Murad, M. Hassan

Introduction Hypercalcaemia of malignancy (HCM) is the second most common cause of hypercalcaemia and is associated with significant morbidity and mortality. Several treatment options are available including pharmacological therapy with bisphosphonates, denosumab, glucocorticoids and calcimimetics, as well as conventional therapy with hydration and possibly calcitonin. While guidelines have previously considered treatment effects, no guideline has yet considered a range of contextual factors impacting recommendations for the management. The aim of this study was to summarise the available evidence on important decisional factors for the development of guidelines for the treatment of HCM. These include patient’s values and preferences, cost, acceptability, feasibility and equity. Methods and analysis This protocol is registered in PROSPERO (registration number: CRD42021264371). This is a systematic review of observational studies, case series, trials, reviews and qualitative studies involving treatment of adult patients with HCM. We will develop and execute two independent search strategies using five databases: PubMed, Medline (OVID), Embase.com, CINAHL (EBSCO) and Cochrane, and review their combined output. Two reviewers will screen titles and abstracts and full texts and will implement data abstraction from relevant studies independently and in duplicate. The outcomes of interest are the decisional factors that influence drug selection, with possible subgroup summaries by drug class or aetiology of HCM. We will present the data collected in a narrative and thematic approach. Ethics and dissemination Ethical approval is not applicable for our study, since we will only collect data from available literature. This systematic review will be submitted to a peer-reviewed journal when completed.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC). OBJECTIVE: To compare the efficacy and safety of the two most commonly used cisplatin-based regimens; gemcitabine, and cisplatin (GC) vs. accelerated (dose-dense: dd) or conventional methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). METHODS: We searched MEDLINE, Embase, Scopus and other sources. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. RESULTS: We identified 24 studies. Efficacy outcomes were comparable between MVAC and GC for MIBC. dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95%CI 1.15–1.82) and all-cause mortality at longest follow-up (OR 0.63; 95%CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95%CI 0.13–0.80), anemia (OR 0.32; 95%CI 0.18–0.54), nausea and vomiting (OR 0.27; 95%CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95%CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95%CI 0.01–0.31). Certainty in the estimates was very low for most outcomes. CONCLUSIONS: Efficacy and safety outcomes were comparable between MVAC and GC for MIBC. Including non-peer-reviewed studies showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice.

Abstract Background: Sickle cell disease (SCD) is a life-limiting inherited hemoglobinopathy that results in significant complications and affects quality of life. Hematopoietic stem cell transplantation (HSCT) is currently the only curative intervention for SCD; however, guidelines are needed to inform how to apply HSCT in clinical practice. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and health professionals in their decisions about HSCT for SCD. Methods: The multidisciplinary guideline panel formed by ASH included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews (through 2019). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 8 recommendations to help patients and providers assess how individuals with SCD should consider the timing and type of HSCT. Conclusions: The evidence review yielded no randomized controlled clinical trials for HSCT in SCD; therefore, all recommendations are based on very low certainty in the evidence. Key recommendations include considering HSCT for those with neurologic injury or recurrent acute chest syndrome at an early age and to improve nonmyeloablative regimens. Future research should include the development of a robust SCD registry to serve as a comparator for HSCT studies.

Abstract Cycle threshold (CT) values are correlated with the amount of viral nucleic acid in a sample and may be obtained from some qualitative real-time polymerase chain reaction tests used for diagnosis of most patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, CT values cannot be directly compared across assays, and they must be interpreted with caution as they are influenced by sample type, timing of sample collection, and assay design. Presently, the correlation between CT values and clinical outcomes is not well understood. We conducted a systematic review and meta-analysis of published studies through April 19, 2021, that reported an association between CT values and hospitalization, disease severity, and mortality in patients ≥18 years old with SARS-CoV-2. A meta-analysis of 7 studies showed no significant difference in mean CT values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with CT values <25 had a high risk of more severe disease and mortality than patients with CT values >30 (odds ratio [OR], 2.31; 95% CI, 1.70 to 3.13; and OR, 2.95; 95% CI, 2.19 to 3.96; respectively). The odds of increased disease severity and mortality were less pronounced in patients with CT values of 25–30 compared with >30.

SummaryBackgroundNonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. There is a major need to understand the efficacy of different pharmacological agents for the treatment of NASH.AimTo assess the relative rank‐order of different pharmacological interventions in fibrosis improvement and NASH resolution.MethodsA comprehensive search of several databases was conducted by an experienced librarian. We included randomised controlled‐trials (RCTs) comparing pharmacological interventions in patients with biopsy‐proven NASH. The primary outcome was ≥1 stage improvement in fibrosis. The secondary outcome was NASH resolution.ResultsA total of 26 RCTs with 23 interventions met the eligibility criteria. Lanifibranor and obeticholic acid had the highest probability of being ranked the most effective intervention for achieving ≥1 stage of fibrosis improvement (SUCRA 0.78) and (SUCRA 0.77), respectively. For NASH resolution, semaglutide, liraglutide and vitamin E plus pioglitazone had the highest probability of being ranked the most effective intervention for achieving NASH resolution (SUCRA 0.89), (SUCRA 0.84) and (SUCRA 0.83), respectively. Lanifibranor, obeticholic acid, pioglitazone and vitamin E were significantly better than placebo in achieving ≥1 stage of fibrosis improvement. Conversely, semaglutide, liraglutide, vitamine E plus pioglitazone, pioglitazone, lanifibranor and obeticholic acid were significantly better than placebo in achieving NASH resolution.ConclusionThese data provide relative rank‐order efficacy of various NASH therapies in terms of their improvements in liver fibrosis and NASH resolution. Therapies that have been shown to improve NASH resolution may be combined with therapies that have an antifibrotic effect to further boost treatment response rate in future.

The high prevalence of uncontrolled hypertension in underserved populations is a major cause of health disparities in the United States and requires innovative health care delivery interventions. We conducted a systematic review of randomized controlled trials and comparative observational studies examining the effectiveness of contemporary systems change and quality improvement interventions aimed at improving blood pressure (BP) control published from 2010 to 2020. We included studies evaluating multicomponent practice improvement interventions conducted in the United States in community health centers. We identified 26 studies including 48 187 patients with hypertension with a high proportion of racial/ethnic minorities, low socioeconomic status, and a high burden of chronic illness. Multicomponent interventions led to an average reduction of 5 to 10 mm Hg in systolic BP. Four studies demonstrated the effectiveness of integrating pharmacists into community health centers for BP management and reduced cardiovascular disparities for at-risk populations. Five studies demonstrated the effectiveness of integrating community health workers into care workflows leading to reduction in BP and high patient satisfaction. Five studies used the electronic medical record as a tool for population management and showed only modest reduction in BP. One study demonstrated the effectiveness of incentivizing clinics with higher payments for uninsured and Medicaid patients meeting performance criteria. Very few studies evaluated treatment complications or medications side effects. Multicomponent quality improvement interventions instituted in community health centers are effective in lowering BP. Several components of the interventions were identified as being associated with higher efficacy.

Abstract Background As the use of antibiotics during the peripartum period increases, the incidence of autoimmune disorders and autism spectrum disorders (ASDs) is also increasing. In this study, we aim to assess if antibiotic exposure during the peripartum period affects the incidence of autoimmune diseases and ASD in the offspring. Methods We identified children (< 18 years of age) born in Olmsted County from January 1, 2003 through December 31, 2012. Offspring with celiac disease (CD), inflammatory bowel disease (IBD), or ASD diagnoses were matched to two controls on birth date, index date, mother’s age at delivery, and sex. Data from the mother’s medical records were retrieved to determine peripartum antibiotics use. Results A total of 242 cases and 484 matched controls were included in this study. Median age at the last follow-up was 11.3 years (range: 0.5–14.9), 73% were males in both groups. Odds of CD diagnosis was not statistically different between vaginal delivery with antibiotics compared with vaginal delivery with no antibiotics (odds ratio [OR] = 0.76, 95% confidence interval [CI]: 0.32–1.85), similarly in IBD (OR = 2.41, 95% CI: 0.53–10.98) and ASD (OR = 1.00, 95% CI:0.55–1.79). Preeclampsia or eclampsia was associated with offspring CD (OR = 3.20, 95% CI: 1.05–9.78). Smoking history and diabetes mellitus were associated with offspring ASD (OR = 1.84, 95% CI: 1.22–2.77 and OR = 2.01, 95% CI: 1.03–3.91, respectively). Conclusion In this cohort, we found no statistically significant association between peripartum antibiotics exposure and the development of CD, IBD, or ASD.