Apalutamide-Induced Toxic Epidermal Necrolysis in a Caucasian Patient with Metastatic Castration-Sensitive Prostate Cancer: A Case Report and Review of the Literature.

Apalutamide is a novel nonsteroidal androgen receptor inhibitor that has been shown to improve outcomes for patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer when combined with androgen deprivation therapy. Apalutamide-induced skin rash occurred commonly in clinical trials, with 23.8-27.1% of patients experiencing a rash of any grade, and 5.2-6.3% experiencing a rash of grade three or higher. There were no cases of severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) reported in clinical trials; however, there are rare cases reported in the literature with the majority occurring in Asian patients. An 83-year-old Caucasian male was commenced on apalutamide, combined with degarelix, for the management of metastatic castration-sensitive prostate cancer. During week five of apalutamide treatment, the patient developed a widespread erythematous maculopapular rash. On presentation, the rash affected 80% of his body surface area (BSA) and a diagnosis of a severe cutaneous drug eruption was made. He was commenced on methylprednisolone (MP) therapy. Despite 5 days of MP, the rash continued to deteriorate involving 95% of his BSA. Nikolsky's sign was positive. A diagnosis of overlap SJS/TEN was made, supported by skin biopsy. His SCORTEN score was three. He was then commenced on intravenous immunoglobulin and transferred to the intensive care unit. Over the coming days, the rash began to stabilise, and his steroid dose was weaned. He was discharged from hospital 38 days after rash onset. We report the first suggested case of apalutamide-induced SJS/TEN in a Caucasian patient. We discuss other cases of apalutamide-induced SCARs reported in the literature. Risk factors seem to include low body weight and Japanese race, as well as short time to onset of rash.

Global Rural and Remote Patients With Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE: Rural and remote patients with rheumatoid arthritis (RA) are at risk for inequities in health outcomes based on differences in physical environments and health care access potential compared to urban populations. The aim of this systematic review was to synthesize epidemiology, clinical outcomes, and health service use reported for global populations with RA residing in rural and remote locations. METHODS: Medline, Embase, HealthStar, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library were searched from inception to June 2019 using librarian-developed search terms for RA and rural and remote populations. Peer-reviewed published manuscripts were included if they reported on epidemiologic, clinical, or health service use outcomes. RESULTS: Fifty-four articles were included for data synthesis, representing studies from all continents. In 11 studies in which there was an appropriate urban population comparator, rural and remote populations were not at increased risk for RA; 1 study reported increased prevalence, and 5 studies reported decreased prevalence in rural and remote populations. Clinical characteristics of rural and remote populations in studies with an appropriate urban comparator showed no significant differences in disease activity measures or disability, but 1 study reported worse physical function and health-related quality of life in rural and remote populations. Studies reporting on health service use provided evidence that rural and remote residence adversely impacts diagnostic time, ongoing follow-up, access to RA-care-related practitioners and services, and variation in medication access and use, with prominent heterogeneity noted between countries. CONCLUSION: RA epidemiology and clinical outcomes are not necessarily different between rural/remote and urban populations within countries. Rural and remote patients face greater barriers to care, which increases the risk for inequities in outcomes.

T Scores, FRAX, Frailty Phenotype, Falls, and Its Relationship to Fractures in Patients on Maintenance Hemodialysis.

