Cost-effectiveness of cenobamate for focal seizures in people with drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to estimate the cost-effectiveness of add-on cenobamate in the UK when used to treat drug-resistant focal seizures in adults who are not adequately controlled with at least two prior antiseizure medications, including at least one used adjunctively. METHODS: We estimated the cost per quality-adjusted life-year (QALY) for cenobamate compared to brivaracetam, eslicarbazepine, lacosamide, and perampanel in the UK National Health Service over a lifetime time horizon. We used a Markov cohort structure to determine response to treatment, using pooled data from three long-term studies of cenobamate. A network meta-analysis informed the likelihood of response to therapy with brivaracetam, eslicarbazepine, lacosamide, and perampanel relative to cenobamate. Once individuals discontinued treatment, they transitioned to subsequent treatment health states, including other antiseizure medicines, surgery, and vagus nerve stimulation. Costs included treatment, administration, routine monitoring, event management, and adverse events. Published evidence and expert opinion informed the likelihood of response to subsequent treatments, associated adverse events, and costs. Utility data were based on Short-Form six-dimension form utility. Discounting was applied at 3.5% per annum as per National Institute for Health and Care Excellence guidance. Uncertainty was explored through deterministic and probabilistic sensitivity analyses. RESULTS: In the base case, cenobamate led to cost savings of £51 967 (compared to brivaracetam), £21 080 (compared to eslicarbazepine), £33 619 (compared to lacosamide), and £28 296 (compared to perampanel) and increased QALYs of 1.047 (compared to brivaracetam), 0.598 (compared to eslicarbazepine), 0.776 (compared to lacosamide), and 0.703 (compared to perampanel) per individual over a lifetime time horizon. Cenobamate also dominated the four drugs across most sensitivity analyses. Differences were due to reduced seizure frequency with cenobamate relative to comparators. SIGNIFICANCE: Cenobamate improved QALYs and was less costly than brivaracetam, eslicarbazepine, lacosamide, and perampanel. Therefore, cenobamate may be considered as a cost-effective adjunctive antiseizure medication for people with drug-resistant focal seizures.

The formaldehyde treated guar meal and prill fat, agro industrial by-products as dietary rumen protected protein and energy source: improves growth performance, feed conversion, nutrient utilization, microbial protein synthesis, blood metabolites and economic efficiency in growing dairy buffalo (Bubalus bubalis) calves.

The study investigated the effects of protein replacement with formaldehyde-treated guar meal (FTGM) and prill fat (PF) in the diet on performance of growing dairy buffalo calves. Thirty-two feedlots Surti breed dairy buffalo calves (age, 7.31 ± 0.34 months and body weight, 90.69 ± 6.19 kg) were assigned into four dietary treatments (n-8 calves/each): (1) control group, supplied basal diet as per ICAR (2013) nutrient requirements; (2) FTGM group, 30% crude protein (CP) requirement of concentrate mixture (dry matter basis (DMB)) replaced with FTGM in basal diet; (3) PF group, supplied basal diet + 100 g PF; and (4) FTGM + PF group, 30% CP requirement of concentrate mixture (DMB) replaced with FTGM in the basal diet + 100 g PF for 280 days. All the treatment diets were isonitrogenous. Growth performance was improved in FTGM + PF and FTGM groups. Apparent digestibility (%) of CP was increased in FTGM and FTGM + PF diet, while digestibility (%) of ether extract (EE) was increased in PF group. Serum total protein, albumen, urea nitrogen, and creatinine concentrations were higher in FTGM + PF and FTGM groups, whereas total cholesterol and triglycerides levels were greater in FTGM + PF and PF groups. Calculated methane emission had a discernible influence of treatment in FTGM and FTGM + PF. The overall cost of feeding per kilogram gain was lowest in FTGM and FTGM + PF groups. In conclusion, 30% CP replacement with FTGM with or without PF improved the growth performance, feed conversion ratio, and nutrient utilization; supported efficient utilization of resources; and economized the rearing of growing dairy buffalo calves.

Integrated Behavioral Health: Definitions and Contexts.

Most children and adolescents with behavioral and mental health concerns first present to their pediatricians. Although pediatricians are fully cognizant of the importance of addressing behavioral and mental health concerns, they often find it difficult to deliver such care effectively and efficiently within a typical practice setting. Integration of medical and behavioral health care has emerged as a model to deliver such care. In the pediatric primary care practice, integrated behavioral health has been shown to be a cost-effective way to deliver high-quality care. This article describes basic definitions and contexts of integrated pediatric behavioral health.

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre's experience.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT. DESIGN: Retrospective cohort study. PATIENTS: PHPT assessed between 2006 - 2014 (n = 611) in a university hospital. MEASUREMENTS: Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes. RESULTS: Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralization was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035). CONCLUSIONS: Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

Correction to: Behaviour and risk assessment of fluopyram and its metabolite in cucumber (Cucumis sativus) fruit and in soil.

