Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 and BA.5 subvariant predominance: a systematic literature review.

PURPOSE: To evaluate clinical outcomes associated with sotrovimab use during Omicron BA.2 and BA.5 predominance. METHODS: Electronic databases were searched for observational studies published in peer-reviewed journals, preprint articles and conference abstracts from January 1, 2022 to February 27, 2023. RESULTS: The 14 studies identified were heterogeneous in terms of study design, population, endpoints and definitions. They included > 1.7 million high-risk patients with COVID-19, of whom approximately 41,000 received sotrovimab (range n = 20-5979 during BA.2 and n = 76-1383 during BA.5 predominance). Four studies compared the effectiveness of sotrovimab with untreated or no monoclonal antibody treatment controls, two compared sotrovimab with other treatments, and three single-arm studies compared outcomes during BA.2 and/or BA.5 versus BA.1. Five studies descriptively reported rates of clinical outcomes in patients treated with sotrovimab. Rates of COVID-19-related hospitalization or mortality (0.95-4.0% during BA.2; 0.5-2.0% during BA.5) and all-cause mortality (1.7-2.0% during BA.2; 3.4% during combined BA.2 and BA.5 periods) among sotrovimab-treated patients were consistently low. During BA.2, a lower risk of all-cause hospitalization or mortality was reported across studies with sotrovimab versus untreated cohorts. Compared with other treatments, sotrovimab was associated with a lower (molnupiravir) or similar (nirmatrelvir/ritonavir) risk of COVID-19-related hospitalization or mortality during BA.2 and BA.5. There was no significant difference in outcomes between the BA.1, BA.2 and BA.5 periods. CONCLUSIONS: This systematic literature review suggests continued effectiveness of sotrovimab in preventing severe clinical outcomes during BA.2 and BA.5 predominance, both against active/untreated comparators and compared with BA.1 predominance.

Economic burden of COVID-19 for employers and employees in the United States.

OBJECTIVE: Describe the economic burden of COVID-19 on employers and employees in the United States (US). METHODS: A targeted literature review was conducted to evaluate the impact of COVID-19 on US-based employers and employees in terms of healthcare resource utilization (HCRU), medical costs, and costs associated with work-loss. Searches were conducted in MEDLINE, Embase, and EconLit using a combination of disease terms, populations, and outcomes to identify articles published from January 2021 to November 4, 2022. As data from the employer perspective were lacking, additional literature related to influenza were included to contextualize the impact of COVID-19, as it shifts into an endemic state, within the existing respiratory illness landscape. RESULTS: A total of 41 articles were included in the literature review. Employer and employee perspectives were not well represented in the literature, and very few articles overlapped on any given outcome. HCRU, costs, and work impairment vary by community transmission levels, industry type, population demographics, telework ability, mitigation implementation measures, and company policies. Work-loss among COVID-19 cases were higher among the unvaccinated and in the week following diagnosis and for some, these continued for 6 months. HCRU is increased in those with COVID-19 and COVID-19-related HCRU can also continue for 6 months. CONCLUSIONS: COVID-19 continues to be a considerable burden to employers. The majority of COVID-19 cases impact working age adults. HCRU is mainly driven by outpatient visits, while direct costs are driven by hospitalization. Productivity loss is higher for unvaccinated individuals. An increased focus to support mitigation measures may minimize hospitalizations and work-loss. A data-driven approach to implementation of workplace policies, targeted communications, and access to timely and appropriate therapies for prevention and treatment may reduce health-related work-loss and associated cost burden.

In January 2020, the US government declared COVID-19 a public health emergency. This lasted until May 2023. To fight this health emergency, the US government provided free testing, vaccination, and treatment. Although the US government has declared the emergency over, COVID-19 continues to infect people. For people with private health insurance, costs associated with COVID-19 patient healthcare have now been transferred from the government to employers. In this study, we collected information from published scientific articles about the costs of COVID-19 for employers and workers in the US. We found that people who were not vaccinated against COVID-19 required more medical care and cost more than people who were vaccinated. In some cases, this trend lasted for as long as 6 months. This was mostly because of workers missing work, not working effectively while sick, and needing to be hospitalized. People who could work from home, whose companies had policies to prevent infections, and who took steps to avoid getting infected needed less medical care and missed work less often. This information may be used to help develop policies, communications, and guidance to prevent COVID-19 and limit its impact on employers and workers.

Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review.

PURPOSE: Emerging SARS-CoV-2 variants have impacted the in vitro activity of sotrovimab, with variable fold changes in neutralization potency for the Omicron BA.2 sublineage and onward. The correlation between reduced in vitro activity and clinical efficacy outcomes is unknown. A systematic literature review (SLR) evaluated the effectiveness of sotrovimab on severe clinical outcomes during Omicron BA.2 predominance. METHODS: Electronic databases were searched for peer-reviewed journals, preprint articles, and conference abstracts published from January 1-November 3, 2022. RESULTS: Five studies were included, which displayed heterogeneity in study design and population. Two UK studies had large samples of patients during BA.2 predominance: one demonstrated clinical effectiveness vs molnupiravir during BA.1 (adjusted hazard ratio [aHR] 0.54, 95% CI 0.33-0.88; p = 0.014) and BA.2 (aHR 0.44, 95% CI 0.27-0.71; p = 0.001); the other reported no difference in the clinical outcomes of sotrovimab-treated patients when directly comparing sequencing-confirmed BA.1 and BA.2 cases (HR 1.17, 95% CI 0.74-1.86). One US study showed a lower risk of 30-day all-cause hospitalization/mortality for sotrovimab compared with no treatment during the BA.2 surge in March (adjusted relative risk [aRR] 0.41, 95% CI 0.27-0.62) and April 2022 (aRR 0.54, 95% CI 0.08-3.54). Two studies from Italy and Qatar reported low progression rates but were either single-arm descriptive or not sufficiently powered to draw conclusions on the effectiveness of sotrovimab. CONCLUSION: This SLR showed that the effectiveness of sotrovimab was maintained against Omicron BA.2 in both ecological and sequencing-confirmed studies, by demonstrating low/comparable clinical outcomes between BA.1 and BA.2 periods or comparing against an active/untreated comparator.

Efficacy and safety of TNF inhibitors in the treatment of juvenile idiopathic arthritis: a systematic literature review.

OBJECTIVE: A systematic literature review was conducted to summarize efficacy and safety data from studies that evaluated tumor necrosis factor inhibitors in patients with juvenile idiopathic arthritis (JIA). METHODS: Relevant publications were identified via online searches (cutoff: March 16, 2021). After screening search results, outcome data were extracted if the treatment arm included ≥ 30 patients. Outcomes were described narratively, with efficacy assessed by JIA-American College of Rheumatology (ACR) response criteria and safety assessed by the incidence of serious adverse events (SAEs) per 100 patient-years (100PY). RESULTS: Among 87 relevant publications included in the qualitative synthesis, 19 publications described 13 clinical trials. Across the 13 trials, the percentages of patients who achieved JIA-ACR30/50/70/90 responses at Week 12 with adalimumab ranged 71-94%, 68-90%, 55-61%, and 39-42%, respectively; with etanercept (Week 12), 73-94%, 53-78%, 36-59%, and 28%; with golimumab (Week 16), 89%, 79%, 66%, and 36%; and with infliximab (Week 14), 64%, 50%, and 22% (JIA-ACR90 not reported). SAE incidence across all time points ranged 0-13.7 SAE/100PY for adalimumab, 0-20.0 SAE/100PY for etanercept, and 10.4-24.3 SAE/100PY for golimumab (1 study). SAE incidence could not be estimated from the 2 infliximab publications. CONCLUSION: Tumor necrosis factor inhibitors are effective and well tolerated in the treatment of JIA, but additional evidence from head-to-head studies and over longer periods of time, especially in the context of the transition from pediatric to adult care, would be useful.

Newborns' Bonding and Attachment, Their Rhythms and Needs, Supporting Parents Appropriately: Guidelines for Interventions During the Perinatal Period from the French National College Of Midwives.

