Abstract

International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review and meta-analysis to investigate the efficacy and safety of interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia. Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomized and quasi-randomized controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic nonhypovolaemic hypotonic hyponatraemia. Where appropriate, outcome data were synthesized in a meta-analysis. A total of 45 716 bibliographic records were identified from the searches and 18 trials (assessing conivaptan, lixivaptan, tolvaptan and satavaptan) met the eligibility criteria. Results suggest that all four vasopressin receptor agonists ("vaptans") significantly improve serum sodium concentration. Lixivaptan, satavaptan and tolvaptan were associated with greater rates of response versus placebo. There was no evidence of a difference between each of the vaptans compared with placebo for mortality, discontinuation and rates of hypernatraemia. No RCT evidence of treatments other than the vaptans for hyponatraemia such as oral urea, salt tablets, mannitol, loop diuretics demeclocycline or lithium was identified. Vaptans demonstrated superiority over placebo for outcomes relating to serum sodium correction. Few trials documented the potential benefit of vaptans on change in health-related quality of life as a result of treatment. There was also a lack of high-quality RCT evidence on the comparative efficacy of the vaptans and other treatment strategies for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia.

Abstract

OBJECTIVE: The objective of this review was to update a systematic review of associations between living near an animal feeding operation (AFO) and human health.

METHODS: The MEDLINE® and MEDLINE® In-Process, Centre for Agricultural Biosciences Abstracts, and Science Citation Index databases were searched. Reference lists of included articles were hand-searched. Eligible studies reported exposure to an AFO and an individual-level human health outcome. Two reviewers performed study selection and data extraction.

RESULTS: The search returned 3702 citations. Sixteen articles consisting of 10 study populations were included in the analysis. The health outcomes were lower and upper respiratory tracts, MRSA, other infectious disease, neurological, psychological, dermatological, otologic, ocular, gastrointestinal, stress and mood, and other non-infectious health outcomes. Most studies were observational and used prevalence measures of outcome. An association between Q fever risk and proximity to goat production was reported. Other associations were unclear. Risk of bias was serious or critical for most exposure-outcome associations. Multiplicity (i.e., a large number of potentially correlated outcomes and exposures assessed on the same study subjects) was common in the evidence base.

CONCLUSIONS: Few studies reported an association between surrogate clinical outcomes and AFO proximity for respiratory tract-related outcomes. There were no consistent dose-response relationships between surrogate clinical outcome and AFO proximity. A new finding was that Q fever in goats is likely associated with an increased Q fever risk in community members. The review results for the non-respiratory health outcomes were inconclusive because only a small number of studies were available or the between-study results were inconsistent.

Abstract

BACKGROUND: The antifibrotics pirfenidone and nintedanib are both approved for the treatment of idiopathic pulmonary fibrosis (IPF) by regulatory agencies and are recommended by health technology assessment bodies. Other treatments such as N-acetylcysteine are used in clinical practice but have not received regulatory approval. No head-to-head trials have been conducted to directly compare the efficacy of these therapies in IPF.

OBJECTIVE: To compare the efficacy of treatments for IPF.

METHODS: A systematic review was conducted up to April 2015. Phase II/III randomized controlled trials in adults with IPF were eligible. A Bayesian network meta-analysis (NMA) was used to compare pirfenidone, nintedanib, and N-acetylcysteine with respect to forced vital capacity (FVC) and mortality.

RESULTS: Nine studies were included in the NMA. For change from baseline in FVC, the NMA indicated that pirfenidone and nintedanib were more effective than placebo after 1 year (pirfenidone vs. placebo: difference = 0.12 liter (L), 95% credible interval [CrI] = 0.03-0.21 L; nintedanib vs. placebo: difference = 0.11 L, 95% CrI = 0.00-0.22 L). There was no evidence that N-acetylcysteine had an effect on FVC compared with placebo (N-acetylcysteine vs. placebo: difference = 0.01 L, 95% CrI = -0.15-0.17 L). Patients treated with pirfenidone also had a lower risk of experiencing a decline in percent predicted FVC of = 10% over 1 year (odds ratio [OR]: 0.58, 95% CrI = 0.40-0.88), whereas there was no conclusive evidence of a difference between nintedanib and placebo (OR: 0.65, 95% CrI = 0.42-1.02). The NMA indicated that pirfenidone reduced all-cause mortality relative to placebo over 1 year (hazard ratio [HR]: 0.52, 95% CrI = 0.28-0.92). There was no evidence of a difference in all-cause mortality between nintedanib and placebo (HR: 0.70, 95% CrI = 0.32-1.55), or N-acetylcysteine and placebo (HR: 2.00, 95% CrI=0.46-8.62).

CONCLUSIONS: Our primary analysis of the available evidence indicates that over 1 year, pirfenidone and nintedanib are effective at reducing lung-function decline, and pirfenidone may reduce the odds of experiencing a decline in percent predicted FVC of =10% compared with placebo in the first year of treatment. The results of our analysis also suggest that pirfenidone improves survival.

Abstract

OBJECTIVES: Economic evaluation (EE) is an accepted element of decision making and priority setting in healthcare. As the number of published EEs grows, so does the number of systematic reviews (SRs) of EEs. Although search methodology makes an important contribution to SR quality, search methods in reviews of EEs have not been evaluated in detail. We investigated the resources used to identify studies in recent, published SRs of EEs, and assessed whether the resources reflected recommendations.

