Pragmatic Outcome Research Articles

Effect of electromagnetic radiation on redox status, acetylcholine esterase activity and cellular damage contributing to the diminution of the brain working memory in rats

Behavioral impairments are the most pragmatic outcome of long-term mobile uses but the underlying causes are still poorly understood. Therefore, the Aim of the present study to determine the possible mechanism of mobile induced behavioral alterations by observing redox status, cholinesterase activity, cellular, genotoxic damage and cognitive alterations in rat hippocampus. This study was carried out on 24 male Wistar rats, randomly divided into four groups (n = 6 in each group): group I consisted of sham-exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation (900 MHz) at different time duration 1 h, 2 h, and 4 h respectively for 90 days. After 90 days of exposure, rats were assessing learning ability by using T-Maze. A significantly increased level of malondialdehyde (MDA) with concomitantly depleted levels of superoxide dismutase (SOD), catalase (CAT) and redox enzymes (GSH, GPX, GR, GST, G-6PDH) indicated an exposure of mobile emitted EMR induced oxidative stress by the depleted redox status of brain cells. The depletion in the acetylcholinesterase (AChE) level reveals altered neurotransmission in brain cells. Resultant cellular degeneration was also observed in the radiation-exposed hippocampus. Conclusively, the present study revealed that microwave radiation induces oxidative stress, depleted redox status, and causes DNA damage with the subsequent reduction in working memory in a time-dependent manner. This study provides insight over the associative reciprocity between redox status, cellular degeneration and reduced cholinergic activity, which presumably leads to the behavioral alterations following mobile emitted electromagnetic radiation.

Executive Functions, Pragmatic Skills, and Mental Health in Children With Congenital Cytomegalovirus (CMV) Infection With Cochlear Implants: A Pilot Study

Congenital cytomegalovirus (cCMV) infection is the most common cause of progressive hearing impairment. In our previous study around 90% of children with a cCMV infection and CI had severely damaged balance functions (Karltorp et al., 2014). Around 20% had vision impairment, 15% were diagnosed with Autism-Spectrum-Disorder, and 20% with ADHD. One clinical observation was that children with cCMV infection had problems with executive functioning (EF), while controls with a genetic cause of deafness (Connexin 26 mutations; Cx26) did not have similar difficulties. A follow-up study was therefore initiated with the main objective to examine EF and pragmatic skills in relation to mental health in children with a cCMV infection and to draw a comparison with matched controls with Cx26 mutations (age, sex, hearing, non-verbal cognitive ability, vocabulary, and socioeconomic status level). Ten children with a cCMV infection and CI (4.8–12:9 years) and seven children with CI (4:8–12:8 years) participated in the study, which had a multidisciplinary approach. Executive functioning was assessed both with formal tests targeting working memory and attention, parent and teacher questionnaires, and a systematic observation by a blinded psychologist during one test situation. Pragmatics and mental health were investigated with parent and teacher reports. In addition, the early language outcome was considered in non-parametric correlation analyses examining the possible relationships between later EF skills, pragmatics, and mental health. Children with cCMV had a statistically significant worse pragmatic outcome and phonological working memory than controls despite their groups having similar non-verbal cognitive ability and vocabulary. However, there were no statistical differences between the groups regarding their EF skills in everyday settings and mental health. There were associations between early language outcomes and later EF skills and pragmatics in the whole sample.Conclusion: Children with a cCMV infection are at risk of developing learning difficulties in school due to difficulties with phonological working memory and pragmatic skills in social interactions.

