Diagnosing idiopathic learning disability: a cost-effectiveness analysis of microarray technology in the National Health Service of the United Kingdom

Array based comparative genomic hybridisation (aCGH) is a powerful technique for detecting clinically relevant genome imbalance and can offer 40 to > 1000 times the resolution of karyotyping. Indeed, idiopathic learning disability (ILD) studies suggest that a genome-wide aCGH approach makes 10–15% more diagnoses involving genome imbalance than karyotyping. Despite this, aCGH has yet to be implemented as a routine NHS service. One significant obstacle is the perception that the technology is prohibitively expensive for most standard NHS clinical cytogenetics laboratories. To address this, we investigated the cost-effectiveness of aCGH versus standard cytogenetic analysis for diagnosing idiopathic learning disability (ILD) in the NHS. Cost data from four participating genetics centres were collected and analysed. In a single test comparison, the average cost of aCGH was ￡442 and the average cost of karyotyping was ￡117 with array costs contributing most to the cost difference. This difference was not a key barrier when the context of follow up diagnostic tests was considered. Indeed, in a hypothetical cohort of 100 ILD children, aCGH was found to cost less per diagnosis (￡3,118) than a karyotyping and multi-telomere FISH approach (￡4,957). We conclude that testing for genomic imbalances in ILD using microarray technology is likely to be cost-effective because long-term savings can be made regardless of a positive (diagnosis) or negative result. Earlier diagnoses save costs of additional diagnostic tests. Negative results are cost-effective in minimising follow-up test choice. The use of aCGH in routine clinical practice warrants serious consideration by healthcare providers. Copyright statement The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd, and its Licensees to permit this article (if accepted) to be published in BMJ editions and any other BMJPGL products and to exploit all subsidiary rights, as set out in our licence (bmj.com/advice/copyright.shtml). Authorship The authors included on this paper fulfil the criteria of authorship and no one who fulfils the criteria has been excluded from authorship. The authors made a substantial contribution to the conception, design, analysis and interpretation of data. They were involved in drafting the article or revising it critically for important intellectual content and approving the version to be published. Contributorship Sarah Wordsworth (Guarantor): Planning, conducting and reporting work, interpretation of data, drafting and revising article. James Buchanan: Conducting and reporting work, interpretation of data, revising article. Regina Regan: Completing costing questionnaire, providing protocol details, other costing information, interpretation of data, information about learning disability and genome imbalance and revising article. Val Davison: Completing costing questionnaire, providing protocol details, sharing overall laboratory experience and drafting article. Kim Smith: Completing costing questionnaire, providing protocol details, drafting article. Sara Dyer: Completing costing questionnaire and providing protocol details. Carolyn Campbell: Completing costing questionnaire and providing protocol details. Edward Blair: Critical appraisal of article for clinical content and revising article. Eddy Maher: Completing costing questionnaire, providing protocol details, sharing overall laboratory experience and drafting article. Jenny Taylor: Planning and facilitating work between centres. Drafting and revising article. Samantha JL Knight: Completing costing questionnaire, providing protocol details, other costing information, interpretation of data, providing information about learning disability and genome imbalance, drafting and revising article. Jenny Taylor and Samantha JL Knight contributed equally to the work presented.     

Calculation of the Average Cost per Case of Dengue Fever in Mexico Using a Micro-Costing Approach

IntroductionThe increasing burden of dengue fever (DF) in the Americas, and the current epidemic in previously unaffected countries, generate major costs for national healthcare systems. There is a need to quantify the average cost per DF case. In Mexico, few data are available on costs, despite DF being endemic in some areas. Extrapolations from studies in other countries may prove unreliable and are complicated by the two main Mexican healthcare systems (the Secretariat of Health [SS] and the Mexican Social Security Institute [IMSS]). The present study aimed to generate specific average DF cost-per-case data for Mexico using a micro-costing approach.MethodsExpected medical costs associated with an ideal management protocol for DF (denoted ´ideal costs´) were compared with the medical costs of current treatment practice (denoted ´real costs´) in 2012. Real cost data were derived from chart review of DF cases and interviews with patients and key personnel from 64 selected hospitals and ambulatory care units in 16 states for IMSS and SS. In both institutions, ideal and real costs were estimated using the program, actions, activities, tasks, inputs (PAATI) approach, a micro-costing technique developed by us.ResultsClinical pathways were obtained for 1,168 patients following review of 1,293 charts. Ideal and real costs for SS patients were US$165.72 and US$32.60, respectively, in the outpatient setting, and US$587.77 and US$490.93, respectively, in the hospital setting. For IMSS patients, ideal and real costs were US$337.50 and US$92.03, respectively, in the outpatient setting, and US$2,042.54 and US$1,644.69 in the hospital setting.ConclusionsThe markedly higher ideal versus real costs may indicate deficiencies in the actual care of patients with DF. It may be necessary to derive better estimates with micro-costing techniques and compare the ideal protocol with current practice when calculating these costs, as patients do not always receive optimal care.     

