Cost-effectiveness of nivolumab and ipilimumab versus pembrolizumab and axitinib in advanced renal cell carcinoma with intermediate or poor prognostic risk: a Brazilian private healthcare system perspective.

Objective: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) have demonstrated significant clinical benefits as first-line (1 L) treatments for intermediate/poor-risk advanced renal cell carcinoma (aRCC) patients. This study aimed to assess the cost-effectiveness of NIVO + IPI versus PEM + AXI from a Brazilian private healthcare system perspective, utilizing a novel approach to estimate comparative efficacy between the treatments.

Methods: A three-state partitioned survival model (progression-free, progressed, and death) was developed to estimate costs, life-years (LYs), quality-adjusted LYs (QALYs), and the incremental cost-utility ratio (ICUR) over a 40-year time horizon.

Thoroughbred Racehorses in Hong Kong Require Vitamin D Supplementation to Mitigate the Risk of Low Vitamin D Status.

There is a paucity of data relating to the vitamin D status of racehorses. We hypothesised that the management of racehorses in Hong Kong (HK) predisposes to low vitamin D status unless they receive dietary supplementation. Serum concentrations of 25-hydroxyvitamin D (25OHD), 25-hydroxyvitamin D (25OHD) and total 25-hydroxyvitamin D (total 25OHD) for 79 non-grazing HK racehorses were compared with those for 22 racehorses training in the United Kingdom (UK) that grazed for ≥1 h/d, and for which published data exists.

Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma.

Network meta-analyses (NMAs) increasingly feature time-varying hazards to account for non-proportional hazards between different drug classes. This paper outlines an algorithm for selecting clinically plausible fractional polynomial NMA models. The NMA of four immune checkpoint inhibitors (ICIs) + tyrosine kinase inhibitors (TKIs) and one TKI therapy for renal cell carcinoma (RCC) served as case study.

Economic Evaluation of Nivolumab Versus Docetaxel for the Treatment of Advanced Squamous and Non-squamous Non-small Cell Lung Cancer After Prior Chemotherapy in China.

Objective: To evaluate the economic value of nivolumab versus docetaxel for advanced non-small cell lung cancer (aNSCLC) treatment after platinum-based chemotherapy in adults without epidermal growth factor receptor/anaplastic lymphoma kinase aberrations in China.

Methods: Partitioned survival models evaluated lifetime costs and benefits of nivolumab versus docetaxel by squamous and non-squamous histologies from a Chinese healthcare payer perspective. Progression-free disease, progressed disease, and death health states were considered over a 20-year time horizon.

A Matching-adjusted Indirect Comparison of Nivolumab Plus Cabozantinib Versus Pembrolizumab Plus Axitinib in Patients with Advanced Renal Cell Carcinoma.

Background: The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials.

Objective: To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib.

Design, Setting, And Participants: Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used.

Cost-Effectiveness of Nivolumab Plus Ipilimumab for the First-Line Treatment of Intermediate/Poor-Risk Advanced and/or Metastatic Renal Cell Carcinoma in Switzerland.

Objective: This study assessed the cost-effectiveness of nivolumab plus ipilimumab versus both sunitinib and pazopanib for the treatment of first-line unresectable advanced renal cell carcinoma (aRCC) from a healthcare system perspective in Switzerland.

Methods: A three-state partitioned survival model, consisting of progression-free, progressed disease, and death, was constructed. Efficacy estimates were based on data from the CheckMate 214 trial (NCT02231749) with a minimum follow-up of 42 months.

Static and Dynamic Stabilization of the Shoulder After Total Scapulectomy in an Electric Burn Patient.

An otherwise healthy 49-year-old man experienced a high-voltage electrical injury to the left shoulder resulting in total scapulectomy, partial calviculectomy, and a substantial soft tissue defect. The majority of the muscles around his shoulder were debrided because of necrosis, with only the pectoralis and latissimus dorsi muscles remaining attached to the humerus. Surprisingly, the patient's brachial plexus remained intact, and his left elbow, wrist, and hand function were preserved.

A Comparison of Alternative Network Meta-Analysis Methods in the Presence of Nonproportional Hazards: A Case Study in First-Line Advanced or Metastatic Renal Cell Carcinoma.

