Withdrawal Of Treatment Research Articles

Phase II study of atezolizumab and bevacizumab combination therapy for patients with advanced hepatocellular carcinoma who previously received systemic treatment.

495 Background: Atezolizumab plus bevacizumab (AteBev) has been established as a standard of care for patients with untreated advanced hepatocellular carcinoma (HCC). Lenvatinib was once the first choice and remains a treatment option for such patients; however, no subsequent treatment to date has proven a similar level of efficacy. This study aimed to evaluate the efficacy of AteBev in patients with HCC previously treated with lenvatinib. Methods: In this single-center, open-labeled, single-arm, phase II study, patients with advanced HCC previously treated with at least one systemic treatment were enrolled to receive 1,200 mg of atezolizumab and 15 mg/kg of bevacizumab intravenously every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, tumor control rate, and frequency of adverse events. The threshold and expected PFS were 3 months and 6.8 months, respectively, at a one-sided significance level of 0.05, and statistical power of 80%. Based on these data, the number of patients required was estimated to be 26. Results: Among 29 patients enrolled between November 2020 and October 2022, 26 previously treated with lenvatinib were included in the primary efficacy analysis. Median PFS was 9.70 [90% confidence interval (CI), 5.10–14.24] months. Median overall survival was 17.23 (90% CI, 3.18–27.85) months, and response rate and tumor control rate were 34.6% and 69.2%, respectively. Severe adverse events were observed in six patients (23.1%), six patients (23.1%) discontinued treatment because of immune-related adverse events or treatment-refractory ascites, and 10 patients (38.5%) required the withdrawal of treatment mainly because of proteinuria. There were no treatment-related deaths. Conclusions: AteBev for patients with advanced HCC previously treated with lenvatinib had a comparable efficacy to that in patients with no prior treatment. It may therefore be a treatment option for patients with advanced HCC previously treated with lenvatinib. Clinical trial information: jRCT1041200068 .

Real-world outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma in Japanese patients: data with a minimum of 3years of follow-up.

Long-term follow-up data regarding treatment outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma as a first-line therapy are limited in real-world Japanese populations. We retrospectively evaluated data of 56 advanced renal cell carcinoma patients treated with nivolumab plus ipilimumab, with a follow-up of at least 3years. Survival, tumour response and adverse event profiles were assessed. A total of 41 patients (73%) were histopathologically diagnosed with clear-cell renal cell carcinoma, and 34 (61%) were categorized into the International Metastatic renal cell carcinoma Database Consortium intermediate-risk group. The median follow-up period was 34.4months. Regarding an effectiveness profile, median progression-free survival, time to treatment failure and overall survival were 9.01, 12.5 and 49.0months, respectively. Objective response was observed in 27 patients (48%), including eight patients with complete response (14%), and the median duration of response was 30.8months. Multivariate analyses showed that clear-cell histology was an independent factor of longer overall survival (hazard ratio: 0.23, P=0.0013). Regarding safety profiles, adverse events of any grade and those with grade≥3 developed in 40 (71%) and 25 patients (45%), respectively. Median time to adverse event development was 1.68months. Treatment was interrupted in 28 patients (50%), and corticosteroid administration was needed in 25 (45%). The 3-year follow-up data showed that nivolumab plus ipilimumab combination therapy exhibited a feasible effectiveness in real-world Japanese patients with advanced renal cell carcinoma. Accordingly, the high risk of adverse event development, which often requires treatment withdrawal and corticosteroid administration, should be considered.

Attrition from Face-to-Face Pediatric Outpatient Chronic Pain Interventions: A Narrative Review and Theoretical Model.

There is limited understanding of attrition (premature treatment withdrawal and non-completion) from pediatric chronic pain services. This narrative review aimed to summarize attrition prevalence from face-to-face pediatric outpatient chronic pain interventions, identify associated factors and develop a theoretical model to account for attrition in this setting. A comprehensive search of the published literature revealed massive variability (0-100%) in the reported attrition rates from pediatric chronic pain interventions that varied in type and format (individual vs. group, single discipline vs. interdisciplinary, psychological only vs. multiple combined interventions, of different durations). The factors associated with attrition from pediatric chronic pain programs varied between the studies: some have assessed patient sex, psychological and other comorbidities, avoidance strategies, missed schooling, family composition/tensions, caregiver catastrophizing, scheduling, caregiver leave and clinic access. A theoretical model is presented depicting youth, caregiver and service factors that may impact attrition from pediatric chronic pain interventions. Where available, literature is drawn from the pediatric chronic pain context, but also from adult chronic pain and pediatric weight management fields. The implications for research and clinical practice are discussed, including improved reporting, patient screening and targeted supports to promote intervention completion. This review contributes to a better understanding of attrition, which is crucial for optimizing pediatric chronic pain service outcomes.

