. To enable this work, an assay for bile salt hydrolase (BSH) that could work with small quantities of stool samples was necessary. Using a turn-on fluorescence probe, we developed a rapid and inexpensive assay to detect BSH enzyme activity with concentrations as low as 6-25 µM, which is considerably more robust than prior approaches. We successfully applied this rhodamine-based assay to detect BSH activity in a wide range of biological samples such as recombinant protein, whole cells, fecal samples, and gut lumen content from mice. We were able to detect significant BSH activity in small amounts of mouse fecal/gut content (20-50 mg) within 2 h, which illustrates its potential for use in various biological/clinical applications. Using this assay, we investigated the diurnal fluctuations of BSH activity in the large intestine of mice. By using time restricted feeding conditions, we provided direct evidence of 24 h rhythmicity in microbiome BSH activity levels and showed that this rhythmicity is influenced by feeding patterns. Our novel function-centric approach has potential to aid in the discovery of therapeutic, diet, or lifestyle interventions for correction of circadian perturbations linked to bile metabolism.

Utility of morphologic assessment of bone marrow biopsy in diagnosis of lysosomal storage disorders.

Introduction: Lysosomal storage disorders (LSDs) are rare disorders and pose a diagnostic challenge for clinicians owing to their generalized symptomatology. In this study, we aim to classify LSDs into two broad categories, namely, Gaucher disease (GD) and Niemann-Pick/Niemann-Pick-like diseases (NP/NP-like diseases) based on the morphology of the storage cells in the bone marrow (BM) aspiration smears and trephine biopsy sections. Materials and Method: This retrospective study includes 32 BM specimens morphologically diagnosed as LSDs at our institute, in the last 10 years. Subsequently, they were subclassified into GD and NP/NP-like diseases. Further, we have compared and analyzed the clinical, hematological, and biochemical parameters for the two groups of LSDs. Results: Based on BM morphology, 59.4% (n = 19) cases were diagnosed as NP/NP-like diseases and 40.6% (n = 13) cases as GD. Abdominal distension and failure to thrive were the most common clinical manifestations in both groups of LSDs. Anemia and thrombocytopenia were frequently seen in either of the LSDs. On the assessment of metabolic profile, elevated total/direct bilirubin and liver enzymes were more commonly seen in NP/NP-like diseases when compared with GD. Conclusion: We have classified LSDs into GD and NP/NP-like diseases based on the morphology of the storage cells in the BM specimen. The hallmark findings on BM biopsy annexed with the comparative features of the two proposed categories can aid the clinician in clinching the diagnosis. Formulation of such a methodology will prove instrumental for patient care in an underresourced setting.

Application of Value Framework to Phase III Trials of Immune Checkpoint Inhibitors in Esophageal and Gastric Cancer.

BACKGROUND: Recent trials testing immune-checkpoint inhibitors in esophago-gastric malignancies have shown mixed results. We aim to assess key subgroups using the ASCO Net Health Benefit Score (NHBS) and ESMO Magnitude of Clinical Benefit Scale (MCBS). MATERIALS AND METHODS: A search for phase III trials of FDA-approved anti-PD-1 or anti-PD-L1 drugs in esophago-gastric cancer trials was identified using www.clinicaltrials.gov. These published studies were scored using the ASCO NHBS and ESMO MCBS. The ASCO NHBS scores were compared by primary site of cancer (esophageal vs gastric) and PD-L1 expression using the Mann-Whitney test and the ESMO-MCBS grading, by Fisher's Exact test. RESULTS: Fifteen of 45 clinical trials were included. Of them, 6 were primarily esophageal cancer trials, and 9 were primarily gastric cancer trials. Ten stratified their analysis based on PD-L1 expression. The ASCO NHBS score was higher (mean 40, range 20 to 56.6 vs. mean 12, range -1.1 to 18.4, P < .01) for esophageal cancer than gastric cancer. No difference was observed in survival and response endpoints between the 2 groups. Similarly, the ESMO MCBS scored higher for esophageal cancer group than gastric cancer (P < .05). Additionally, the scores were higher in those with high PD-L1 expression vs. low PD-L1 (mean 36, range 11.2-66.6 vs. mean 14, range -19.5 to 43.6, P < .05). CONCLUSION: The ASCO NHB and ESMO scores were consistently higher among esophageal cancer trials than gastric cancer trials and in those with high PD-L1 expression than low expression. Histology and PD-L1 expression should be considered when discussing value of immunotherapy to patients.