A newborn's sleep-wake rhythms are very specific, neurologically determined, and different from the pattern of adults; they require an adaptable and predictable response by parents, which will promotes bonding and attachments, constructed at the early stages of development. It also will influence the quality of subsequent emotional relationships and adaptation to life events. This parental adaptability should receive multiprofessional support starting in the perinatal period, focused on the screening and management of psychological vulnerability.

Young Children and Screens: Guidelines for Intervention during the Perinatal Period from the French National College of Midwives.

Screens and digital media are increasingly present in family environments. This article reports the published data about children's screen use in France and elsewhere. We next synthesize the scientific literature on the relations between screen use and child development and then summarize current national and international guidelines about children's screen use before the age of 5 years. Based on these elements, we propose clinical practice guidelines for counseling women during the perinatal period. Précis: Current knowledge on children's screen use and its relationship to their development is summarized including guidelines and suggestions to help parents monitor screen use.

Long-term safety outcomes of prekallikrein (Fletcher factor) deficiency: A systematic literature review of case reports.

Background: Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. Objective: We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reported comorbidities in patients with hereditary prekallikrein deficiency. Methods: We searched several medical literature databases for publications that reported data from patients with hereditary prekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubation time). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. Results: Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) were included. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and one with systemic lupus erythematosus). Conclusion: This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

Longterm Drug Survival of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis.

OBJECTIVE: To evaluate longterm drug survival (proportion of patients still receiving treatment) and discontinuation of etanercept (ETN), infliximab (IFX), adalimumab (ADA), certolizumab pegol (CZP), and golimumab (GOL) using observational data from patients with rheumatoid arthritis (RA). METHODS: Following a systematic literature review, drug survival at 12 and 12-24 months of followup was estimated by summing proportions of patients continuing treatment and dividing by number of studies. Drug survival at ≥ 36 months of followup was estimated through Metaprop. RESULTS: There were 170 publications included. In the first-line setting, drug survival at 12 months with ETN, IFX, or ADA was 71%, 69%, and 70%, respectively, while at 12-24 months the corresponding rates were 63%, 57%, and 59%. In the second-line setting, drug survival at 12 months with ETN, IFX, or ADA was 61%, 69%, and 55%, respectively, while at 12-24 months the corresponding rates were 53%, 39%, and 43%. Drug survival at ≥ 36 months with ETN, IFX, or ADA in the first-line setting was 59% (95% CI 46-72%), 49% (95% CI 43-54%), and 51% (95% CI 41-60%), respectively, while in the second-line setting the corresponding rates were 56% (95% CI 52-61%), 48% (95% CI 40-55%), and 41% (95% CI 36-47%). Discontinuation of ETN, IFX, and ADA at 36 months of followup was 38-48%, 42-62%, and 38-59%, respectively. Data on CZP and GOL were scarce. CONCLUSION: After > 12 months of followup, more patients with RA receiving ETN remain on treatment compared with other tumor necrosis factor inhibitors.

Long-term safety outcomes of prekillikrein (Fletcher factor) deficiency: A systematic literature review of case reports.

BACKGROUND: Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. OBJECTIVE: We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reportedcomorbidities in patients with hereditary prekallikrein deficiency. METHODS: We searched several medical literature databases for publications that reported data from patients with hereditaryprekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubationtime). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. RESULTS: Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) wereincluded. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and onewith systemic lupus erythematosus). CONCLUSION: This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: a systematic literature review.