Ixekizumab-induced urticaria is associated with the short duration of remission in psoriasis by activation of mast cells

BackgroundMast cell degranulation plays a pivotal role in urticaria and is also an early histological characteristic of psoriasis. However, whether the activation of mast cells contributes to psoriasis recurrence after discontinuation of IL-17A blockers remains unclear. ObjectiveTo investigate the role of mast cells in ixekizumab treatment-associated urticaria (ITAUR) and assess the effect of urticaria eruption on psoriasis relapse. MethodsA retrospective analysis was performed on biopsies of patients who experienced psoriasis relapse after discontinuation of ixekizumab. Transcriptomic and histopathological features were assessed. Patterns were compared between patients with ITAUR and non-urticaria (NUR) as well as psoriasis-like mice with mast cell activation or inactivation. ResultsPatients with ITAUR experienced early relapse compared to NUR group after treatment withdrawal. Transcriptomic and histopathological analyses revealed that patients with ITAUR had an elevated proportion of mast cells in resolved skin. Especially, the proportion of IL-17A-positive mast cells was inversely correlated with the duration of remission. LimitationsThe mechanism of mast cell activation in ITAUR has not been precisely elucidated. ConclusionIxekizumab treatment increases IL-17A-positive mast cells in lesions of ITAUR, which is associated with early psoriasis relapse after ixekizumab withdrawal.

Parents' experiences of palliative care decision-making in neonatal intensive care units: An interpretative phenomenological analysis.

This work explores the experiences and meaning attributed by parents who underwent the decision-making process of withholding and/or withdrawing life-sustaining treatment for their newborn. Audio-recorded face-to-face interviews were led and analysed using interpretative phenomenological analysis. Eight families (seven mothers and five fathers) whose baby underwent withholding and/or withdrawing of life-sustaining treatment in three neonatal intensive care units from two regions in France were included. The findings reveal two paradoxes within the meaning-making process of parents: role ambivalence and choice ambiguity. We contend that these paradoxes, along with the need to mitigate uncertainty, form protective psychological mechanisms that enable parents to cope with the decision, maintain their parental identity and prevent decisional regret. Role ambivalence and choice ambiguity should be considered when shared decision-making in the neonatal intensive care unit. Recognising and addressing these paradoxical beliefs is essential for informing parent support practices and professional recommendations, as well as add to ethical discussions pertaining to parental autonomy and physicians' rapport to uncertainty.

Technology-Assisted Parenting Intervention Plus Therapist Coaching: A Pilot Randomized Trial in a Community Practice Setting

ABSTRACT Disruptive behaviors are the most common clinical presentation in children and adolescents, particularly among disadvantaged youth referred to community mental health clinics (CMHCs). When left unaddressed, disruptive behaviors can increase the risk of adverse mental health outcomes. While parenting interventions are known to be efficacious and efficient treatment approaches, there are many barriers to involvement in such programs, particularly for disadvantaged populations. This pilot randomized controlled trial evaluated a technology-assisted parenting intervention (Parenting Wisely, PW) with therapist coaching compared to treatment as usual (TAU) at a CMHC. Participants included 53 caregiver-adolescent dyads and 13 clinicians recruited from a CMHC. Dyads randomized to PW + therapist coaching received a multi-component intervention that utilized a technology-assisted parenting program alongside therapist coaching sessions. Feasibility/acceptability assessments were conducted and preliminary findings on parenting outcomes and adolescent behavior outcomes were collected at 3- and 6-months post-baseline. Qualitative and quantitative results supported the feasibility and acceptability of the parenting PW + therapist coaching intervention as evidenced by caregiver engagement, therapist adherence, lack of treatment withdrawals, and satisfaction ratings. Exploratory analyses did not show differences between treatment conditions for parenting and adolescent behavioral outcomes. PW + therapist coaching may be better suited for early adolescents, who are at a critical period when disruptive behavior patterns are not yet ingrained, and parents have more authority and opportunity to address family interactions. Next steps for further evaluation include testing the effectiveness, predictors, moderators, and mechanisms of treatment outcomes of PW + therapist coaching as an adjunct to usual care.