Red cell alloimmunization in pregnancy: a study from a premier tertiary care centre of Western India.

OBJECTIVE: The study was conducted to determine the frequency of alloimmunization to various blood group antibodies in pregnant women, and the risk of hemolytic disease in the fetus and newborn. METHODS: All antenatal women, irrespective of the period of gestation or obstetric history, were included, whereas those taking anti-D immune-prophylaxis or with a history of blood transfusion were excluded. Antibody screening and identification were performed using a Bio-Rad ID microtyping system. RESULTS: Of 2,084 antenatal females, 1,765 were D-antigen positive and 319 D-antigen negative. Sixty-five (3.119%) women alloimmunized. Out of 54 (2.591%) who had sensitized to D-antigen, 11 (0.527%) also sensitized to other antibodies. These 11 alloantibodies identified included: anti-M (n=6; 9.23%), anti-C (n=1; 3.076%), anti-E (n=1; 1.538%), anti-e (n=1; 1.538%), anti-Lewis (a) (n=1; 1.538%), and unspecified antibodies (n=1; 1.538%). Multiple antibodies were seen in four patients that combined: anti-D and anti-C (n=2; 3.076%), anti-e and anti-c (n=1; 1.538%), and anti-D and anti-G (n=1; 1.538%). CONCLUSION: The rate of alloimmunization in D-antigen-negative women was high. Apart from this, the alloimmunization rate in women with bad obstetric history was very high, at 8.1%. In developing countries such as India, universal antenatal antibody screening, though desirable, may not be justified at present, as the cost and infrastructure required would be immense because of the lower alloimmunization rates in RhD antigen-positive women. However, it is necessary to impose properly formulated protocols to screen pregnant women with bad obstetric history.

Ileo-dermoid Fistula: A Rare Presentation of Ovarian Dermoid.

Mature cystic teratoma is a benign ovarian tumor that usually presents in reproductive-age females. This tumor usually presents with pain abdomen, bloating, and a lump. Hereby, we describe a case of an ovarian dermoid presented with features of intestinal obstruction secondary to ileo-dermoid fistula formation. A 55-year-old postmenopausal female presented with lower abdominal pain, nausea, vomiting, and the feeling of a lump in the abdomen. On evaluation and imaging, it was diagnosed as a large ovarian dermoid (with malignant transformation) with multiple fistulous communications with ileal loops. The patient was managed by laparotomy, total abdominal hysterectomy with bilateral salpingo-oophorectomy, bowel resection, and anastomosis. The patient was discharged in good condition. The rupture of malignant ovarian dermoid followed by enterodermoid fistula formation and intestinal obstruction is rare. Complete cytoreduction and bowel repair should be considered for optimal results.

Identifying the Potential Determinants of Tobacco Counseling Implementation among Oral Health Professionals of India: A Cross-Sectional Survey

ABSTRACT Objective: To identify the potential determinants of tobacco counseling implementation among oral health professionals in India. Material and Methods: A cross-sectional survey was carried out among the 298 dentists of Aligarh and Gwalior. The questionnaire used in the study had sections on dentists' sociodemographic data and a 35-item questionnaire to assess the potential determinants of tobacco cessation counseling. Descriptive statistics were carried out, and a Chi-square test was utilized to determine the association. P-value <0.05 was considered statistically significant. Results: Domains "knowledge", "Professional Responsibility and Identity", and "Remembrance, awareness, and judgment" showed a statistically significant correlation with most tobacco cessation counseling behaviors. In addition, undergraduate education received in Tobacco Cessation counseling, and Continuing education received in Tobacco Cessation counseling had significantly impacted the practice of tobacco cessation counseling (p=0.02 and 0.04, respectively). Conclusion: This study suggests that "Knowledge", "Professional Responsibility and Identity" and "Remembrance, awareness, and judgment" are the potential determinants that could be used to design effective strategies to enhance tobacco counseling among dentists in India.

A Comparative Study to Evaluate the Anesthetic Efficacy of Buffered Versus Non-buffered 2% Lidocaine During Inferior Alveolar Nerve Block.