Objectives: Network meta-analysis (NMA) of time-to-event outcomes based on constant hazard ratios can result in biased findings when the proportional hazards (PHs) assumption does not hold in a subset of trials. We aimed to summarize the published non-PH NMA methods for time-to-event outcomes, demonstrate their application, and compare their results.

Methods: The following non-PH NMA methods were compared through an illustrative case study in oncology of 4 randomized controlled trials in terms of progression-free survival and overall survival: (1) 1-step or (2) 2-step multivariate NMAs based on traditional survival distributions or fractional polynomials, (3) NMAs with restricted cubic splines for baseline hazard, and (4) restricted mean survival NMA.

The Use of Biologic Wound Agents in Pediatric Reconstructions.

The indications for using biologic wound agents have expanded greatly since first being employed for acute burn management. The majority of the literature details the use of said agents in the adult population; however, there is little representation regarding their uses for reconstructing defects typically observed in the pediatric population. Ironically, children, and to a lesser extent adolescents, greatly benefit from their use given the reduced skin laxity and amount of surrounding tissue available for locoregional tissue transfer when compared with adults.

Budget impact of including ribociclib in combination with letrozole on US payer formulary: first-line treatment of post-menopausal women with HR+/HER2- advanced or metastatic breast cancer.

Objectives: The combination of a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor with the aromatase inhibitor letrozole is a safe and effective alternative to letrozole monotherapy for first-line hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This study evaluates the budget impact of using the CDK 4/6 inhibitor ribociclib plus letrozole as a first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer, from a United States (US) payer perspective.

Methods: A cohort-based budget impact model was used to calculate the incremental cost of introducing ribociclib plus letrozole over three years for the target population.

Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective.

Background: U.S. regulatory approvals of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors ribociclib and palbociclib as add-ons to letrozole greatly enhance the prospects for treating postmenopausal women with hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer.

A Comparison of the Full and Short-Scar Face-Lift Incision Techniques in Multiple Sets of Identical Twins.

Background: Choosing the ideal face-lift technique for a patient presents an added challenge for the plastic surgeon. With the multitude of well-established variations of this procedure, it would be beneficial to define which facioplasty technique produces the optimal result. By comparing the postoperative results from two of the most popularized face-lift incision techniques in monozygotic twins, it is hypothesized that the "best" technique may be determined.

Juvenile delinquency treatment and prevention: a literature review.

In the last three decades there has been ample research to demonstrate that instituting Multisystemic Therapy for serious juvenile offenders, keeping them in the community with intensive intervention, can significantly reduce recidivism. When there is recidivism, it is less severe than in released incarcerated juveniles. Multisystemic Therapy provides 24 h available parental guidance, family therapy, individual therapy, group therapy, educational support and quite importantly a change of peer group.

Functionalized poly(γ-Glutamic Acid) fibrous scaffolds for tissue engineering.

Poly(γ-glutamic acid) (γ-PGA) is a biocompatible, enzymatically-degradable, natural polymer with a higher resistance to hydrolysis than polyesters commonly used for tissue engineering scaffolds such as poly(L-lactide) (PLLA). Notably, γ-PGA's free carboxyl side groups allow for simple chemical functionalization, making it a versatile candidate for producing scaffolds. Here, a series of water-resistant fibrous scaffolds were engineered from ethyl (Et), propyl (Pr) and benzyl (Bn) esterifications of γ-PGA.

PINK1-dependent recruitment of Parkin to mitochondria in mitophagy.

Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease. Upon a loss of mitochondrial membrane potential (DeltaPsi(m)) in human cells, cytosolic Parkin has been reported to be recruited to mitochondria, which is followed by a stimulation of mitochondrial autophagy. Here, we show that the relocation of Parkin to mitochondria induced by a collapse of DeltaPsi(m) relies on PINK1 expression and that overexpression of WT but not of mutated PINK1 causes Parkin translocation to mitochondria, even in cells with normal DeltaPsi(m).

The kinase domain of mitochondrial PINK1 faces the cytoplasm.

Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of autosomal recessive familial Parkinson's disease (PD). Efforts in deducing the PINK1 signaling pathway have been hindered by controversy around its subcellular and submitochondrial localization and the authenticity of its reported substrates. We show here that this mitochondrial protein exhibits a topology in which the kinase domain faces the cytoplasm and the N-terminal tail is inside the mitochondria.

Treatment of hypovitaminosis D in infants and toddlers.

Context: Hypovitaminosis D appears to be on the rise in young children, with implications for skeletal and overall health.

Objective: The objective of the study was to compare the safety and efficacy of vitamin D2 daily, vitamin D2 weekly, and vitamin D3 daily, combined with supplemental calcium, in raising serum 25-hydroxyvitamin D [25(OH)D] and lowering PTH concentrations.

Design: This was a 6-wk randomized controlled trial.

Self-pay markets in health care: consumer Nirvana or caveat emptor?

As consumers face more incentives to make cost-conscious medical care decisions, some policymakers cite self-pay markets as models for consumer shopping. An analysis of the LASIK market revealed limited shopping overall, despite the fact that patients pay the full cost. For other self-pay procedures, consumers shop even less, for reasons ranging from urgency, to costs of obtaining price quotes, to quality concerns that prompt many consumers to rely on word-of-mouth recommendations.

Hospital-physicians relations: cooperation, competition, or separation?

Because many services performed in hospitals can safely and conveniently be performed in ambulatory settings, physicians have become owners of entities directly competing with hospitals for patients in a new medical arms race. Hospitals and medical staff physicians face growing tensions as a result of physicians' growing reluctance to take emergency department call and the consequences of hospitalists replacing physicians in the care of inpatients. Although there are increasing expectations that health system challenges will lead hospitals and physicians to collaborate, in many markets the willingness and ability for hospitals and physicians to work together is actually eroding.

Medicaid patients increasingly concentrated among physicians.

Despite increases in Medicaid payment rates and enrollment, the proportion of U.S. physicians accepting Medicaid patients has decreased slightly over the past decade, according to a national study by the Center for Studying Health System Change (HSC).

Hospitals' responses to nurse staffing shortages.

Hospitals have used a mix of short-term and long-term strategies to deal with nurse shortages, particularly efforts emphasizing nurse education, competitive compensation, and temporary staff. Interviews with health care leaders from Round Five of the Community Tracking Study indicate that these activities, in conjunction with other factors, have assisted in reducing shortages of hospital nurses. However, hospitals' actions have increased costs and raised concerns about their potential impact on patient care.

The transition from excess capacity to strained capacity in U.S. hospitals.

After many years of concern about excess hospital capacity, a growing perception exists that the capacity of some hospitals now seems constrained. This article explores the reasons behind this changing perception, looking at the longitudinal data and in-depth interviews for hospitals in four study sites monitored by the Community Tracking Study of the Center for Studying Health System Change. Notwithstanding the differences for individual hospitals, we observed that adjustments to the supply of hospital services tend to be slow and out of sync with changes in the demand for hospital services.

Construction activity in U.S. hospitals.

Hospital construction activity is increasing, but little information exists on what types of hospital capacity are affected and what is motivating specific efforts. Our analysis of Round Five Community Tracking Study data revealed four general types of activity: new hospital construction or expansion of existing general hospital capacity; new or expanded capacity in specialty services; replacement of aged facilities; and expansion of capacity-constrained services. Some of these actions are responsive to community need, but others resemble a medical-arms-race response.

A growing hole in the safety net: physician charity care declines again.

Continuing a decade-long trend, the proportion of U.S. physicians providing charity care dropped to 68 percent in 2004-05 from 76 percent in 1996-97, according to a national study from the Center for Studying Health System Change (HSC).

Can money buy quality? Physician response to pay for performance.

While pay for performance (P4P) has created a nationwide buzz among health plans, physicians and hospitals, most P4P initiatives are still on the drawing board, according to findings from the Center for Studying Health System Change's (HSC) 2005 site visits to 12 nationally representative communities. HSC focused on performance-based payment for physicians, finding that only two HSC communities-Orange County, Calif., and Boston-have significant physician P4P programs.