Adverse events of immune checkpoint therapy alone versus when combined with vascular endothelial growth factor inhibitors: a pooled meta-analysis of 1735 patients.

Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone. A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and one arm treated with monotherapy. Adverse event data were pooled using a restricted maximum likelihood fixed effects model, and heterogeneity using Cochran's Q (chi-square) test. 7 out of 9366 studies met the inclusion criteria, and 808 and 927 patients were treated with ICT monotherapy and a combination of ICT with VEGFi, respectively. Only one study reported irAEs, so the analysis was restricted to TRAEs. The total number of TRAEs was significantly higher in the ICT + VEGFi group (RR:1.49; 95% CI 1.37 -1.62; p=1.5×10-21), and more frequent treatment withdrawals were attributed to TRAEs (RR:3.10; 95% CI 1.12-8.59; p=0.029). The highest TRAE effect size increases noted for rash (RR 6.50; 95% CI 3.76 - 11.25; p=2.1×10-11), hypertension (RR:6.07; 95% CI 3.69-10.00; p=1.3×10-12), hypothyroidism (RR:5.02; 95% CI 3.08 - 8.19; p=8.9×10-11), and diarrhea (RR:4.94; 95% CI 3.21-7.62; p=3.8×10-13). Other significantly more frequent TRAEs included nausea, anemia, anorexia, and proteinuria. Combination therapy with ICT and VEGFi carries a higher risk of certain TRAEs, such as rash, hypertension, hypothyroidism, diarrhea, nausea, anorexia, and proteinuria, compared to ICT monotherapy. More granular details on the cause of AEs, particularly irAEs, should be provided in future trials of such regimens.

Euthanasia and End-of-Life Decisions: From the Empirical Turn to Moral Intuitionism.

Most medical learned societies have endorsed both "equivalence" between all forms of withholding or withdrawing treatment and the "discontinuity" between euthanasia and practices to withhold or withdraw treatment. While the latter are morally acceptable insofar as they consist in letting the patient die, the former constitutes an illegitimate act of actively interfering with a patient's life. The moral distinction between killing and letting die has been hotly debated both conceptually and empirically, most notably by experimental philosophers, with inconclusive results. This article employs a "revisionary" intuititionist perspective to discuss the results of a clinical ethics study about intensivists' perceptions of withhold or withdraw decisions. The results show that practitioners' moral experience is at odds with both the discontinuity and equivalence theses. This outcome allows us to revisit certain concepts, such as intention and causal relationship, that are prominent in the conceptual debate. Intensivists also regard end-of-life decisions as being on a scale from least to most active, and whether they regard active forms of end-of-life decisions as ethically acceptable depends on the overarching professional values they endorse: the patient's best chances of survival, or the patient's quality of life.

Опыт лечения больных хронической ВГС‑инфекцией пангенотипной комбинацией препаратов прямого противовирусного действия (глекапревир/пибрентасвир) в Ставропольском крае

