Finding legitimacy for the role of budget impact in drug reimbursement decisions

OBJECTIVES: Research has shown that effectiveness, cost-effectiveness, and severity of illness each play a role in drug reimbursement decisions. However, the role of budget impact in such decisions is less obvious. Policy makers almost always demand a budget impact estimate yet seem reluctant to formally include budget impact as a rationing criterion. Health economists even reject budget impact as a legitimate criterion. For these reasons, it is important to examine its use in rationing decisions, and rationales underlying its use. METHODS: We trace several rationales supporting the use of budget impact through a literature review, supplemented by semistructured interviews with eleven key stakeholders involved in drug reimbursement decisions in the Netherlands. RESULTS: Budget impact arguments are used in certain instances, although policy makers appear uncomfortable with its use because well described rationales still are lacking. In addition, we identify the following rationales to support budget impact as a rationing criterion: opportunity costs, loss aversion, uncertainty and equal opportunity. CONCLUSIONS: Budget impact plays a role in drug reimbursement decisions and has rationales to support its use. However, policy makers do not easily admit that they consider budget impact and are even reluctant to explicitly use budget impact as a formal criterion. A debate would strengthen the theoretical foundation of budget impact a

The Rhodococcus erythropolis DCL14 limonene-1,2-epoxide hydrolase gene encodes an enzyme belonging to a novel class of epoxide hydrolases

AbstractRecently, we reported the purification of the novel enzyme limonene-1,2-epoxide hydrolase involved in limonene degradation by Rhodococcus erythropolis DCL14. The N-terminal amino acid sequence of the purified enzyme was used to design two degenerate primers at the beginning and the end of the 50 amino acids long stretch. Subsequently, the complete limonene-1,2-epoxide hydrolase gene (limA) was isolated from a genomic library of R. erythropolis DCL14 using a combination of PCR and colony hybridization. The limA gene encoded a 149-residue polypeptide with a deduced molecular mass of 16.5 kDa. It was functionally expressed in Escherichia coli. The amino acid sequence of limA contains neither any of the conserved regions of the α,β-hydrolase fold enzymes, to which most of the previously reported epoxide hydrolases belong, nor any of the conserved motifs present in leukotriene A4 hydrolase. The structural data presented in this paper confirm previous physical and biochemical findings [van der Werf et al. (1998) J. Bacteriol. 180, 5052–5057] that limonene-1,2-epoxide hydrolase is the first member of a new class of epoxide hydrolases

The fluid nature of water grabbing: the on-going contestation of water distribution between peasants and agribusinesses in Nduruma, Tanzania

This research article published by Springer Nature Switzerland AG., 2015This article contributes to the contemporary debate on land and water grabbing through a detailed, qualitative case study of horticultural agribusinesses which have settled in Tanzania, disrupting patterns of land and water use. In this paper we analyse how capitalist settler farms and their upstream and downstream peasant neighbours along the Nduruma river, Tanzania, expand and defend their water use. The paper is based on 3 months of qualitative field work in Tanzania. We use the echelons of rights analysis framework combined with the concept of institutional bricolage to show how this contestation takes place over the full spectrum of actual abstractions, governance and discourses. We emphasise the role different (inter)national development narratives play in shaping day-to-day contestations over water shares and rule-making. Ultimately, we emphasise that water grabbing is not a one-time event, but rather an on-going struggle over different water resources. In addition, we show how a perceived beneficial development of agribusinesses switching to groundwater allows them to avoid peasant-controlled institutions, avoiding further negotiation between the different actors and improving their image among neighbouring communities. This development illustrates how complex and obscured processes of water re-allocation can be without becoming illegal per se

An illness-focused interactive booklet to optimise management and medication for childhood fever and infections in out-of-hours primary care: study protocol for a cluster randomised trial