Diagnostic stability and long-term symptomatic and functional outcomes in first-episode antipsychotic-naïve patients with schizophrenia

ObjectiveIn a prospective cohort design, we investigated: i) diagnostic stability of initially antipsychotic-naïve schizophrenia patients, ii) symptom severity including symptomatic remission, and iii) functional remission including full recovery. MethodsWe included 143 antipsychotic-naïve patients with first-episode schizophrenia or schizoaffective disorder. After 4–18 years, we clinically re-evaluated diagnosis, symptom severity and functioning for 70 patients. From the nationwide Danish registers, we extracted pragmatic outcome measures for 142 patients. We examined associations between baseline variables (age at diagnosis, sex, and premorbid intelligence) and long-term outcome status (symptomatic and functional remission). ResultsAt 4–18 years follow-up, 80% met the criteria for schizophrenia or schizoaffective disorder, however, despite the high diagnostic stability 53% met the criteria of symptomatic and/or functional remission. Symptomatic remission characterized 34% of the patients and was associated with female sex, better premorbid intelligence, and a younger age at schizophrenia diagnosis. Functional remission characterized 41% of the patients and 17% of patients met criteria for full recovery both of which were associated with female sex. The clinically re-evaluated patients did not differ from the drop-outs on key register-based variables. ConclusionWe confirm the emerging evidence of a decreasing long-term diagnostic stability of schizophrenia, and a protective role of female sex. The association between premorbid intelligence and symptomatic remission underscores the pertinence of including cognitive deficits in the diagnostic category of schizophrenia. The association between younger age at diagnosis and symptomatic remission may reflect positive effects of early detection or a drift in the interpretation of the diagnostic classification system.

Matrix Converter Control Strategies and Modulation Techniques

The matrix converter is an variety of restrained semiconductor changeovers that interfaces straightforwardly to the three-phase (3-Ø) supply to the 3-Ø load. This paper presents the cutting edge see in the improvement of this converter, beginning with a concise recorded survey. A significant piece of this paper is discourse of the most significant modulation and control techniques grew as of late. Uncommon consideration is apt to current contemporary technologies cultivated to take care of commutation issue. certain new varieties of energy bidirectional changeovers associated in a exclusive module and certain pragmatic outcome akin to the feasible appeal of this methods like over voltage safety, accustom of filtrate, and ride-through skill are further presented. Ultimately, this paper consists of simulation blocks and their corresponding results and also relation between different control techniques. Over the most recent couple of years, an expansion in research achievement obsolete watched, carrying this analysis confining to the modern requisition.

Days alive and out of hospital after fast-track total hip and knee arthroplasty: an observational cohort study in 16 137 patients

BackgroundDays alive and out of hospital (DAH) has been proposed as a pragmatic outcome measure of surgical quality. However, there is a lack of procedure specific data or data within an optimised fast-track protocol. Furthermore, information about influence of follow-up duration and types of complications on DAH is limited. MethodsObservational multicentre cohort study of patients undergoing fast-track total hip (THA) and knee arthroplasty (TKA). Prospective information on comorbidity and complete 90 days follow-up was undertaken through the Danish National Patient Register and chart review. ResultsFor 16 137 procedures, of which 18.6% were high-risk (≥2 preoperative risk factors), the median length of stay was 2 days (inter-quartile range [IQR], 2–3), and 30- and 90-day readmission rates were 5.7% and 8.1%, respectively. Median DAH30 and DAH90 days were 27 (26–28) and 87 (85–88) vs 28 (27–28) and 88 (87–89) (P<0.001) in high-vs low-risk patients, respectively. The fraction with DAH ≤25 at 30 days and DAH ≤85 at 90 days was increased in high-vs low-risk patients: 23.3% vs 6.8% (odds ratio [OR]=4.16; 95% confidence interval [CI], 3.73–4.65) and 26.0% vs 8.6% (OR=3.75; 95% CI, 3.38–4.16). There were relatively fewer ‘surgical’ complications in high- vs low-risk patients with DAH30 ≤25 (14.6% vs 25.8%) (OR=0.49; 95% CI, 0.37–0.65) and DAH90 ≤85 (16.9% vs 31.89%) (OR=0.43; 95% CI, 0.34–0.56). About 2% of patients had readmissions, but DAH was >25 and >85 at 30 and 90 days after operation, respectively. ConclusionMedian DAH in fast-track THA/TKA patients is 28 at 30 days and 88 at 90 days after surgery. DAH in high-risk patients was only slightly reduced compared with low-risk patients, but they have relatively more ‘medical’ complications.