Objective. To analyze the results of usage of pangenotype combination glecaprevir/pibrentasvir (GLE/PIB) in real clinical practice in Stavropol Krai within the framework of the regional program on chronic hepatitis C (CHC) treatment. Materials and methods. In the framework of this study, a retrospective analysis of the use of GLE/PIB combination in the period from 2018 to 2022 within the framework of the regional program for the treatment of CHC in the Stavropol region was carried out. The drug was prescribed in accordance with the current label approved in Russia. Patients were observed during the entire period of GLE/PIB therapy and for 12 weeks after treatment completion. Data for analysis were collected from outpatient records and protocols of the “Regional Medical Commission on Diagnosis, Treatment and Drug Supply of Patients with Chronic Viral Hepatitis B and C in Stavropol Krai”. Results. The analysis included 405 patients treated within the framework of the regional program on drug supply of patients with chronic viral hepatitis B and C in the territory of the Stavropol region. The scope of the examination allowed to assess the sustained virologic response 12 weeks after the end of GLE/PIB therapy (SVR12). 92.6% (375/405) of patients had not previously received antiviral therapy. Absence or minimal manifestations of hepatic fibrosis (F0-1) were noted in 50.9% of patients, advanced stage of fibrosis (F3-4 by METAVIR scale) in 34.6%. The distribution by fibrosis stage was as follows: F0 – 21.98% (89/405), F1 – 28.9% (117/405), F2 – 14.6% (59/405), F3 – 13.1% (53/405), F4 (CP-A) – 21.5% (87/405). All patients with liver cirrhosis had compensated stage of the disease – class A according to Child-Pugh. In the study population, genotype (Gt) 3 prevailed, detected in 55.1% (223/405) of patients. Hepatitis C virus (HCV) Gt1 was diagnosed in 29.4% (119/405) of patients. Among them, 16.5% (67/405) of patients had Gt1b, 0.5% (2/405) had Gt1a, and 12.3% (50/405) of patients with Gt1 had no subtype identified. Gt2 was detected in 11.4% of patients (46/405), 3 (0.7%) patients had a genotype other than 1–3, and 14 (3.5%) patients had no HCV genotype determined. 14 (3.6%, 14/405) patients were co-infected with HCV and HIV. 23.5% (95/405) of patients belonged to the age group older than 60 years. The distribution of patients according to the duration of antiviral therapy was as follows: 8 weeks – 89.4% (362/405), 12 weeks – 6.4% (26/405) and 16 weeks – 4,2% (17/405). 405 (100,0%) out of 405 patients achieved SVR12. There were no cases of serious adverse events and treatment withdrawal during antiviral therapy. Conclusion. GLE/PIB has demonstrated high efficacy in patients with different HCV genotypes (including Gt3) and different stages of liver fibrosis (including compensated cirrhosis) in the real-world setting. The SVR12 rate obtained in this analysis is fully consistent with the data of clinical trials and real clinical practice published earlier. Key words: chronic hepatitis C, glecaprevir/pibrentasvir, pangenotypic, real clinical practice

Have serum vitamin D and ferritin a role in predicting the prognosis of autoimmune hepatitis treatment in children?

To investigate whether serum ferritin and vitamin D levels before starting autoimmune hepatitis (AIH) treatment have a role in disease prognosis regarding a therapeutic response. The prospective study included 100 children diagnosed with AIH according to simplified criteria for diagnosis of AIH. They attended the Pediatric Hepatology Department, National Liver Institute, Menoufia University. The patients underwent measurement of liver transaminases before starting AIH treatment after 6 months from starting therapy. They underwent liver biopsy before starting treatment for proper diagnosis, grading, and staging; only 25 cases were compliant and underwent liver biopsy before treatment withdrawal. Serum ferritin and 25 hydroxy vitamin D levels were significantly higher among those with a complete response (1000-3100 ng/ml, 29-48 ng/ml) than a partial response (550-600 ng/ml, 23-28 ng/ml) and non-response (29.28-92.14, 2.16-8.72) (p < 0.001). Our study showed a relation between serum vitamin D before starting AIH treatment, the severity of AIH and response to therapy. This opens a new area of research on the potential use of vitamin D in patients with AIH. Also, hyperferritinemia at the diagnosis can predict the treatment response.

Beyond Legal Boundaries: Public and Clinician Perspectives on Treatment Withdrawal in Infants With Poor Neurological Prognosis.

Despite medical advancements in neonatal survival rates, many children have poor neurological outcomes. Because the law in Korea restricts the withdrawal of life-sustaining treatment to only cases of imminent death, treatment discontinuation may not be an option, even in patients with poor neurological prognosis. This study investigated the opinions of the general population and clinicians regarding life-sustaining treatment withdrawal in such cases using hypothetical scenarios. We conducted a cross-sectional study on the general population and clinicians using a web-based questionnaire. The sample of the general population from an online panel comprised 500 individuals aged 20-69 years selected by quota sampling. The clinician sample comprised 200 clinicians from a tertiary university hospital. We created hypothetical vignettes and questionnaire items to assess attitudes regarding mechanical ventilation withdrawal for an infant at risk of poor neurological prognosis due to birth asphyxia at 2 months and 3 years after the incidence. Overall, 73% of the general population and 74% of clinicians had positive attitudes toward mechanical ventilator withdrawal at 2 months after birth asphyxia. The proportion of positive attitudes toward mechanical ventilator withdrawal was increased in the general population (84%, P < 0.001) and clinicians (80.5%, P = 0.02) at 3 years after birth asphyxia. Religion, spirituality, the presence of a person with a disability in the household, and household income were associated with the attitudes of the general population. In the multivariable logistic regression analysis of the general population, respondents living with a person with a disability or having a disability were more likely to find the withdrawal of the ventilator at 2 months and 3 years after birth asphyxia not permissible. Regarding religion, respondents who identified as Christians were more likely to find the ventilator withdrawal at 2 months after birth asphyxia unacceptable. The general population and clinicians shared the perspective that the decision to withdraw life-sustaining treatment in infants with a poor neurological prognosis should be considered before the end of life. A societal discussion about making decisions centered around the best interest of pediatric patients is warranted.