Unfortunately, the original publication of this paper contains a mistake. The correct name of the 3rd Author is Sunny H. Patel. The original article has been corrected.

Behaviour and risk assessment of fluopyram and its metabolite in cucumber (Cucumis sativus) fruit and in soil.

A field experiment was conducted to estimate residue persistence of fluopyram and its metabolite benzamide in cucumber fruits and soil and their risk assessment in humans and soil environment. Fluopyram (Kafka, 400 SC) was applied as soil drench twice at the interval of 15 days at the rate of 250 (standard dose) and 500 (double dose) g a.i. ha-1 (active ingredient per hectare). Cucumber fruits were collected at 0 (1 h), 1, 3, 5, 7, 10, 15, 20, 30, 40 and 50 days after second application. Soil samples were collected on 15th day after second application. Drench application resulted in detection of residues on the third day in standard dose at the levels of 0.056 mg kg-1 in cucumber fruit. The residue level increased until 20 days reaching 0.092 mg kg-1 followed by decrease to 0.068 mg kg-1 on 30th day after application. In double dose, the residues started accumulating from 0 day with initial levels of 0.093 mg kg-1 and persisted until 30th day. The levels varied between 0.123 and 0.184 mg kg-1 until 15th day of application followed by decrease to 0.127 mg kg-1 by 30th day. The residues reached below determination level (< 0.05 mg kg-1) on 40th day in both the doses after second application. The residue of metabolite benzamide was below determination level (< 0.05 mg kg-1) at both the doses. Hazard quotient (HQ) for residues levels at 15th and 30th day was less than one (HQ < 1). Hence, a pre-harvest interval of 15 days is suggested. Present data can be used to establish maximum residue limit (MRL) in India. The residue of fluopyram in soil on 15th day and the data on soil adsorption coefficient of fluopyram from literature suggests moderate mobility of fluopyram in soil. However, residues of metabolite of benzamide were not detected in soil. Further studies on translocation of fluopyram in soil over the time can be conducted for better understanding of environmental risk. To our knowledge, this is the first report on residue levels of fluopyram in any crop when applied as soil drench.

Assessment of Haemodynamic Response to Nonselective Beta-Blockers in Portal Hypertension by Phase-Contrast Magnetic Resonance Angiography.

A significant unmet need exists for accurate, reproducible, noninvasive diagnostic tools to assess and monitor portal hypertension (PHT). We report the first use of quantitative MRI markers for the haemodynamic assessment of nonselective beta-blockers (NSBB) in PHT. In a randomized parallel feasibility study in 22 adult patients with PHT and a clinical indication for NSBB, we acquired haemodynamic data at baseline and after 4 weeks of NSBB (propranolol or carvedilol) using phase-contrast MR angiography (PC-MRA) in selected intra-abdominal vessels. T1 mapping of liver and spleen was undertaken to assess changes in tissue composition. Target NSBB dose was achieved in 82%. There was a substantial reduction from baseline in mean average flow in the superior abdominal aorta after 4 weeks of NSBB therapy (4.49 ± 0.98 versus 3.82 ± 0.86 L/min, P = 0.03) but there were no statistically significant differences in flow in any other vessels, even in patients with >25% decrease in heart rate (47% of patients). Mean percentage change in liver and spleen T1 following NSBB was small and highly variable. In conclusion, PC-MRA was able to detect reduction in cardiac output by NSBB but did not detect significant changes in visceral blood flow or T1. This trial was registered with the ISRCTN registry (ISRCTN98001632).

The Cost-effectiveness of Pixantrone for Third/Fourth-line Treatment of Aggressive Non-Hodgkin's Lymphoma.

PURPOSE: Aggressive non-Hodgkin's lymphoma (aNHL) is associated with poor long-term survival after relapse, and treatment is limited by a lack of consensus regarding standard of care. Pixantrone was studied in a randomized trial in patients with relapsed or refractory aNHL who had failed ≥ 2 lines of therapy, demonstrating a significant improvement in complete or unconfirmed complete response and progression-free survival (PFS) compared with investigators' choice of single-agent therapy. The objective of this study was to assess the health economic implications of pixantrone versus current clinical practice (CCP) in the United Kingdom for patients with multiply relapsed or refractory aNHL receiving their third or fourth line of treatment. METHODS: A semi-Markov partition model based on overall survival and PFS was developed to evaluate the lifetime clinical and economic impact of treatment of multiply relapsed or refractory aNHL with pixantrone versus CCP. The empirical overall survival and PFS data from the PIX301 trial were extrapolated to a lifetime horizon. Resource use was elicited from clinical experts, and unit costs and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom's National Health Service and personal social services. Outcomes evaluated were total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty around the results. FINDINGS: Pixantrone was estimated to increase life expectancy by a mean of 10.8 months per patient compared with CCP and a mean gain of 0.56 discounted QALYs. The increased health gains were associated with an increase in discounted costs of approximately £18,494 per patient. The incremental cost-effectiveness ratio of pixantrone versus CCP was £33,272 per QALY gained. Sensitivity and scenario analyses suggest that the incremental cost-effectiveness ratio was sensitive to uncertainty in the PFS and overall survival estimates and the utility values associated with each health state. IMPLICATIONS: Pixantrone may be considered both clinically effective and cost-effective for patients with multiply relapsed or refractory aNHL who currently have a high level of unmet need.