BACKGROUND: The study aimed to compare the clinical efficacy, safety, and acceptability of buffered lidocaine (8.4% sodium bicarbonate and 2% lidocaine with 1:80,000 adrenaline) versus non-buffered lidocaine (2% lidocaine with 1:80,000 adrenaline) during inferior alveolar nerve block. MATERIALS AND METHODS: Fifty patients who required bilateral extractions in a single arch were included in this study. One hundred extractions were carried out, and all of the patients had nerve blocks during the procedure. We also took note of the patient's pain level as measured on a visual analog scale, as well as the start of the action, duration of postoperative analgesia, and occurrence of any problems. The duration of anesthesia was assessed by the feeling of numbness and the first sign of pain. RESULT: All the patients in both study groups reported subjective numbness of the lips and tongue. The depth of anesthesia was evaluated by pain and comfort during the procedure with a visual analog scale and showed no significant difference between the two groups. The onset of action for the pterygomandibular nerve block was 1.240.31 minutes (buffered) and 1.710.51 minutes (non-buffered). When compared, the duration of anesthesia was 327.18102.98 minutes (buffered) and 129.0826.85 minutes (non-buffered). CONCLUSION: This study concludes that the buffered solution has a faster onset of action than the non-buffered solution. Both solutions exhibit similar intraoperative efficacy. The duration of postoperative anesthesia was prolonged with buffering. Buffering also reduced pain scores during the early postoperative period.

Evaluation of The Sealing Ability of Gutta Percha with Bioroot RCS, MTA Fillapex and Sealapex - An SEM Study.

Aim of the Study: The objective of this in-vitro study was to assess the screening capabilities of three endodontic sealers, namely the BioRoot RCS, the MTA Fillapex, and Sealapex (a calcium hydroxide-based sealer), and the gutta-percha cone by using a scanning electron microscopy to the dentine walls. The results from the research are presented here. Results: ZOE exhibited more gaps in the sealing materials evaluated with the least dental sealing performance, followed by the cervical third by the MTA Fillapex, the Sealapex, and the BioRoot RCS. The ZOE, followed by Sealapex, MTA Fillapex, and BioRoot RCS, exhibited inadequate dental wall sealing capacity in the middle of the third. The third apical ZOE exhibited more deficiencies in the formation of dental walls, followed by Sealapex, MTA Fillapex, and BioRoot RCS. Conclusion: Under the constraints of the investigation, it can be stated that for the bioceramic sealer, a minimal gap was seen, with RCS of BioRoot superior to Fillapex of MTA. In the middle third, Sealapex was better adapted to the calcium hydroxide-based sealant than the MTA Fillapex sealer. MTA Filllapex had lower gap development than Sealapex in cervical or apical thirds.

A real-world study comparing pre-post billed annualized bleed rates and total cost of care among non-inhibitor patients with hemophilia A switching from FVIII prophylaxis to emicizumab.

OBJECTIVE: Factor VIII (FVIII) replacement and emicizumab have demonstrated efficacy for prevention of bleeds among patients with hemophilia A (PwHA) compared to on-demand (OD) use. Evidence investigating clinical outcomes and healthcare costs of non-inhibitor PwHA switching from prophylaxis with FVIII concentrates to emicizumab has not been well-established within large real-world datasets. This study aimed to investigate billed annualized bleed rates (ABRb) and total cost of care (TCC) among non-inhibitor PwHA switching from FVIII-prophylaxis to emicizumab-prophylaxis. METHODS: This retrospective, observational study was conducted using IQVIA PharMetrics Plus, a US administrative claims database. The date of first claim for emicizumab was defined as the index date. OD patients and inhibitor patients were excluded. Bleeds were identified using a list of 535 diagnosis codes. Bayesian models were developed to estimate the probability ABRb worsens and TCC increases after switching to emicizumab. Wilcoxon rank-sum tests were used to test statistical significance of changes in ABRb and TCC after switch. RESULTS: Among the 121 identified patients, the difference in mean ABRb between FVIII-prophylaxis (0.68 [SD = 1.28]) and emicizumab (0.55 [SD = 1.48]) was insignificant (p = .142). The mean annual TCC significantly increased for patients switching from FVIII-prophylaxis ($518,151 [SD = $289,934]) to emicizumab ($652,679 [SD = $340,126]; p < .0001). The Bayesian models estimated a 21.0% probability of the ABRb worsening and a 99.9% probability of increasing TCC after switch. CONCLUSIONS: This study found that in male non-inhibitor PwHA, switching from FVIII prophylaxis to emicizumab incurs substantial cost increase with no significant benefit in ABRb. This evidence may help guide providers, payers, and patients in shared decision-making conversations around best treatment options.