The Impact of Withdrawing or Withholding of Life-Sustaining Treatment: A Nationwide Case-Control Study Based on Medical Cost Analysis.

This study measured the impact of the Decisions on Life-Sustaining Treatment Act by analyzing medical cost data from the National Health Insurance Service-National Sample Cohort. After identifying the patients who died in 2018 and 2019, the case and control groups were set using the presence of codes for managing the implementation of life-sustaining treatment with propensity score matching. Regarding medical costs, the case group had higher medical costs for all periods before death. The subdivided items of medical costs with significant differences were as follows: consultation, admission, injection, laboratory tests, imaging and radiation therapy, nursing hospital bundled payment, and special equipment. This study is the first analysis carried out to measure the impact of the Decision on Life-Sustaining Treatment Act through a cost analysis and to refute the common expectation that patients who decided to withhold or withdraw life-sustaining treatment would go through fewer unnecessary tests or treatments.

Automated-detection of risky alcohol use prior to surgery using natural language processing.

Preoperative risky alcohol use is one of the most common surgical risk factors. Accurate and early identification of risky alcohol use could enhance surgical safety. Artificial Intelligence-based approaches, such as natural language processing (NLP), provide an innovative method to identify alcohol-related risks from patients' electronic health records (EHR) before surgery. Clinical notes (n = 53,629) from pre-operative patients in a tertiary care facility were analyzed for evidence of risky alcohol use and alcohol use disorder. One hundred of these records were reviewed by experts and labeled for comparison. A rule-based NLP model was built, and we assessed the clinical notes for the entire population. Additionally, we assessed each record for the presence or absence of alcohol-related International Classification of Diseases (ICD) diagnosis codes as an additional comparator. NLP correctly identified 87% of the human-labeled patients classified with risky alcohol use. In contrast, diagnosis codes alone correctly identified only 29% of these patients. In terms of specificity, NLP correctly identified 84% of the non-risky cohort, while diagnosis codes correctly identified 90% of this cohort. In the analysis of the full dataset, the NLP-based approach identified three times more patients with risky alcohol use than ICD codes. NLP, an artificial intelligence-based approach, efficiently and accurately identifies alcohol-related risk in patients' EHRs. This approach could supplement other alcohol screening tools to identify patients in need of intervention, treatment, and/or postoperative withdrawal prophylaxis. Alcohol-related ICD diagnosis had limited utility relative to NLP, which extracts richer information within clinical notes to classify patients.