Photosynthetic Fractionation of the Stable Isotopes of Oxygen and Carbon

Isotope discrimination during photosynthetic exchange of O2 and CO2 was measured using enzyme, thylakoid, and whole cell preparations. Evolved oxygen from isolated spinach thylakoids was isotopically identical (within analytical error) to its source water. Similar results were obtained with Anacystis nidulans Richter and Phaeodactylum tricornutum Bohlin cultures purged with helium. For consumptive reactions, discrimination ([delta], where 1 + [delta]/1000 equals the isotope effect, k16/k18 or k12/k13) was determined by analysis of residual substrate (O2 or CO2). The [delta] for the Mehler reaction, mediated by ferredoxin or methylviologen, was 15.3[per mille (thousand) sign]. Oxygen isotope discrimination during oxygenation of ribulose-1,5-bisphosphate (RuBP) catalyzed by RuBP carboxylase/oxygenase (Rubisco) was 21.3[per mille (thousand) sign] and independent of enzyme source, unlike carbon isotope discrimination: 30.3[per mille (thousand) sign] for spinach enzyme and 19.6 to 23[per mille (thousand) sign] for Rhodospirillum rubrum and A. nidulans enzymes, depending on reaction conditions. The [delta] for O2 consumption catalyzed by glycolate oxidase was 22.7[per mille (thousand) sign]. The expected overall [delta] for photorespiration is about 21.7[per mille (thousand) sign]. Consistent with this, when Asparagus sprengeri Regel mesophyll cells approached the compensation point within a sealed vessel, the [delta]18O of dissolved O2 came to a steady-state value of about 21.5[per mille (thousand) sign] relative to the source water. The results provide improved estimates of discrimination factors in several reactions prominent in the global O cycle and indicate that photorespiration plays a significant part in determining the isotopic composition of atmospheric oxygen.     

Cost effectiveness analysis of clinically driven versus routine laboratory monitoring of antiretroviral therapy in Uganda and Zimbabwe

Background

Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART) have rarely been evaluated.

Methods

Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779). Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM) or laboratory and clinical monitoring (LCM); individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial.

Results

3316 (1660LCM;1656CDM) symptomatic, immunosuppressed ART-naive adults (median (IQR) age 37 (32,42); CD4 86 (31,139) cells/mm³) were followed for median 4.9 years. LCM had a mean 0.112 year (41 days) survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks). CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term.

Conclusions

There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African countries. CD4 monitoring, restricted to the second year on ART onwards, could be cost-effective with lower cost second-line therapy and development of a cheaper, ideally point-of-care, CD4 test.     

Pathogenesis of hyperphosphatemia in lactic acidosis: disparate effects of racemic (DL-) and levo (L-) lactic acid on plasma phosphorus concentration

The mechanism(s) for the hyperphosphatemia associated with lactic acidosis is unknown. Experimental lactate-induced hyperphosphatemia appears to require acidemia because we have shown that prevention of acidemia with NaHCO3 obviates increases in plasma phosphorus concentration ([P]). Since the rate of lactate metabolism (by utilizing NAD or other mechanisms) might modulate transcellular movement of phosphorus, we assessed the plasma [P] response to 3-h infusions of DL-lactic acid versus L-lactic acid. The dog metabolizes primarily the L-moiety of DL-lactic acid (thereby consuming H+), so more L-lactic acid is needed to produce the degree of acidemia attained with DL-lactic acid. Group 1 (n = 6) mongrel dogs received 12 mequiv./kg DL-lactic acid; group 2 (n = 6) 12 mequiv./kg L-lactic acid, and group 3 (n = 7) 16-19 mequiv./kg L-lactic acid. Prior to acid loading, the plasma [P] and acid-base status of the three groups were similar. After 3 h, blood pH and [HCO3] and change from base line in plasma [P], in both milligrams per decilitre and percent, were as follows: group 1: 7.05 +/- 0.02, 9 +/- 2 mM, 1.9 +/- 0.4 mg/dL, 38 +/- 10%; group 2: 7.28 +/- 0.02, 18 +/- 1, 0.9 +/- 0.3, 17 +/- 6; group 3: 7.06 +/- 0.04, 12 +/- 1, 1.1 +/- 0.3, 26 +/- 10, respectively. Thus, there was a tendency for both infusion rates of L-lactic acid to increase [P] less than DL-lactic acid, suggesting the importance of other factors in addition to pH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparing behavioral weight loss modalities: incremental cost-effectiveness of an internet-based versus an in-person condition