BACKGROUND: The recognition of distinct molecular subgroups within cholangiocarcinoma (CC), along with the increasing availability of targeted therapies, suggests that further characterization of the prevalence and prognosis of frequently occurring subgroups may assist with the development of more effective treatment approaches for the management of CC. A systematic review was performed to investigate the prevalence of isocitrate dehydrogenase 1 (IDH1) mutations (mIDH1) in patients with CC, the possible clinical and prognostic significance of mIDH1, and the presence of co-mutations in tumors with mIDH1. METHODS: This review was conducted using the Cochrane dual-reviewer methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol (PRISMA-P) guidelines. Searches were performed in Embase, MEDLINE, the Cochrane Central Trials Register and Database of Systematic Reviews, and other Cochrane Library assets using terms for CC and mIDH1 with no language or date restrictions for articles published up to December 31, 2017. Searches were also performed of abstracts presented at the following conferences in 2016 and 2017: American Society of Clinical Oncology (ASCO), ASCO-Gastrointestinal Cancers Symposium (ASCO-GI), the European Society for Medical Oncology (ESMO), and ESMO-Asia. Screening was performed separately by two reviewers and cross-checked. Any discrepancies between reviewers were resolved by a senior researcher. Data from all selected references were recorded in a data extraction grid. RESULTS: A total of 46 publications met the inclusion criteria and were included in the systematic review. Of these publications, 45 reported the frequency of mIDH1 among a total sample of 5,393 patients with CC. mIDH1 was enriched in intrahepatic CC (ICC), with 552 (13.1%; 95% CI, 12.1-14.2) of the 4,214 patients with ICC having the mutation compared with 9 (0.8%; 95% CI, 0.4-1.5%) of the 1,123 patients with extrahepatic CC (ECC). The percentage of females with mIDH1 CC (66.2%; 95% CI, 57.7-73.7%) was higher than in the overall CC population (44.4%). The frequency of mIDH1 in patients with ICC reported in individual studies ranged from 4.5-55.6%, and a significantly higher frequency was reported in non-Asian centers compared with Asian centers (weighted mean, 16.5% vs. 8.8%; P<0.001). The prevalence of mIDH1 in patients with ICC at USA centers was 18.0% (95% CI, 16.4-19.8%). Eleven publications reported the prevalence of co-mutations in patients with mIDH1 ICC, with the most frequent being AT-rich interactive domain-containing protein 1A (ARID1A) (22.0%), BRCA1-associated protein 1 (BAP1) (15.5%), and PBRM1 (13.3%). Eight publications investigated the possible prognostic significance of mIDH1. None of the studies reported a statistically significant association between mIDH1 and overall survival (OS), progression-free survival (PFS), or time to progression. CONCLUSIONS: This systematic review substantiates the prevalence of mIDH1 in CC and further characterizes clinical, pathologic, and genetic covariates within this sub-population. Co-mutation data may inform future studies of mechanisms of response and resistance to mIDH1-targeted therapies.

Efficacy and Safety of Combination Pharmacotherapy for Patients with Overactive Bladder: A Rapid Evidence Assessment.

CONTEXT: Oral pharmacotherapy consisting of antimuscarinics, ß3-adrenoreceptor agonists, or combinations of these agents forms the mainstay of overactive bladder (OAB) management. OBJECTIVE: To evaluate the efficacy and safety of combination therapy in patients with OAB. EVIDENCE ACQUISITION: A literature search was conducted in June 2018 using Embase, MEDLINE, and Cochrane databases via Ovid and relevant congress abstracts. Studies reporting the efficacy/safety of two antimuscarinics or a ß3-adrenoreceptor agonist plus an antimuscarinic were included. EVIDENCE SYNTHESIS: Publications reported on clinical efficacy, safety, and health-related quality of life (HRQoL) for mirabegron (M) plus solifenacin (S) from three 12-wk randomised controlled trials (RCTs)-SYMPHONY, SYNERGY, and BESIDE-and a 12-mo RCT, SYNERGY II. SYMPHONY reported statistically significant improvements in clinical symptoms and HRQoL with combination therapy versus solifenacin 5 mg (S5) and placebo. In SYNERGY, there were consistent improvements in urinary incontinence (UI) episodes/24 h and micturitions/24 h (coprimary endpoints), and in secondary efficacy parameters with mirabegron 25 mg (M25) + S5 and mirabegron 50 mg (M50) + S5 versus respective monotherapies. In patients with an inadequate response to S5 monotherapy (BESIDE), greater improvements in UI (primary endpoint) were noted for M50 + S5 versus S5 (p = 0.001). Combination therapy was noninferior to solifenacin 10 mg (S10) for reduction in UI and superior to S10 for improvement in micturition frequency (p < 0.001), and resulted in greater improvements from baseline in OAB-5 Dimension scores versus S5 and S10 (p < 0.01). In SYNERGY II, clinically meaningful and sustained improvements in clinical outcomes were observed for M50 + S5 versus M50 or S5. Combination therapy was well tolerated in all four trials. The incidence of adverse events (AEs) was similar across groups, and there were no notable differences in the incidence of specific AEs. Positive efficacy outcomes were observed in five studies of dual antimuscarinic therapy (trospium + solifenacin). CONCLUSIONS: Mirabegron plus solifenacin provides effective, well-tolerated treatment for patients with OAB. Limited data for dual antimuscarinic therapy suggest a benefit in patients with moderate-to-severe symptoms. PATIENT SUMMARY: Overactive bladder (OAB) is treated with medicines called antimuscarinics, such as solifenacin, propiverine, or trospium, or another ß-adrenoreceptor agonist medicine called mirabegron, which works in a different way. We looked at published scientific studies of patients with OAB treated with mirabegron plus solifenacin together, or with two antimuscarinics. We found that mirabegron plus solifenacin can help reduce symptoms and improve quality of life. Patients tolerate this treatment well, with few patients experiencing side effects.