A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia

BackgroundNovel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument’s ability to detect clinically meaningful treatment benefit for this context of use.MethodsOur mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30.ResultsUnique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context.ConclusionSupplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning.

Administrative claims data to support pragmatic clinical trial outcome ascertainment on cardiovascular health.

Health plan administrative claims data present a cost-effective complement to traditional trial-specific ascertainment of clinical events typically conducted through patient report or a single health system electronic health record. We aim to demonstrate the value of health plan claims data in improving the capture of endpoints in longitudinal pragmatic clinical trials. This retrospective cohort study paralleled the design of the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) trial designed to compare the effectiveness of two doses of aspirin. We applied the ADAPTABLE identification query in claims data from Anthem, an American health insurance company, and identified health plan members who met the ADAPTABLE trial criteria. Among the ADAPTABLE eligible members, we selected overlapping members with PCORnet Clinical Data Research Networks in the 2 years prior to the index date (1 April 2014). PCORnet Clinical Data Research Networks consist of network partners (or healthcare systems) that store their electronic health record data in the same format to support multi-institutional research. ADAPTABLE outcome events-cardiovascular hospitalizations including admissions for myocardial infarction, stroke, or cardiac procedures; hospitalizations for major bleeding; and in-hospital deaths-were evaluated for a 2-year follow-up period. Events were classified as within or outside PCORnet Clinical Data Research Networks using facility identifiers affiliated with each hospital stay. Patient characteristics were examined with descriptive statistics, and incidence rates were reported for available Clinical Data Research Networks and claims data. Among 884,311 ADAPTABLE eligible health plan members, 11,101 patients overlapped with PCORnet Clinical Data Research Networks. Average age was 70 years, 71% were male, and average follow-up was 20.7 months. Patients had 1521 cardiovascular hospitalizations (571 (37.5%) occurred outside PCORnet Clinical Data Research Networks), 710 for major bleeding (296 (41.7%) outside PCORnet Clinical Data Research Networks), and 196 in-hospital deaths (67 (34.2%) outside PCORnet Clinical Data Research Networks). Incidence rates (events per1000 patient-months) differed between available network partners and claims data: cardiovascular hospitalizations, 4.1 (95% confidence interval: 3.9, 4.4) versus 6.6 (95% confidence interval: 6.3, 7.0), major bleeding, 1.8 (95% confidence interval: 1.6, 2.0) versus 3.1 (95% confidence interval: 2.9, 3.3), and in-hospital death, 0.56 (95% confidence interval: 0.47, 0.67) versus 0.85 (95% confidence interval: 0.74, 0.98), respectively. This study demonstrated the value of supplementing longitudinal site-based clinical studies with administrative claims data. Our results suggest that claims data together with network partner electronic health record data constitute an effective vehicle to capture patient outcomes since >30% of patients have non-fatal and fatal events outside of enrolling sites.

Morality in Scientific Practice: The Relevance and Risks of Situated Scientific Knowledge in Application-Oriented Social Research

After decades of epistemological inquiry on the social construction of science, we have observed a renewed consensus on empiricism in application-oriented social sciences and a growing trust in evidence-based practice and decision-making. Drawing on the long-standing debate on value-ladenness, evidence and normativity in sciences, this article theoretically discusses and empirically illustrates the Life-World origins of methods in a domain of inquiry strongly characterized by an empiricist epistemic culture and a normative stance: Children and Media Studies. Adopting a reflexive approach to their own research in such an epistemologically underexplored field, the authors analyze a standard research instrument (the codebook for content analysis) and two procedures (operational definitions and intercoder agreement). The analysis illustrates how background assumptions (e.g., moral suitability) shape the research method and how the procedures routinely conceal this work of shaping. In the discussion the authors cast light on the role scientific procedures play in the naturalization of a given moral order, and put forward the question of whether and how this “morality-building” feature of methods should be taken into account in the assessment of their appropriateness. In the conclusion the authors advance that the situated nature of scientific knowledge, rather than discrediting its relevance, is what makes it relevant, here and now, for the larger community the research may impact on. The authors discuss the risks of such a pragmatic outcome and propose the adoption of an oscillating epistemic stance as a way to cope with them.