Health insurance, patient protection and Affordable Care Act, and young adults.

In summary, the ACA aims to correct some of the shortcomings of our current health insurance systems. It aims to make health insurance more affordable and more accessible and the health insurance systems easier to navigate. For the young adult population, it aims to protect more individuals by allowing them to stay on their parent's insurance longer and by making it easier to choose an insurance plan that is right for them. Those with preexisting medical conditions do not have to worry about being excluded from a health plan because of their medical history. The law is also making health insurance mandatory, which may help prevent young adults who fall ill from incurring large medical bills. Initial outcomes from the implementation of the ACA have shown both positive and negative responses. All in all, it is giving young adults more options when it comes to obtaining health insurance. As part of discussion with adolescents and young adults, physicians may take into consideration key points summarized in Table 4.

Medical home and transition planning for children and youth with special health care needs.

Although many physicians may practice medical home medicine, most of the health care system is set up for acute episodic care. For children and youth with special health care needs (CYSHCN), this is costly and inefficient care and unsatisfactory for the patient and family. Transition or the purposeful planned movement of adolescents and young adults with chronic conditions from child-centered to adult-centered care began to evolve in the 1980s as more and more CYSHCN survived into adulthood. There is some progress being made in the implementation of the medical home that may facilitate a more effective transition of young individuals who have developmental disabilities. The greatest barrier to successful transition remains ensuring affordable, continuous health insurance coverage for all young people with special health care needs throughout adolescence and adulthood and engaging adult-oriented health care systems to take over the medical care of these young individuals.

Community group practices in Canada: are they ready to reform their practice?

INTRODUCTION: Governments and healthcare organizations in Canada are reforming the clinical practice structures and policies to deliver primary care to the population. A key component of primary healthcare reform is the establishment of an interdisciplinary, community-based team approach to patient care. This study was undertaken to provide in-depth insight regarding primary healthcare providers' beliefs and attitudes in regard to their current group practice, what changes they believe are occurring and those necessary to reform group practice settings, their willingness to embrace changes, and the challenges they face to realize the proposed reform. METHODS: This study employed a mixed-method research design (qualitative and quantitative data collection techniques) through day-long focus groups of primary healthcare professionals (eg, family physicians, specialists, dieticians, psychologists) from across Canada. RESULTS: There is considerable variation in the composition of primary care group practices across Canada. Respondents report that group practices are little more than an economic convenience to facilitate sharing of resources. Even when a practice is composed of several disciplines, there is little to no organized or systematic interaction among healthcare professionals aimed at improving patient care, lack of clarity as to identified leaders/managers of the team, and inconsistencies in the model of care provided to patients. However, there is a perception of value and benefit in working in a cohesive group practice to improve patient care. DISCUSSION: Findings revealed that although healthcare providers report themselves ready to make the necessary changes and willing to move to interdisciplinary team-based practices, there are substantive challenges that impede a movement to truly effective interdisciplinary team practice and functioning. These challenges include the type and allocation of funding, interprofessional healthcare provider education, changing the healthcare provision model, and barriers among healthcare professionals regarding shared and equitable team accountability for patient health outcomes.

Value of sports pre-participation examination in health care for adolescents.

Though adolescence is typically perceived as a time of good health in many places in the world,the reality is that adolescents have many health problems, including medical and behavioral disorders. The ideal location for health maintenance visits is the office of a clinician who has an established relationship with the adolescent patient. The clinician can use the interest of youth for sports to improve the health care of these youth in various ways, as reviewed in this article. A sports pre-participation examination (PPE) is recommended before the adolescent engages in organized sports. During this evaluation, various issues can be covered, including anticipatory guidance for sports participation, stress involved with organized sports, drug or supplement abuse in sports, eating disorders, and weight control practices, in-jury prevention, principles of sports participation, the importance of regular physical activity and normal growth and development. The pre-participation examination is reviewed in this article, including taking a proper history, performing the physical examination, and ordering appropriate laboratory tests. Youth with medical illnesses can be clinician-directed to the sports activities that are best and safest for them. Keeping youth active in some type of physical activity is important and thus, the examination can be used to allow full or partial participation in all or only some sports. This paper summarizes the clinician's approach to using sports activities as a way of improving the health of youth.