Лечение хронического гепатита D в Краснодарском крае – опыт реальной практики

Objective. To analyze the results of treatment of patients with chronic hepatitis D (CHD) in Krasnodar Krai in the conditions of real practice using bulevirtide, an HBV/HDV entry inhibitor. Patients and methods. Interim treatment outcomes were studied in 11 patients with CHD, predominantly at the cirrhotic stage (82%), with the presence of portal hypertension (55%), liver failure (n = 3), and hepatocellular carcinoma (n = 2, detected during treatment). Patients received bulevirtide as monotherapy (n = 7) or in combination with peginterferon (n = 4); evaluation periods ranged from 24–96 weeks of treatment. Results. All patients with known baseline HDV RNA level (n = 5) achieved virologic response, HDV RNA level reduction was -1.8 and -5.5 log10 after 24 and 96 weeks of monotherapy, -2.0–4.9 log10 after 24–72 weeks of combined therapy, with aviremia in 1 patient. In patients with unknown baseline HDV RNA level (n = 6) its dynamics during treatment corresponded to virologic response in 4 patients (decrease from -1.5 to -4.0 log10 in the period from 12/24/48 to 72 weeks of monotherapy, with aviremia in 1 patient). Efficacy improved as treatment continued to 72–96 weeks in 5 of 7 patients (4 received monotherapy, 1 received combination therapy). The overall virologic response rate was 82%, aviremia 18%, and biochemical response (ALT level reduction/normalization) 55%/45%, respectively. All patients with liver dysfunction (n = 3) showed virological and biochemical response, including aviremia and ALT normalization (1 and 2 patients, respectively). Treatment was characterized by good tolerability, absence of severe and serious adverse reactions, cases of treatment withdrawal, stability of liver function indices, including cirrhosis with dysfunction. In 1 patient after hepatectomy for HCC there was a temporary deterioration of liver function with the transition of class A to class B according to Child-Pugh, unrelated to treatment. Conclusion. Interim results of HDV treatment in real practice have demonstrated efficacy, safety and good tolerability of bulevirtide in monotherapy or combination therapy, including in patients with liver dysfunction. Further development of an optimal treatment algorithm is necessary, taking into account the results of ongoing studies, in order to improve patient prognosis and achieve cure of HDV infection. Key words: bulevirtide, hepatocellular carcinoma, decompensated cirrhosis, monotherapy, combination therapy, chronic hepatitis D, liver cirrhosis

Modeling Sex-Bias in Anxiety: Pros and Cons of a Larval Zebrafish Model

Anxiety disorders are the most prevalent psychiatric disorders, exhibiting strong female bias. Clinical studies implicate declining estradiol levels in the exacerbation of anxiety symptoms in the premenstrual phase of the menstrual cycle. This study aimed to simulate estradiol fluctuation-linked anxiety behavior in larval zebrafish, using an estradiol treatment withdrawal model. Contrary to model aims, estradiol treatment withdrawal decreased both basal activity and anxiety-like hyperlocomotion (ANOVA main effect of dose, P < 0.0001 and P < 0.01, respectively) in the light/dark transition test. The accuracy of the estradiol washout model was not improved by longer durations of treatment or withdrawal. Basal activity was slightly altered by supraphysiological concentrations of WAY-200070 in the absence of added estradiol. Estrogen receptor (ER) β expression was not upregulated in larvae exposed to physiologically relevant, low concentrations of estradiol. Longer exposure to low concentrations of estradiol increased antioxidant capacity (P < 0.01). In addition, acute exposure to low concentrations of estradiol increased basal activity. Data suggest that in the current models, estradiol-associated altered activity levels were linked to more favorable redox status, rather than reflecting altered anxiety levels. As such, it is recommended that zebrafish larval behavioral analysis be conducted in parallel with mechanistic studies such as redox indicators, for investigations focused on ER signaling.

Testosterone Replacement in Men with Sexual Dysfunction: An Abridged Version of the Cochrane Systematic Review.

To assess the effects of testosterone replacement therapy (TRT) compared to placebo or other medical treatments in men with sexual dysfunction. We performed a comprehensive search with no restrictions on publication language or status up to 29 August 2023. We only included randomized controlled trials (RCTs). We identified 43 studies with 11,419 randomized participants. We found that TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference [MD]: 2.37, 95% confidence interval [CI]: 1.67 to 3.08; I²=0%; 6 RCTs, 2016 participants; moderate-certainty evidence) compared to placebo. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD: -2.31, 95% CI: -3.63 to -1.00; I²=0%; 5 RCTs, 1,030 participants; moderate-certainty evidence) compared to placebo. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio: 0.83, 95% CI: 0.21 to 3.26; I²=0%; 10 RCTs, 3,525 participants; moderate-certainty evidence) compared to placebo. TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or lower urinary tract symptoms. TRT for men with sexual dysfunction showed no difference in erectile function, sexual quality of life, or cardiovascular mortality compared to placebo. Furthermore, it also appears to no difference in treatment withdrawals due to adverse events, prostate-related events, or lower urinary tract symptoms.