Clinical SLEDAI-2K zero may be a pragmatic outcome measure in SLE studies

ABSTRACTObjectives: Development of therapies for systemic lupus erythematosus (SLE) has in part been limited by the lack of suitable outcome measures in clinical trials. In the present post-hoc analysis of two clinical trials of belimumab, we investigated two potential outcomes, the Lupus Low Disease Activity State (LLDAS) and clinical SLE disease activity index 2000 (cSLEDAI-2K) zero, in relation to SLE responder index 4 (SRI-4).Methods: A total of 1684 SLE patients from the BLISS-52 (n = 865) and BLISS-76 (n = 819) trials were surveyed. Physician’s Global Assessment (PGA) scores <0.5 (3-point scale) were used for comparisons. We used the chi-square test for comparisons and the phi coefficient for correlations.Results: At week 52, LLDAS was achieved by 8.6% of patients, cSLEDAI-2K = 0 by 34.5% and SRI-4 by 45.1%. cSLEDAI-2K = 0 showed the strongest correlation with PGA <0.5 (rφ = 0.36, P < 0.001). cSLEDAI-2K = 0 unveiled the superiority of belimumab 10 mg/kg over placebo (P = 0.003) with a magnitude which was comparable to that of SRI-4 (P < 0.001). LLDAS displayed a more moderate separation (P = 0.033).Conclusions: LLDAS was a stringent measure. cSLEDAI-2K = 0 showed the strongest correlation with the clinician-based evaluation. Being based on the SLEDAI-2K only, cSLEDAI-2K = 0 may be considered a more pragmatic outcome measure in SLE studies compared with composite tools.Trial registration: ClinicalTrials.gov identifier: NCT00424476.Trial registration: ClinicalTrials.gov identifier: NCT00410384.

Renal Outcomes in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL)

Background: EXSCEL was a multinational, randomized, blinded, placebo-controlled, pragmatic CV outcome trial of once-weekly exenatide on the background of usual care. We report exenatide’s impact on estimated glomerular filtration rate (eGFR), new macroalbuminuria and 2 renal composites from a prespecified analysis plan. Methods: Opportunistic local laboratory data were collected. Overall least squares mean difference (LSMD) eGFR (95% confidence interval [95% CI]) was calculated for 13844 patients with baseline and ≥1 follow-up value. Effect on new macroalbuminuria was estimated with a Cox regression model. Effects on renal composites were estimated with interval censored time to event models, with and without covariate adjustment (demographics and disease characteristics). Results: Intention-to-treat analyses showed no significant difference in eGFR levels with exenatide (LSMD +0.21 [-0.27, 0.70] mL/min.1.73m2, p=0.39). New macroalbuminuria occurred in 2.2% and 2.5% of the exenatide and placebo groups (p=0.19). There was a 15% lower renal composite 2 adjusted risk with exenatide (p=0.027) (Table). Conclusions: A composite of 40% eGFR decline, renal replacement, renal death or new macroalbuminuria was significantly reduced in an adjusted analysis by the addition of exenatide in a broad range of people with type 2 diabetes. Other renal outcomes were numerically but not statistically improved with exenatide. Disclosure M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. R.J. Mentz: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck &amp; Co., Inc.. P. Merrill: None. J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson &amp; Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck &amp; Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp &amp; Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company. S.G. Goodman: Research Support; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Bristol-Myers Squibb Company. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; Pfizer Inc.. Consultant; Self; Pfizer Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; CSL Behring. N. Iqbal: Employee; Self; AstraZeneca. N. Jakuboniene: None. B.G. Katona: Employee; Self; AstraZeneca. Y. Lokhnygina: None. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck &amp; Co., Inc.. Other Relationship; Self; Pfizer Inc.. A.P. Maggioni: None. P.K. Ohman: Employee; Self; AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. A. Ramachandran: None. T. Tankova: None. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck &amp; Co., Inc., Abbott. A.F. Hernandez: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck &amp; Co., Inc.. Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation. R.R. Holman: Research Support; Self; AstraZeneca, Merck &amp; Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck &amp; Co., Inc.. Other Relationship; Self; AstraZeneca.