The objective of this study was to assess the costs associated with a group behavioral weight loss intervention and compare cost-effectiveness based on treatment delivery modality (in-person vs. Internet). A randomized controlled trial examined efficacy of a group behavioral obesity intervention across in-person and Internet treatment modalities. Participants (N = 323, 93% women, mean BMI = 35.8) from two centers were randomized to treatment modality, and contact time was matched between conditions. Primary outcome was weight loss. Cost-effectiveness measures calculated life years gained (LYG) from changes in weight at 6 months, based on excess years of life lost (YLL) algorithm and the cost of the two modalities. In-person participants had significantly greater weight losses (-8.0 ± 6.1 kg) than Internet participants (-5.5 ± 5.6 kg), whereas differences in LYG were insignificant. Estimated LYG was 0.58 (95% confidence interval: 0.45, 0.71) and 0.47 (95% confidence interval: 0.34, 0.60) for the in-person and Internet condition, respectively. Total cost of conducting the in-person condition was $706 per person and the Internet condition was $372 per person with the difference mainly due to increased travel cost of $158 per person. The incremental cost-effectiveness ratio was $2,160 per (discounted) LYG for the Internet modality relative to no intervention/no weight loss and $7,177 per (discounted) LYG for the in-person modality relative to the Internet modality. Participant time costs are recognized as an important cost of medical and behavioral interventions. When participant time costs are included in an economic evaluation of a behavioral weight loss intervention, Internet-based weight loss delivery may be a more cost-effective approach to obesity treatment.     

Scaling-up from an implementation trial to state-wide coverage: results from the preliminary Melbourne Diabetes Prevention Study

ABSTRACT: BACKGROUND: The successful Greater Green Triangle Diabetes Prevention Program (GGT DPP), a small implementation trial, has been scaled-up to the Victorian state-wide 'Life!' programme with over 10,000 individuals enrolled. The Melbourne Diabetes Prevention Study (MDPS) is an evaluation of the translation from the GGT DPP to the Life! programme. We report results from the preliminary phase (pMDPS) of this evaluation. METHODS: The pMDPS is a randomised controlled trial with 92 individuals aged 50 to 75 at high risk of developing type 2 diabetes randomised to Life! or usual care. Intervention consisted of six structured 90-minute group sessions: five fortnightly sessions and the final session at 8 months. Participants underwent anthropometric and laboratory tests at baseline and 12 months, and provided self-reported psychosocial, dietary, and physical activity measures. Intervention group participants additionally underwent these tests at 3 months. Paired t tests were used to analyse within-group changes over time. Chi-square tests were used to analyse differences between groups in goals met at 12 months. Differences between groups for changes over time were tested with generalised estimating equations and analysis of covariance. RESULTS: Intervention participants significantly improved at 12 months in mean body mass index ([MINUS SIGN]0.98 kg/m2, standard error (SE) = 0.26), weight ([MINUS SIGN]2.65 kg, SE = 0.72), waist circumference ([MINUS SIGN]7.45 cm, SE = 1.15), and systolic blood pressure ([MINUS SIGN]3.18 mmHg, SE = 1.26), increased high-density lipoprotein-cholesterol (0.07 mmol/l, SE = 0.03), reduced energy from total ([MINUS SIGN]2.00%, SE = 0.78) and saturated fat ([MINUS SIGN]1.54%, SE = 0.41), and increased fibre intake (1.98 g/1,000 kcal energy, SE = 0.47). In controls, oral glucose at 2 hours deteriorated (0.59 mmol/l, SE = 0.27). Only waist circumference reduced significantly ([MINUS SIGN]4.02 cm, SE = 0.95).Intervention participants significantly outperformed controls over 12 months for body mass index and fibre intake. After baseline adjustment, they also showed greater weight loss and reduced saturated fat versus total energy intake.At least 5% weight loss was achieved by 32% of intervention participants versus 0% controls. CONCLUSIONS: pMDPS results indicate that scaling-up from implementation trial to state-wide programme is possible. The system design for Life! was fit for purpose of scaling-up from efficacy to effectiveness.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12609000507280.     