A rapid evidence assessment of bleed-related healthcare resource utilization in publications reporting the use of direct oral anticoagulants for non-valvular atrial fibrillation.

Objective: Non-valvular atrial fibrillation (NVAF), a common cardiac arrhythmia, is associated with high morbidity and carries a substantial economic burden. Historically, vitamin K antagonists (VKAs; e.g. warfarin) have been used for therapy of NVAF, but recently several direct oral anticoagulants (DOACs) have been approved for prevention of stroke in patients with NVAF. This review summarizes the real-world evidence (RWE) for healthcare resource utilization (HRU) in patients receiving oral anticoagulants (VKAs and/or DOACs) for therapy of NVAF.Methods: A PRISMA-compliant literature search assessed Medline® and Embase® databases from 1 January 2011 to 4 May 2017, and the National Health Service Economic Evaluation Database from 1 January 2011 to 31 December 2015. Publications were included if they reported observational data from real-world use of one or more anticoagulant therapies. Outcomes of interest included hospitalizations, length of stay (LOS), mortality and costs.Results: Twenty-eight publications were included. Apixaban and dabigatran were associated with fewer bleed-related hospitalizations than warfarin. Bleed-related LOS were generally longer for warfarin than for DOACs. Bleed-related treatment costs were lower for patients receiving apixaban or receiving dabigatran than patients receiving rivaroxaban or receiving warfarin. Bleed-related mortality in patients receiving oral anticoagulation for treatment of NVAF were low across all DOACs and warfarin.Conclusions: The limited available evidence for HRU burden among patients receiving oral anticoagulation for NVAF suggests that DOACs (particularly apixaban and dabigatran) offer some degree of benefit in terms of HRU outcomes, compared with warfarin. Further work is required to understand HRU outcomes in patients receiving DOACs.

A quick scoping review of efficacy, safety, economic, and health-related quality-of-life outcomes of short- and long-acting erythropoiesis-stimulating agents in the treatment of chemotherapy-induced anemia and chronic kidney disease anemia.

Erythropoiesis-stimulating agents (ESAs) are man-made forms of erythropoietin used in the treatment of anemia. This quick-scoping review of systematic literature reviews (SLRs) was conducted to define the clinical, economic, and health-related quality of life (HRQoL) outcomes for short-acting and long-acting ESAs in patients with chronic kidney disease-induced anemia (CKD-IA) and patients with chemotherapy-induced anemia (CIA). Embase, Medline, and the Cochrane Database of Systematic Reviews were searched from their establishment until October 2017. SLRs related to the use of short-acting and long-acting ESAs in the treatment of CIA and CKD-IA were included. Forty-eight studies met the inclusion criteria. The evidence suggests little difference in efficacy, HRQoL, and safety outcomes among ESA types. Cost-effectiveness and market price are likely to become determining factors driving the choice of agent. Comparative studies and costing models accounting for the utilization of biosimilars are needed to establish which ESAs are more cost-effective.

Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial.

Importance: Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes. Objective: To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. Design, Settings, and Participants: The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. Interventions: Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations. Main Outcomes and Measures: The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval. Results: Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19). Conclusion and Relevance: This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01731431.

Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review.

OBJECTIVE: Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. METHODS: Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab. RESULTS: Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies. CONCLUSIONS: Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis.

Albuminuria, serum creatinine, and estimated glomerular filtration rate as predictors of cardio-renal outcomes in patients with type 2 diabetes mellitus and kidney disease: a systematic literature review.

BACKGROUND: Albuminuria, elevated serum creatinine and low estimated glomerular filtration rate (eGFR) are pivotal indicators of kidney decline. Yet, it is uncertain if these and emerging biomarkers such as uric acid represent independent predictors of kidney disease progression or subsequent outcomes among individuals with type 2 diabetes mellitus (T2DM). This study systematically examined the available literature documenting the role of albuminuria, serum creatinine, eGFR, and uric acid in predicting kidney disease progression and cardio-renal outcomes in persons with T2DM. METHODS: Embase, MEDLINE, and Cochrane Central Trials Register and Database of Systematic Reviews were searched for relevant studies from January 2000 through May 2016. PubMed was searched from 2013 until May 2016 to retrieve studies not yet indexed in the other databases. Observational cohort or non-randomized longitudinal studies relevant to albuminuria, serum creatinine, eGFR, uric acid and their association with kidney disease progression, non-fatal cardiovascular events, and all-cause mortality as outcomes in persons with T2DM, were eligible for inclusion. Two reviewers screened citations to ensure studies met inclusion criteria. RESULTS: From 2249 citations screened, 81 studies were retained, of which 39 were omitted during the extraction phase (cross-sectional [n = 16]; no outcome/measure of interest [n = 13]; not T2DM specific [n = 7]; review article [n = 1]; editorial [n = 1]; not in English language [n = 1]). Of the remaining 42 longitudinal study publications, biomarker measurements were diverse, with seven different measures for eGFR and five different measures for albuminuria documented. Kidney disease progression differed substantially across 31 publications, with GFR loss (n = 9 [29.0%]) and doubling of serum creatinine (n = 5 [16.1%]) the most frequently reported outcome measures. Numerous publications presented risk estimates for albuminuria (n = 18), serum creatinine/eGFR (n = 13), or both combined (n = 6), with only one study reporting for uric acid. Most often, these biomarkers were associated with a greater risk of experiencing clinical outcomes. CONCLUSIONS: Despite the utility of albuminuria, serum creatinine, and eGFR as predictors of kidney disease progression, further efforts to harmonize biomarker measurements are needed given the disparate methodologies observed in this review. Such efforts would help better establish the clinical significance of these and other biomarkers of renal function and cardio-renal outcomes in persons with T2DM.

The experiences of women with polycystic ovary syndrome on a very low-calorie diet.

Polycystic ovary syndrome (PCOS) is variously reported to affect between 5% and 26% of reproductive age women in the UK and accounts for up to 75% of women attending fertility clinics due to anovulation. The first-line treatment option for overweight/obese women with PCOS is diet and lifestyle interventions. However, optimal dietary guidelines are missing, with very little research having been done in this area. This paper presents the findings from a qualitative study (using semistructured interviews) of ten obese women who had PCOS and who had used LighterLife Total (LLT), a commercial weight loss program which utilizes a very low-calorie diet in conjunction with behavioral change therapy underpinned by group support. We investigated the women's history of obesity, their experiences of other diets compared with LLT, and the on-going impact that this has had on their lives. Findings show that most women reported greater success using this weight loss program in terms of achieving and maintaining weight loss when compared with other diets. Furthermore, all the women nominated LLT as their model weight loss intervention with only a few modifications.