Mapping the evidence on pharmacological interventions for non-affective psychosis in humanitarian non-specialised settings: a UNHCR clinical guidance

BackgroundPopulations exposed to humanitarian emergencies are particularly vulnerable to mental health problems, including new onset, relapse and deterioration of psychotic disorders. Inadequate care for this group may lead to human rights abuses and even premature death. The WHO Mental Health Gap Action Programme Intervention Guide (mhGAP-IG), and its adaptation for humanitarian settings (mhGAP-HIG), provides guidance for management of mental health conditions by non-specialised healthcare professionals. However, the pharmacological treatment of people with non-affective psychosis who do not improve with mhGAP first-line antipsychotic treatments is not addressed. In order to fill this gap, UNHCR has formulated specific guidance on the second-line pharmacological treatment of non-affective psychosis in humanitarian, non-specialised settings.MethodsFollowing the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a group of international experts performed an extensive search and retrieval of evidence on the basis of four scoping questions. Available data were critically appraised and summarised. Clinical guidance was produced by integrating this evidence base with context-related feasibility issues, preferences, values and resource-use considerations.ResultsWhen first-line treatments recommended by mhGAP (namely haloperidol and chlorpromazine) are not effective, no other first-generation antipsychotics are likely to provide clinically meaningful improvements. Risperidone or olanzapine may represent beneficial second-line options. However, if these second-line medications do not produce clinically significant beneficial effects, there are two possibilities. First, to switch to the alternative (olanzapine to risperidone or vice versa) or, second, to consider clozapine, provided that specialist supervision and regular laboratory monitoring are available in the long term. If clinically relevant depressive, cognitive or negative symptoms occur, the use of a selective serotonin reuptake inhibitor may be considered in addition or as an alternative to standard psychological interventions.ConclusionsAdapting scientific evidence into practical guidance for non-specialised health workers in humanitarian settings was challenging due to the paucity of relevant evidence as well as the imprecision and inconsistency of results between studies. Pragmatic outcome evaluation studies from low-resource contexts are urgently needed. Nonetheless, the UNHCR clinical guidance is based on best available evidence and can help to address the compelling issue of undertreated, non-affective psychosis in humanitarian settings.

The Fiscal Sustainability of Alberta's Public Health Care System

From 1975 to 2007, Alberta’s real per capita government health expenditures grew from $1,679 to $3,696 (in 2007 dollars), at a median annual growth rate of 3.5%. Over the same period, Alberta’s real per capita gross domestic product and real per capita total government revenues grew at median annual rates of 2.2% and 1.7%, respectively. This difference between the growth rates of health care spending on the one hand and government revenues and the economy on the other gives rise to concern about the fiscal sustainability of the province’s public health care system. This study presents projections of real per capita spending on public health care in Alberta over the medium term out to 2030. They suggest that, by then, real per capita spending could reach anywhere between $5,339 and $14,215, soaking up between 32% and 87% of total government revenues; more worrying, the high end of these ranges reflects a continuation of the policy settings that guide current provincial public health spending. Alberta is fortunate to have a wealthy economy that can support a high level of public health spending. But that support is precarious given the cyclical nature of non-renewable natural resource revenues and Alberta’s past tendency to experience periods of boom and bust. Basing the financing of key spending programs such as health care on a volatile revenue base is not advisable, for it puts them at risk should economic conditions turn unfavourable, as they have recently. Indeed, adjusting government revenues in our projections to match a more reasonable measure of what might be relied upon with a degree of certainty simply enhances the precariousness of the fiscal sustainability of the public health care system. Not all categories of provincial government health care spending — in particular, the traditional core medicare areas of physician services and hospitals — are growing faster than either the revenue base or the economy. The growth of spending on non-medicare categories such as drugs, capital, and all other health expenditures, however, is a particular source of concern. Options for sustaining provincial government health expenditures include choosing what other government programs could be allowed to grow more slowly over time, what tax rates could be increased to cause the revenue base to grow more quickly, and what health programs currently provided by the public sector instead could be provided privately. These approaches need not exist in watertight compartments, however, and a portfolio of policies that combines these solutions likely would be a pragmatic policy outcome. Such a strategy would help to ensure the fiscal sustainability of Alberta’s public health care system and responsibly provide for the future welfare of its citizens.