Опыт противовирусной терапии хронического гепатита D в Республике Саха (Якутия)

Objective. To analyze the results of antiviral therapy of patients with chronic hepatitis D (CHD) in the Republic of Sakha (Yakutia). Patients and Methods. Interim treatment outcomes over 48 weeks were studied in 36 patients receiving bulevirtide monotherapy (30 patients) and in combination with peginterferon alfa (6 patients); 11 of these patients were followed for more than 48 weeks, up to 54–118 weeks (5 and 6 patients, respectively). Results. After 48 weeks of treatment, there was a decrease in the median HDV RNA level from 7.1 log10 to 4.6 log10, with a median reduction of 2.2 log10 ( p &lt; 0.001) (2.1 log10 with monotherapy (p &lt; 0.001), 4.1 log10 with combination therapy), a virologic response rate of 64% (53% and 100%, respectively); and an aviremia rate of 18% (2 patients in each group). The median ALT level decreased from 63.0 to 33.0 U/L, the frequency of detection of normal ALT level increased from 24 to 67% (in the monotherapy group – from 18 to 69%). When treatment was continued for more than 48 weeks (up to 54–118 weeks), maintenance and/or improvement of virologic and biochemical response was observed in the majority of patients. The treatment was characterized by good tolerability, absence of serious adverse events, cases of treatment withdrawal, worsening of liver function indices in cirrhosis. Conclusion. Analysis of interim results of bulevirtide application in real practice demonstrated efficacy, safety and good tolerability of treatment, both in combination therapy and monotherapy, including in compensated liver cirrhosis. Further accumulation of treatment experience is necessary in order to develop an optimal treatment algorithm. Key words: bulevirtide, chronic hepatitis D, combined therapy, cirrhosis, monotherapy

Real-world non-interventional post-authorization safety study of long-term use of burosumab in children and adolescents with X-linked hypophosphatemia: first interim analysis.

X-linked hypophosphatemia (XLH) is a rare, progressive disorder characterized by excess fibroblast growth factor 23 (FGF23), causing renal phosphate-wasting and impaired active vitamin D synthesis. Burosumab is a recombinant human monoclonal antibody that inhibits FGF23, restoring patient serum phosphate levels. Safety data on long-term burosumab treatment are currently limited. This post-authorization safety study (PASS) aims to monitor long-term safety outcomes in children and adolescents (1-17 years) treated with burosumab for XLH. This first interim analysis reports the initial PASS safety outcomes. A 10-year retrospective and prospective cohort study. This PASS utilizes International XLH Registry (NCT03193476) data, which includes standard diagnostic and monitoring practice data at participating European centers. At data cut-off (13 May 2021), 647 participants were included in the International XLH Registry; 367 were receiving burosumab, of which 67 provided consent to be included in the PASS. Mean (SD) follow-up time was 2.2 (1.0) years. Mean (SD) age was 7.3 (4.3) years (range 1.0-17.5 years). Mean duration of burosumab exposure was 29.7 (25.0) months. Overall, 25/67 participants (37.3%) experienced ⩾1 adverse event (AE) during follow-up; 83 AEs were reported. There were no deaths, no AEs leading to treatment withdrawal, nor serious AEs related to treatment. The most frequently reported AEs were classified as 'musculoskeletal and connective tissue disorders', with 'pain in extremity' most frequently reported, followed by 'infections and infestations', with 'tooth abscess' the most frequently reported. In this first interim analysis of the PASS, covering the initial 2 years of data collection, the safety profile of burosumab is consistent with previously reported safety data. The PASS will provide long-term safety data over its 10-year duration for healthcare providers and participants with XLH that contribute to improvements in the knowledge of burosumab safety. European Union electronic Register of Post-Authorisation Studies: EUPAS32190.

A unique dermatologic adverse event from enfortumab vedotin

Enfortumab vedotin (EV) is a novel chemotherapeutic agent used in the treatment of metastatic urothelial cancer. Although rashes are reported as a common adverse event from this therapy, a paucity of literature is available on dermatologic toxicities to EV, especially with respect to bullous dermatoses. This case report will review a unique bullous dermatosis in the setting of EV therapy, including the diagnostic workup and management. Because cutaneous adverse events to chemotherapy and immunotherapy are common and can often result in dose reduction and treatment withdrawal for cancer patients, awareness of these manifestations and understanding how to manage them is crucial to providing quality care to this patient population.

Ethics and Medicolegal Aspects of Withdrawal of Treatment in Critical Care Patients without Advanced Directives in India: Who will Guard the Guardians Themselves?

Menon MR. Ethics and Medicolegal Aspects of Withdrawal of Treatment in Critical Care Patients without Advanced Directives in India: Who will Guard the Guardians Themselves? Indian J Crit Care Med 2024;28(1):15-17.