Weight loss for women with and without polycystic ovary syndrome following a very low-calorie diet in a community-based setting with trained facilitators for 12 weeks.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects between 2% and 26% of reproductive-age women in the UK, and accounts for up to 75% of anovulatory infertility. The major symptoms include ovarian disruption, hyperandrogenism, insulin resistance, and polycystic ovaries. Interestingly, at least half of the women with PCOS are obese, with the excess weight playing a pathogenic role in the development and progress of the syndrome. The first-line treatment option for overweight/obese women with PCOS is diet and lifestyle interventions; however, optimal dietary guidelines are missing. Although many different dietary approaches have been investigated, data on the effectiveness of very low-calorie diets on PCOS are very limited. MATERIALS AND METHODS: The aim of this paper was to investigate how overweight/obese women with PCOS responded to LighterLife Total, a commercial very low-calorie diet, in conjunction with group behavioral change sessions when compared to women without PCOS (non-PCOS). RESULTS: PCOS (n=508) and non-PCOS (n=508) participants were matched for age (age ±1 unit) and body mass index (body mass index ±1 unit). A 12-week completers analysis showed that the total weight loss did not differ significantly between PCOS (n=137) and non-PCOS participants (n=137) (-18.5±6.6 kg vs -19.4±5.7 kg, P=0.190). Similarly, the percentage of weight loss achieved by both groups was not significantly different (PCOS 17.1%±5.6% vs non-PCOS 18.2%±4.4%, P=0.08). CONCLUSION: Overall, LighterLife Total could be an effective weight-loss strategy in overweight/obese women with PCOS. However, further investigations are needed to achieve a thorough way of understanding the physiology of weight loss in PCOS.

Morphological and health-related changes associated with a 12-week self-guided exercise programme in overweight adults: a pilot study.

Over 12 weeks, supervised physical activity (PA) interventions have demonstrated improvements in morphological and health parameters, whereas community walking programmes have not. The present study piloted a self-guided programme for promoting PA and reducing sedentary behaviour in overweight individuals and measured its effect on a range of health outcomes. Six male and 16 female sedentary adults aged 48.5 ± 5.5 years with body mass index (BMI) 33.4 ± 6.3 kg m(-2) were assessed for anthropometric variables, blood pressure, functional capacity, well-being and fatigue. After an exercise consultation, participants pursued their own activity and monitored PA points weekly. At baseline, mid-point and 12 weeks, eight participants wore activity monitors, and all participants undertook a 5-day food diary to monitor dietary intake. In 17 completers, mass, BMI, sit-to-stand, physical and general fatigue had improved by 6 weeks. By 12 weeks, waist, sagittal abdominal diameter (SAD), diastolic blood pressure, well-being and most fatigue dimensions had also improved. Throughout the intervention, PA was stable, energy intake and lying time decreased and standing time increased; thus, changes in both energy intake and expenditure explain the health-related outcomes. Observed changes in function, fatigue and quality of life are consistent with visceral fat loss and can occur at levels of weight loss which may not be considered clinically significant.

The effect of very low-calorie diets on renal and hepatic outcomes: a systematic review.

Very low-calorie diets (VLCDs) are an effective means by which to induce clinically significant weight loss. However, their acceptance by health care practitioners and the public is generally lower than that for other nonsurgical weight loss methods. Whilst there is currently little evidence to suggest they have any detrimental effect on hepatic and renal health, data assessing these factors remain limited. We carried out a systematic review of the literature on randomized controlled trials that had a VLCD component and that reported outcomes for hepatic and renal health, published between January 1980 and December 2012. Cochrane criteria were followed, and eight out of 196 potential articles met the inclusion criteria. A total of 548 participants were recruited across the eight studies. All eight studies reported significant weight loss following the VLCD. Changes in hepatic and renal outcomes were variable but generally led to either no change or improvements in either of these. Due to the heterogeneity in the quality and methodology of the studies included, the effect of VLCDs on hepatic and renal outcomes remains unclear at this stage. Further standardized research is therefore required to fully assess the impact of VLCDs on these outcome measures, to better guide clinical practice.