Background Fever is the most common reason for a child to be taken to a general practitioner (GP), especially during out-of-hours care. It is mostly caused by self-limiting infections. However, antibiotic prescription rates remain high, especially during out-of-hours care. Anxiety and lack of knowledge among parents, and perceived pressure to prescribe antibiotics amongst GPs, are important determinants of excessive antibiotic prescriptions. An illness-focused interactive booklet has the potential to improve this by providing parents with information about fever self-management strategies. The aim of this study is to develop and determine the effectiveness of an interactive booklet on management of children presenting with fever at Dutch GP out-of-hours cooperatives. Methods/design We are conducting a cluster randomised controlled trial (RCT) with 20 GP out-of-hours cooperatives randomised to 1 of 2 arms: GP access to the illness-focused interactive booklet or care as usual. GPs working at intervention sites will have access to the booklet, which was developed in a multistage process. It consists of a traffic light system for parents on how to respond to fever-related symptoms, as well as information on natural course of infections, benefits and harms of (antibiotic) medications, self-management strategies and ‘safety net’ instructions. Children < 12 years of age with parent-reported or physician-measured fever are eligible for inclusion. The primary outcome is antibiotic prescribing during the initial consultation. Secondary outcomes are (intention to) (re)consult, antibiotic prescriptions during re-consultations, referrals, parental satisfaction and reassurance. In 6 months, 20,000 children will be recruited to find a difference in antibiotic prescribing rates of 25% in the control group and 19% in the intervention group. Statistical analysis will be performed using descriptive statistics and by fitting two-level (GP out-of-hours cooperative and patient) random intercept logistic regression models. Discussion This will be the first and largest cluster RCT evaluating the effectiveness of an illness-focused interactive booklet during GP out-of-hours consultations with febrile children receiving antibiotic prescriptions. It is hypothesised that use of the booklet will result in a reduced number of antibiotic prescriptions, improved parental satisfaction and reduced intention to re-consult

Feasibility of anorectal chlamydia testing in women:a cross-sectional survey among general practitioners

BACKGROUND: Anorectal Chlamydia trachomatis (CT) may be clinically relevant for women in general practice. Although anorectal CT testing in this setting may prevent underdiagnosis and undertreatment, its feasibility is questioned as GPs currently rarely order anorectal CT tests, for yet unknown reasons. OBJECTIVE: To explore the feasibility of anorectal CT testing in women in general practice. METHODS: GPs across the Netherlands were invited directly (n = 1481) and by snowball sampling (n = 330) to join an online cross-sectional survey that asked about the acceptability of and barriers for (standard) anorectal testing in women during CT-related consultations. Data were analysed with univariable and multivariable logistic regression models. RESULTS: The questionnaire was opened by 514 respondents (28%, 514/1811) and 394 fully completed it. GPs' acceptability of anorectal testing by either self-sampling or provider-sampling was high (86%). Twenty-eight percent of GPs felt neutral, and 43% felt accepting towards standard anorectal testing. Nevertheless, 40% of GPs had never tested for anorectal CT in women, which was associated with a reported difficulty in asking about anal sex (odds ratio [OR]: 3.07, 95% confidence interval [CI]: 1.21-7.80), infrequency of anal sexual history taking (OR: 11.50, 95% CI: 6.39-20.72), low frequency of urogenital CT testing (OR 3.44, 95%-CI: 1.86-6.38) and with practicing in a non-urban area (OR: 2.27, 95% CI: 1.48-3.48). Acceptability of anorectal testing was not associated with the studied factors. CONCLUSION: This quantitative survey shows that anorectal CT testing is feasible based on its acceptability, but is likely hindered by a lower awareness of (anorectal) CT in GPs

Factors associated with dropout in a long term observational cohort of fishing communities around lake Victoria, Uganda.