Physicochemical analysis of phasic menstrual cycle effects on acid-base balance

In accordance with Stewart's physicochemical approach, the three independent determinants of plasma hydrogen ion concentration ([H(+)]) were measured at rest and during exercise in the follicular (FP) and luteal phase (LP) of the human menstrual cycle. Healthy, physically active women with similar physical characteristics were tested during either the FP (n = 14) or LP (n = 14). Arterialized blood samples were obtained at rest and after 5 min of upright cycling at both 70 and 110% of the ventilatory threshold (T(Vent)). Measurements included plasma [H(+)], arterial carbon dioxide tension (Pa(CO(2))), total weak acid ([A(Tot)]) as reflected by total protein, and the strong-ion difference ([SID]). The transition from rest to exercise in both groups resulted in a significant increase in [H(+)] at 70% T(Vent) versus rest and at 110% T(Vent) versus both rest and 70% T(Vent). No significant between-group differences were observed for [H(+)] at rest or in response to exercise. At rest in the LP, [A(Tot)] and Pa(CO(2)) were significantly lower (acts to decrease [H(+)]) compared with the FP. This effect was offset by a reduction in [SID] (acts to increase [H(+)]). After the transition from rest to exercise, significantly lower [A(Tot)] during the LP was again observed. Although the [SID] and Pa(CO(2)) were not significantly different between groups, trends for changes in these two variables were similar to changes in the resting state. In conclusion, mechanisms regulating [H(+)] exhibit phase-related differences to ensure [H(+)] is relatively constant regardless of progesterone-mediated ventilatory changes during the LP.     

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial

Background

Some observational studies have suggested that higher prenatal Vitamin D intake may be associated with improved health outcomes in childhood. However there have been mixed results in this area with some negative studies, especially for effects on atopic and respiratory outcomes. We examined the effect of prenatal Vitamin D on healthcare utilisation in the first three years of life.

Methods

In an ethnically stratified randomised controlled trial conducted at St Mary’s Hospital London, 180 women at 27 weeks gestation were allocated to no Vitamin D, 800 IU ergocalciferol daily until delivery, or a single oral bolus of 200,000 IU cholecalciferol. Participants were randomised in blocks of 15 using computer-generated numbers and investigators were blinded to group assignment. Supplementation increased maternal and cord blood 25(OH) vitamin D concentrations, but levels remained lower than current recommendations. Primary health economic outcome was overall cost of unscheduled healthcare utilisation in the first three years of life as documented in the child’s electronic health record. Secondary outcomes included cost attributable to: primary and secondary healthcare visits, respiratory and atopic complaints, cost in years 1, 2 and 3 of life and cost and frequency of prescribed medication. All costs were calculated as pounds sterling. Differences between groups were analysed using unpaired t-test or Mann-Whitney U test, and analysis of variance for adjusted analyses.

Results

We assessed 99/180 (55%) complete electronic health records, control (n = 31), daily (n = 36) and bolus (n = 32). We found no difference in total healthcare utilisation costs between the control and daily (mean difference in costs in pounds sterling 1.02, 95%CI -1.60, 1.65; adjusted 1.07, 95%CI -1.62, 1.86) or control and bolus groups (mean difference -1.58, 95%CI -2.63, 1.06; adjusted –1.40, 95%CI -2.45, 1.24). There were no adverse effects of supplementation reported during the trial.

Conclusions

We found no evidence that prenatal vitamin D supplementation from 27 weeks gestation to delivery, at doses which failed to completely correct maternal vitamin D deficiency, influence overall healthcare utilisation in children in the first 3 years.