METHODS: We searched MEDLINE for SRs of EEs published since January 2013 and extracted the following from eligible reviews: databases searched, health technology assessment (HTA) sources searched, supplementary search techniques used. Results were compared against the minimum search resources recommended by National Institute for Health and Care Excellence (NICE) (MEDLINE, Embase, NHS EED, EconLit) for economic evidence for single technology appraisals, and resource types suggested in the summary of current best evidence from SuRe Info (economic databases, general databases, HTA databases, HTA agency Web pages, gray literature).

RESULTS: Sixty-five SRs met the inclusion criteria; data were extracted from forty-two. Five reviews (12 percent) met or exceeded the NICE recommended resources. Nine reviews (21 percent) searched at least four of the five types of resource recommended by SuRe Info. Five reviews (12 percent) searched all five. Twenty-three reviews (55 percent) did not meet the NICE recommendations or four of five of the SuRe Info recommended resource types. Search reporting was frequently unclear or incorrect.

CONCLUSION: Searches conducted for the majority of recently published SRs of EEs do not meet two published approaches.

Abstract

BACKGROUND AND PURPOSE: Cost-of-illness studies often describe a single aggregate cost of a disease state. This approach is less helpful for a condition with a spectrum of outcomes like stroke. The modified Rankin Scale is the most commonly used outcome measure for stroke. We sought to describe the existing evidence on the costs of stroke according to individual modified Rankin Scale categories. This may be useful in future cost effectiveness modelling studies of interventions where cost data have not been collected, but disability outcome is known.

METHODS: Systematic review of the published literature, searching electronic databases between 2004 and 2015 using validated search filters. Results were screened to identify studies presenting costs by individual modified Rankin Scale categories.

RESULTS: Of 17,782 unique identified articles, 13 matched all inclusion criteria. In only four of these studies were costs reported by modified Rankin Scale categories. Most studies included direct medical costs only. Societal costs were assessed in two studies. Overall, studies had a high methodological and reporting quality. The heterogeneity in costing methods used in the identified studies prevented meaningful comparison of the reported cost data. Despite this limitation, the costs consistently increased with greater severity (increasing modified Rankin Scale score).

CONCLUSIONS: Few cost studies of stroke include information based on stroke recovery measured by individual modified Rankin Scale categories and the existing data are limited. To reliably capture this information, future studies are needed that preferably apply standardised costing methods to promote greater potential for use in cost-effectiveness analyses whereby direct collection of patient-level resource use has not been possible.

Abstract

BACKGROUND: Many economic evaluations of health care changes rely on quality-adjusted life year (QALY) estimates. Notably, though, the QALY approach values health states rather than changes in health states. Hence, a gain in utility of health is only indirectly valued through an ex ante preference elicitation of health states and the subsequent subtraction of health state values from one another, rather than being valued directly. There is therefore an underlying assumption that individuals, from an ex ante perspective ceteris paribus, would be indifferent between equal utility increments from health states with different baseline utilities.

OBJECTIVE: The aim of this paper is to develop a method that would allow us to measure individual-based preferences over utility increments from different baselines. We elicit our data using face-to-face interviews on a sample of UK individuals.

RESULTS: Overall, we find that gains of "equal" utility increments from different baselines are not found to be equally preferable by the individual.

CONCLUSION: The results indicate that the subtraction approach could lead to sub-optimal resource allocations and suggest that a new approach which values health changes directly would better reflect individual preferences. This paper provides the foundations for a method to achieve this.

Abstract

BACKGROUND: Allergic rhinitis is a global health problem that burdens society due to associated health care costs and its impact on health. Standardized quality (SQ®) house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is a sublingually administered allergy immunotherapy tablet for patients with persistent moderate to severe HDM allergic rhinitis despite use of allergy pharmacotherapy.

OBJECTIVE: To assess the cost-effectiveness of SQ HDM SLIT-tablet in Germany for patients suffering from HDM allergic rhinitis.

METHODS: A pharmacoeconomic analysis, based on data collected in a double-blinded, phase III randomized placebo-controlled trial (n=992), was undertaken to compare SQ HDM SLIT-tablet in addition to allergy pharmacotherapy to placebo plus allergy pharmacotherapy. Quality-adjusted life year (QALY) scores and health care resource use data recorded in the trial were applied to each treatment group and extrapolated over a nine-year time horizon. A series of scenarios were used to investigate the impact of changes on long-term patient health for both treatment groups, which was measured by annual changes in QALY scores. Deterministic and probabilistic sensitivity analyses were also performed.

RESULTS: In the base case analysis, compared with allergy pharmacotherapy, SQ HDM SLIT-tablet led to a QALY gain of 0.31 at an incremental cost of €2,276 over the nine-year time horizon, equating to an incremental cost-effectiveness ratio of €7,519. The treatment was cost-effective for all scenarios analyzed; however, results were sensitive to changes in individual parameter values during the deterministic sensitivity analysis.

CONCLUSION: SQ HDM SLIT-tablet in addition to pharmacotherapy is cost-effective compared with allergy pharmacotherapy plus placebo for the treatment of persistent moderate to severe HDM allergic rhinitis that is not well controlled by allergy pharmacotherapy.