BACKGROUND: Fishing communities are potentially suitable for Human immunodeficiency virus (HIV) efficacy trials due to their high risk profile. However, high mobility and attrition could decrease statistical power to detect the impact of a given intervention. We report dropout and associated factors in a fisher-folk observational cohort in Uganda. METHODS: Human immunodeficiency virus-uninfected high-risk volunteers aged 13-49 years living in five fishing communities around Lake Victoria were enrolled and followed every 6 months for 18 months at clinics located within each community. Volunteers from two of the five communities had their follow-up periods extended to 30 months and were invited to attend clinics 10-40 km (km) away from their communities. Human immunodeficiency virus counseling and testing was provided, and data on sexual behaviour collected at all study visits. Study completion was defined as completion of 18 or 30 months or visits up to the date of sero-conversion and dropout as missing one or more visits. Discrete time survival models were fitted to find factors independently associated with dropout. RESULTS: A total of 1000 volunteers (55% men) were enrolled. Of these, 91.9% completed 6 months, 85.2% completed 12 months and 76.0% completed 18 months of follow-up. In the two communities with additional follow-up, 76.9% completed 30 months. In total 299 (29.9%) volunteers missed at least one visit (dropped out). Dropout was independently associated with age (volunteers aged 13-24 being most likely to dropout), gender [men being more likely to dropout than women [adjusted hazard ratio (aHR) 1.4; 95% confidence interval (CI) 1.1-1.8)], time spent in the fishing community (those who stayed <1 year being most likely to dropout), History of marijuana use (users being more likely to dropout than non-users [1.7; (1.2-2.5)], ethnicity (non-Baganda being more likely to dropout than Baganda [1.5; (1.2-1.9)], dropout varied between the five fishing communities, having a new sexual partner in the previous 3 months [1.3 (1.0-1.7)] and being away from home for ≥2 nights in the month preceding the interview [1.4 (1.1-1.8)]. CONCLUSION: Despite a substantial proportion dropping out, retention was sufficient to suggest that by incorporating retention strategies it will be possible to conduct HIV prevention efficacy trials in this community

Who contextualises clinical epidemiological evidence?

We critically examine the discussion on the role of evidence-based medicine (EBM) in healthcare governance. We take the institutionally layered Dutch healthcare system as our case study. Here, different actors are involved in the regulation, provision and financing of healthcare services. Over the last decades, these actors have related to EBM to inform their actor specific roles. At the same time, EBM has increasingly been problematised. To better understand this problematisation, we organised focus groups and interviews. We noticed that particularly EBM’s reductionist epistemology and its uncritical use by ‘professional others’ are considered problematic. However, our analysis also reveals that something else seems to be at stake. In fact, all the actors involved underwrite EBM’s reductionist epistemology and emphasise that evidence should be contextualised. They however do so in different ways and with different contexts in mind. Moreover, the ways in which some actors contextualise evidence has consequences for the ways in which others can do the same. We therefore emphasise that behind EBM’s scientific problematisation lurks a political issue. A dispute over who should contextualise evidence how, in a layered healthcare system with interdependent actors that cater to both individual patients and the public. We urge public administration scholars and policymakers to open-up the political confrontation between healthcare actors and their sometimes irreconcilable, yet evidence-informed perspectives

Genomotyping of Pseudomonas putida strains using P. putida KT2440-based high-density DNA microarrays: implications for transcriptomics studies

Pseudomonas putida KT2440 is the only fully sequenced P. putida strain. Thus, for transcriptomics and proteomics studies with other P. putida strains, the P. putida KT2440 genomic database serves as standard reference. The utility of KT2440 whole-genome, high-density oligonucleotide microarrays for transcriptomics studies of other Pseudomonas strains was investigated. To this end, microarray hybridizations were performed with genomic DNAs of subcultures of P. putida KT2440 (DSM6125), the type strain (DSM291T), plasmid pWW0-containing KT2440-derivative strain mt-2 (DSM3931), the solvent-tolerant P. putida S12, and several other Pseudomonas strains. Depending on the strain tested, 22 to 99% of all genetic elements were identified in the genomic DNAs. The efficacy of these microarrays to study cellular function was determined for all strains included in the study. The vast majority of DSM6125 genes encoding proteins of primary metabolism and genes involved in the catabolism of aromatic compounds were identified in the genomic DNA of strain S12: a prerequisite for reliable transcriptomics analyses. The genomotypic comparisons between Pseudomonas strains were used to construct highly discriminative phylogenetic relationships. DSM6125 and DSM3931 were indistinguishable and clustered together with strain S12 in a separate group, distinct from DSM291T. Pseudomonas monteilii (DSM14164) clustered well with P. putida strains

Andreev reflection at QGP/CFL interface

In this letter we address the question of the phenomena of Andreev reflection between the cold quark-gluon plasma phase and CFL color superconductor. We show that there are two different types of reflections connected to the structure of the CFL phase. We also calculate the probability current at the interface and we show that it vanishes for energy of scattering quarks below the superconducting gap.Comment: 6 pages, 1 figure. Minor changes in the "Conclusions