BACKGROUND: Despite the magnitude of fracture and the consequences in patients receiving hemodialysis, optimal risk assessment tools in this population are not well explored. Frailty and falls-known risk factors for fracture in chronic kidney disease (CKD) and non-CKD populations-are common in patients receiving hemodialysis (HD) therapy. While the relationship between T scores in relation to fractures in patients receiving HD is recognized, there is a paucity of data to the additional contributions of fracture assessment tool (FRAX), frailty status, and falls in its relationship with fracture. OBJECTIVES: To evaluate the clinical utility of adding FRAX, frailty status, and falls to T scores at the femoral neck to determine whether it enhances fracture discrimination in patients on maintenance HD. DESIGN: A cross-sectional observational study. SETTING: Two main dialysis units in Regina, Saskatchewan, Canada. PATIENTS: A total of 109 patients on maintenance HD at two dialysis units from January 1, 2017, to December 31, 2018, were included in the study. MEASUREMENTS: Fracture (the main outcome) was documented based on the review of medical charts, self-recall, and additionally vertebral fractures were identified by an x-ray. Areal bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). FRAX score was calculated using an online algorithm based on 11 clinical risk factors. We calculated the FRAX score for hip fracture and major osteoprotoic fracture with and without the inclusion of BMD. Frailty was assessed using the Fried criteria, which included assessments of unintentional weight loss, weakness (handgrip strength), slowness (walking speed), and questionnaires for physical activity and self-perceived exhaustion. Patients were enquired about the history and frequency of falls. METHODS: A total of 131 patients underwent frailty assessments at the two dialysis units during the dialysis treatment. Following frailty assessments, they were referred for DXA scans and upon receipt of the results undertook FRAX questionnaires. They were additionally sent for lumbar x-rays and contacted for a history of falls. Association between the BMD-T score, FRAX, frailty status, falls, with fracture were examined with sequential multivariable logistic regression models. Differences were considered statistically significant at P values <.05. RESULTS: A total of 109 patients were included in the data analysis. The composite of fracture occurred in 37.6% of patients. About 59.3% were identified as frail, and 29% of the participants had at least one fall in the last year. On multivariate regression analysis, each lower standard deviation (SD) in femoral neck T score was associated with 48% higher odds of fracture (odds ratio [OR] = 1.48; 95% confidence interval [CI] 1.20-1.68, P = .005). With the inclusion for FRAX scores (hip), the OR for fracture remained significant at 1.38 (OR = 1.38, 95% CI 1.04-1.63, P = .043). The addition of frailty status and history of falls did not further improve the model. Low T score and FRAX were both independent risk factors in patients on HD therapy. LIMITATIONS: This is a single-center study with a small sample size which limits the generalizability of the findings. Due to the cross-sectional study, associations identified may be difficult to interpret. CONCLUSIONS: Both BMD measurements by DXA and FRAX are useful tools to assess fracture in patients receiving HD. The addition of frailty status and history of falls is not associated with fractures in this population. Larger prospective studies are needed to determine whether the inclusion of frailty and falls to the conventional models will improve fracture assessment in the population receiving HD. TRIAL REGISTRATION: The study was not registered on a publicly accessible registry as it did not involve health care intervention on human participants.

CONTEXTE: Les outils permettant une évaluation optimale du risque de fractures chez les patients hémodialysés demeurent sous-examinés malgré le nombre de fractures et leurs conséquences dans cette population. La fragilité et les chutes ­ des facteurs de risque connus de fracture chez les patients atteints ou non d'insuffisance rénale chronique (IRC) ­ sont fréquentes chez les patients hémodialysés. Bien qu'un lien entre les scores T et les fractures soit reconnu chez les patients hémodialysés, très peu de données existent sur les contributions supplémentaires de l'outil d'évaluation des fractures (FRAX), de l'état de fragilité des patients et des antécédents de chutes dans leur lien avec les fractures. OBJECTIF: Évaluer l'utilité clinique d'ajouter le FRAX, l'état de fragilité et les chutes aux scores T du col fémoral pour déterminer s'ils améliorent la discrimination des fractures chez les patients suivant des traitements d'hémodialyse d'entretien. TYPE D'ÉTUDE: Étude transversale et observationnelle. CADRE: Les deux principales unités de dialyse de Régina (Saskatchewan) au Canada. SUJETS: Ont été inclus 109 patients suivant des traitements d'hémodialyse d'entretien dans les deux unités de dialyse entre le 1er janvier 2017 et le 31 décembre 2018. MESURES: L'auto-rappel et l'examen du dossier médical ont permis de documenter les fractures (principal résultat); les fractures vertébrales ont été confirmées par radiographie. La densité minérale osseuse (DMO) de surface a été mesurée par absorptiométrie double énergie à rayons X (DEXA). Le score FRAX a été calculé avec un algorithme en ligne selon 11 facteurs de risque cliniques. Le score FRAX pour les fractures de la hanche a été calculé avec et sans la DMO. La fragilité a été évaluée selon les critères de Fried, lesquels comprenaient l'évaluation d'une perte de poids involontaire, de la faiblesse (force de préhension) et de la lenteur (vitesse de marche), et à l'aide d'un questionnaire évaluant l'activité physique et le niveau d'épuisement perçu. Les patients ont été questionnés sur leurs antécédents de chutes et sur leur fréquence. MÉTHODOLOGIE: Au total, dans les deux unités de dialyse, 131 patients ont subi une évaluation de la fragilité pendant leurs traitements. Après l'évaluation, les patients ont été aiguillés pour un examen par DEXA et, à la réception des résultats, ont répondu à des questionnaires FRAX. Ils ont également passé une radiographie lombaire et ont été contactés pour discuter de leurs antécédents de chutes. L'association entre une fracture et le score BMD-T, le FRAX, l'état de fragilité et les chutes a été examinée à l'aide de modèles séquentiels de régression logistique multivariée. Les différences ont été considérées comme statistiquement significatives à des valeurs de P supérieures à 0,05. RÉSULTATS: L'analyse porte sur un total de 109 patients. Un critère combiné associant une fracture était présent chez 37,6 % des sujets; 59,3 % des patients ont été jugés fragiles et 29 % avaient chuté au moins une fois au cours de la dernière année. Dans l'analyse de régression multivariée, chaque valeur inférieure d'écart-type (É-T) pour le score T du col fémoral a été associée à un risque 48 % plus élevé de fracture (rapport de cote [RC] = 1,48; IC à 95 %: 1,20-1,68; P = 0,005). En incluant les scores FRAX (hanche), le rapport de cote pour la fracture est demeuré significatif à 1,38 (RC = 1,38; IC à 95 %: 1,04-1,63; P = 0,043). L'ajout de l'état de fragilité et des antécédents de chutes n'a pas amélioré le modèle. Un faible score T et un faible score FRAX se sont tous deux avérés un facteur de risque indépendant chez les patients hémodialysés. LIMITES: L'étude est monocentrique et l'échantillon est de faible taille, ce qui limite la généralisation des résultats. Les associations identifiées peuvent être difficiles à interpréter en raison de la nature transversale de l'étude. CONCLUSION: Les mesures de la DMO, qu'elles soient faites par DEXA ou par FRAX, sont des outils utiles pour évaluer les fractures chez les patients hémodialysés. L'ajout de l'état de fragilité et des antécédents de chutes n'a pas été associé aux fractures dans cette population. Des études prospectives de plus grande envergure sont nécessaires pour déterminer si l'inclusion de l'état de fragilité et des antécédents de chutes dans les modèles classiques améliorerait l'évaluation des fractures chez les patients hémodialysés. ENREGISTREMENT DE L'ESSAI: L'étude n'a pas été inscrite dans un registre accessible au public puisqu'elle n'implique aucune intervention sur les participants.