Trial Registration

Controlled-Trials.com ISRCTN68645785     

Evening light exposure to computer screens disrupts human sleep,biological rhythms,and attention abilities

The use of electronic devices with light-emitting screens has increased exponentially in the last decade. As a result, humans are almost continuously exposed to unintentional artificial light. We explored the independent and combined effects of two aspects of screen illumination, light wavelength, and intensity, on sleep, its biological regulation, and related functional outcomes. The 2 × 2 repeated-measure design included two independent variables: screen light intensity (low ([LI] versus high [HI]) and wavelength (short [SWL] versus long [LWL]). Nineteen participants (11F, 8M; mean age 24.3 [±2.8] years) underwent four light conditions, LI/SWL, HI/SWL, LI/LWL, and HI/LWL, in counterbalanced order. Each light exposure lasted for two hours (21:00–23:00), following which participants underwent an overnight polysomnography. On each experimental night, oral temperature and urine samples (for melatonin analysis) were collected at multiple time points. Each morning, participants filled out questionnaires and conducted a computerized attention task. Irrespective of light intensity, SWL illumination significantly disrupted sleep continuity and architecture and led to greater self-reported daytime sleepiness. SWL light also altered biological rhythms, subduing the normal nocturnal decline in body temperature and dampening nocturnal melatonin secretion. Light intensity seemed to independently affect sleep as well, but to a lesser degree. Both light intensity and wavelength negatively affected morning attention. In sum, light wavelength seems to have a greater influence than light intensity on sleep and a wide-range of biological and behavioral functions. Given the widespread use of electronic devices today, our findings suggest that screen light exposure at evening may have detrimental effects on human health and performance.     

Costes directos sanitarios y resultados clínicos tras el inicio del tratamiento con insulina en pacientes con diabetes mellitus tipo 2 en España: datos de 24 meses de seguimiento del estudio INSTIGATE

Background and objectiveThe INSTIGATE study assessed healthcare costs and clinical outcomes in patients with type 2 diabetes mellitus starting insulin therapy in Spain over a 24-month follow up period.Material and methodsThis was an observational, non-interventional, prospective, multicenter study. Costs incurred in the previous 6 months were assessed at each visit.ResultsA total of 172 patients with a mean body mass index of 29.6 kg/m², a mean [standard deviation] duration of diabetes of 10.9 [7.0] years and a hemoglobin A_1c value of 9.2% [1.5%] were followed up for at least 12 and up to 24 months. Direct costs were assessed from the perspective of the Spanish healthcare system. Long/intermediate-acting insulin alone was started in 116 patients (67.4%). After 6, 12, and 24 months of insulin treatment, mean [SD] intraindividual changes from baseline in hemoglobin A_1c were -1.9% [1.65%], -1.6 [1.73%], and -1.5% [1.76%] respectively. Mean (median) total diabetes-related healthcare costs per patient increased from €659 (€527) to €1.085 (€694) 6 months after insulin initiation, decreased to €646 (€531) after 12 months, and increased again after 24 months to €667(€539). Insulin/oral antidiabetics, primary/specialized care, and blood glucose monitoring accounted for 41%, 26%, and 19% of total cost at 24 months respectively.ConclusionsClinical parameters of these patients with type 2 diabetes mellitus improved following insulin initiation. After a temporary increase, direct healthcare costs of diabetes care returned to baseline values at the end of the follow-up period.     

Effects of elevated CO2 concentration on seed production in C3 annual plants

The response of seed production to CO(2) concentration ([CO(2)]) is known to vary considerably among C(3) annual species. Here we analyse the interspecific variation in CO(2) responses of seed production per plant with particular attention to nitrogen use. Provided that seed production is limited by nitrogen availability, an increase in seed mass per plant results from increase in seed nitrogen per plant and/or from decrease in seed nitrogen concentration ([N]). Meta-analysis reveals that the increase in seed mass per plant under elevated [CO(2)] is mainly due to increase in seed nitrogen per plant rather than seed [N] dilution. Nitrogen-fixing legumes enhanced nitrogen acquisition more than non-nitrogen-fixers, resulting in a large increase in seed mass per plant. In Poaceae, an increase in seed mass per plant was also caused by a decrease in seed [N]. Greater carbon allocation to albumen (endosperm and/or perisperm) than the embryo may account for [N] reduction in grass seeds. These differences in CO(2) response of seed production among functional groups may affect their fitness, leading to changes in species composition in the future high-[CO(2)] ecosystem.     