Peritoneal Dialysis Exit Site Pyoderma Gangrenosum: A Case Report.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare, chronic inflammatory condition exhibiting mucopurulent or hemorrhagic exudates. The majority of cases are associated with inflammatory bowel disease, rheumatological diseases, and hematological malignancies. In the absence of typical serological markers and specific histopathological changes, the diagnosis is often clinical. Being rare, it is frequently misdiagnosed, which leads to a delay in instituting appropriate therapy. CASE PRESENTATION: We present a 53-year-old male of Aboriginal descent with end-stage renal disease due to diabetes who underwent insertion of a peritoneal dialysis (PD) catheter. Five weeks after PD catheter insertion, he started to notice a painful ulcer surrounded by a bed of erythema. The lesion eventually progressed to a purulent, hemorrhagic ulcer surrounded by a raised, irregular, violaceous border along the entirety of the PD catheter tunnel. There was no history of underlying systemic diseases commonly associated with PG. The catheter was removed, and an elliptical biopsy was taken, which ruled out infection, malignancy, and vasculitis. The changes were felt to be consistent with PG. The patient underwent treatment initially with topical corticosteroids, followed by oral prednisone, which unfortunately worsened his diabetic control; due to this, he was transitioned to cyclosporine, with complete resolution. CONCLUSIONS: Lesions at the PD catheter exit site are usually treated for infections. However, for ulcers that are painful, rapidly expanding, nonhealing, and unresponsive to antibiotics, PG should be considered as a differential diagnosis. This is the first reported case of PG occurring at the exit site of a PD catheter.

How familiar are our doctors towards Rabies prophylaxis- A study from coastal south India.

BACKGROUND: Rabies, a 100% fatal disease claims more than 59,000 human lives every year globally. One human life is lost every 15 minutes due to this deadly preventable disease. Timely initiation of post exposure prophylaxis following an animal exposure can result in 100% preventability of this fatal disease. METHODOLOGY: This facility based study was conducted among clinical fraternities of teaching hospitals. A semi structured questionnaire was used for collection of data. Institutional Ethics Committee approval was sought. The study investigators visited the workplace of the participants and distributed the questionnaire. SPSS Ver 16 (Chicago, IL, USA) was used to analyse the data. FINDINGS: Most of the participants knew that veterinary groups and zoo-keepers should be given pre-exposure prophylaxis. Many participants knew about the Intra Muscular schedule of anti-rabies vaccine and its site of administration for pre exposure prophylaxis. It was observed that most participants had knowledge regarding correct intramuscular regimen of anti-rabies vaccine for post-exposure prophylaxis but less than half were able to differentiate between the intramuscular and intradermal regimens. Less than half of participants were aware of the fact that local administration of anti-rabies serum is useful. CONCLUSION: The knowledge regarding WHO categorisation of animal exposure and recommended post exposure prophylaxis according to type of exposure observed to be minimal among clinical fraternity.