Effectiveness of knowledge brokering and recommendation dissemination for influencing healthcare resource allocation decisions: A cluster randomised controlled implementation trial

BackgroundImplementing evidence into clinical practice is a key focus of healthcare improvements to reduce unwarranted variation. Dissemination of evidence-based recommendations and knowledge brokering have emerged as potential strategies to achieve evidence implementation by influencing resource allocation decisions. The aim of this study was to determine the effectiveness of these two research implementation strategies to facilitate evidence-informed healthcare management decisions for the provision of inpatient weekend allied health services.Methods and findingsThis multicentre, single-blinded (data collection and analysis), three-group parallel cluster randomised controlled trial with concealed allocation was conducted in Australian and New Zealand hospitals between February 2018 and January 2020. Clustering and randomisation took place at the organisation level where weekend allied health staffing decisions were made (e.g., network of hospitals or single hospital). Hospital wards were nested within these decision-making structures. Three conditions were compared over a 12-month period: (1) usual practice waitlist control; (2) dissemination of written evidence-based practice recommendations; and (3) access to a webinar-based knowledge broker in addition to the recommendations. The primary outcome was the alignment of weekend allied health provision with practice recommendations at the cluster and ward levels, addressing the adoption, penetration, and fidelity to the recommendations. The secondary outcome was mean hospital length of stay at the ward level. Outcomes were collected at baseline and 12 months later. A total of 45 clusters (n = 833 wards) were randomised to either control (n = 15), recommendation (n = 16), or knowledge broker (n = 14) conditions. Four (9%) did not provide follow-up data, and no adverse events were recorded. No significant effect was found with either implementation strategy for the primary outcome at the cluster level (recommendation versus control β 18.11 [95% CI −8,721.81 to 8,758.02] p = 0.997; knowledge broker versus control β 1.24 [95% CI −6,992.60 to 6,995.07] p = 1.000; recommendation versus knowledge broker β −9.12 [95% CI −3,878.39 to 3,860.16] p = 0.996) or ward level (recommendation versus control β 0.01 [95% CI 0.74 to 0.75] p = 0.983; knowledge broker versus control β −0.12 [95% CI −0.54 to 0.30] p = 0.581; recommendation versus knowledge broker β −0.19 [−1.04 to 0.65] p = 0.651). There was no significant effect between strategies for the secondary outcome at ward level (recommendation versus control β 2.19 [95% CI −1.36 to 5.74] p = 0.219; knowledge broker versus control β −0.55 [95% CI −1.16 to 0.06] p = 0.075; recommendation versus knowledge broker β −3.75 [95% CI −8.33 to 0.82] p = 0.102). None of the control or knowledge broker clusters transitioned to partial or full alignment with the recommendations. Three (20%) of the clusters who only received the written recommendations transitioned from nonalignment to partial alignment. Limitations include underpowering at the cluster level sample due to the grouping of multiple geographically distinct hospitals to avoid contamination.ConclusionsOwing to a lack of power at the cluster level, this trial was unable to identify a difference between the knowledge broker strategy and dissemination of recommendations compared with usual practice for the promotion of evidence-informed resource allocation to inpatient weekend allied health services. Future research is needed to determine the interactions between different implementation strategies and healthcare contexts when translating evidence into healthcare practice.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12618000029291.

In a cluster randomized controlled implementation trial, Dr. Mitchell N Sarkies and colleagues examine the effectiveness of knowledge brokering and recommendation dissemination in influencing healthcare resource allocation decisions in Australia and New Zealand.     

Cost-Effectiveness of a Home Based Intervention for Secondary Prevention of Readmission with Chronic Heart Disease

The aim of this study is to consider the cost-effectiveness of a nurse-led, home-based intervention (HBI) in cardiac patients with private health insurance compared to usual post-discharge care. A within trial analysis of the Young @ Heart multicentre, randomized controlled trial along with a micro-simulation decision analytical model was conducted to estimate the incremental costs and quality adjusted life years associated with the home based intervention compared to usual care. For the micro-simulation model, future costs, from the perspective of the funder, and effects are estimated over a twenty-year time horizon. An Incremental Cost-Effectiveness Ratio, along with Incremental Net Monetary Benefit, is evaluated using a willingness to pay threshold of $50,000 per quality adjusted life year. Sub-group analyses are conducted for men and women across three age groups separately. Costs and benefits that arise in the future are discounted at five percent per annum. Overall, home based intervention for secondary prevention in patients with chronic heart disease identified in the Australian private health care sector is not cost-effective. The estimated within trial incremental net monetary benefit is -$3,116 [95%CI: -11,145, $4,914]; indicating that the costs outweigh the benefits. However, for males and in particular males aged 75 years and above, home based intervention indicated a potential to reduce health care costs when compared to usual care (within trial: -$10,416 [95%CI: -$26,745, $5,913]; modelled analysis: -$1,980 [95%CI: -$22,843, $14,863]). This work provides a crucial impetus for future research to understand for whom disease management programs are likely to benefit most.     

Cost-effectiveness of early versus standard antiretroviral therapy in HIV-infected adults in Haiti

Background

In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial.

Methods and Findings

Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS).

Conclusions

Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00120510","term_id":"NCT00120510"}}NCT00120510 Please see later in the article for the Editors'' Summary     

Depression case management by practice nurses in primary care: an audit

Introduction Depression is a common and debilitating condition. A body of evidence exists about improving depression outcomes in primary care, using collaborative care models. Such approaches, however, have not been routinely adopted within general practice settings. In this paper we outline the results of an audit of an enhanced care initiative that trained practice nurses to deliver such approaches.Method An audit of symptom outcome and satisfaction was conducted in depression case-management clinics run by practice nurses. Results were then benchmarked against appropriate randomised trial data. The cost of practice nurse time devoted to the delivery of the service was estimated by multiplying time by unit cost.Results A mean change of 9.07 (standard deviation (SD) 6.67, 95% confidence interval (CI) 7.93-10.22, P < 0.001) points on the Patient Health Questionnaire (PHQ9) score was observed in those who were using/had used the service. Clinical change demonstrated a shift from moderate-to-severe to mild depression. The results reflect the changes seen in randomised controlled trial data from similar interventions in similar samples, and are superior to expected treatment as usual outcomes. Overall, respondents were 'very satisfied' with the service on offer. The mean cost of practice nurse time was estimated at ￡45 per patient.Discussion While acknowledging the limitations of audit data, practice nurses in general practice appear to be able to offer effective and acceptable case management to patients experiencing depression.     

Flow kinetics of nylon open-tubular and beaded immobilized glucose oxidase reactors

Equations describing the flow kinetics of immobilized glucose oxidase in open nylon tubes and in tubes filled with solid glass spheres were experimentally determined. Reactors of three different tube (dt) and bead (db) diameters were tested using various linear flow rates (vf) and glucose concentrations ([S]). The kinetics of the open-tubular reactors were described by [P] = 1.5.10(-3) [S] L0.86 vf-0.78 dt-0.9 and the kinetics of the beaded-tubular reactors by [P] = 5.10(-3) [S] L0.98 vf-0.75 dt-1.0 (db/dt)2.7, where [P] equals the concentration of H2O2 formed. The aspect ratio, db/dt, is the critical design factor for beaded reactors.     

The impact of electronic mail versus print delivery of an exercise program on muscular strength and aerobic capacity in people with type 2 diabetes

Previous research indicates that the Internet, electronic mail (e-mail), and printed materials can be used to deliver interventions to improve physical activity in people with type 2 diabetes. However, no studies have been conducted investigating the effect of e-mail or print delivery of an exercise program on muscular strength and aerobic capacity in people with type 2 diabetes. The purpose of this clinical trial was to investigate the impact of e-mail vs. print delivery of an exercise program on muscular strength and aerobic capacity in people with type 2 diabetes. Nineteen participants with type 2 diabetes were allocated to either a group that was delivered a prescribed exercise program using e-mail (e-mail group, n = 10) or a group that was delivered the same prescribed exercise program in print form (print group, n = 9). Chest press and leg press estimated one-repetition maximum (1-RM) scores as well as estimated peak oxygen uptake ([latin capital V with dot above]O2peak) were measured at baseline and follow-up. Intention-to-treat analysis indicated significant improvements in chest press (mean = 7.00 kg, p = 0.001, effect size = 2.22) and leg press (mean = 19.32 kg, p = 0.002, effect size = 1.98) 1-RM scores and [latin capital V with dot above]O2peak (mean = 9.38 mL of oxygen uptake per kilogram of body mass per minute, p = 0.01, effect size = 1.45) within the e-mail group. Within the print group, significant improvements in chest press (mean = 9.13 kg, p = 0.01, effect size = 1.49) and leg press (mean = 16.68 kg, p = 0.01, effect size = 1.31) 1-RM scores and [latin capital V with dot above]O2peak (mean = 5.14 ml of oxygen uptake per kilogram of body mass per minute, p = 0.03, effect size = 1.14) were found. No significant between-group differences in improvements were found. Clinicians can deliver a prescribed exercise program, either by e-mail or in print form, to significantly improve muscular strength and aerobic capacity in people with type 2 diabetes, and expect similar outcomes.