Validation of days at home as an outcome measure after surgery: a prospective cohort study in Australia

ObjectiveTo evaluate ‘days at home up to 30 days after surgery’ (DAH30) as a patient-centred outcome measure.DesignProspective cohort study.Data sourceUsing clinical trial data (seven trials, 2109 patients) we calculated DAH30...

Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes.

It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria 5years after a diagnosis of screen-detected diabetes within the ADDITION-Europe study, a pragmatic cardiovascular outcome trial of multifactorial cardiovascular risk management. In 1826 participants with newly diagnosed, screen-detected diabetes without albuminuria, we explored associations between risk of new albuminuria (≥2.5mgmmol-1 for males and ≥3.5mgmmol-1 for females) and (1) baseline cardio-metabolic risk factors and (2) changes from baseline to 1year in systolic blood pressure (ΔSBP) and glycated haemoglobin (ΔHbA1c ) using logistic regression. Albuminuria developed in 268 (15%) participants; baseline body mass index and active smoking were independently associated with new onset albuminuria in 5years after detection of diabetes. In a model adjusted for age, gender, baseline HbA1c and blood pressure, a 1% decrease in HbA1c and 5-mmHg decrease in SBP during the first year were independently associated with lower risks of albuminuria (odds ratio), 95% confidence interval: 0.76, 0.62 to 0.91 and 0.94, 0.88 to 1.01, respectively. Further adjustment did not materially change these estimates. There was no interaction between ΔSBP and ΔHbA1c in relation to albuminuria risk, suggesting likely additive effects on renal microvascular disease. Baseline measurements and changes in HbA1c and SBP a year after diagnosis of diabetes through screening independently associate with new onset albuminuria 4years later. Established multifactorial treatment for diabetes applies to cases identified through screening.

Validation of clinic weights from electronic health records against standardized weight measurements in weight loss trials.

To validate clinic weights in electronic health records against researcher-measured weights for outcome assessment in weight loss trials. Clinic and researcher-measured weights from a published trial (BE WELL) were compared using Lin's concordance correlation coefficient, Bland and Altman's limits of agreement, and polynomial regression model. Changes in clinic and researcher-measured weights in BE WELL and another trial, E-LITE, were analyzed using growth curve modeling. Among BE WELL (n = 330) and E-LITE (n = 241) participants, 96% and 90% had clinic weights (mean [SD] of 5.8 [6.1] and 3.7 [3.9] records) over 12 and 15 months of follow-up, respectively. The concordance correlation coefficient was 0.99, and limits of agreement plots showed no pattern between or within treatment groups, suggesting overall good agreement between researcher-measured and nearest-in-time clinic weights up to 3 months. The 95% confidence intervals for predicted percent differences fell within ±3% for clinic weights within 3 months of the researcher-measured weights. Furthermore, the growth curve slopes for clinic and researcher-measured weights by treatment group did not differ significantly, suggesting similar inferences about treatment effects over time, in both trials. Compared with researcher-measured weights, close-in-time clinic weights showed high agreement and inference validity. Clinic weights could be a valid pragmatic outcome measure in weight loss studies.

Assessing Cognitive Estimation and Its Effects on Community Integration in People with Acquired Brain Injury Undergoing Rehabilitation.

The purpose of the present study was to examine the convergent and divergent validity of the Biber Cognitive Estimation Test (BCET) in individuals with ABI undergoing postacute rehabilitation and to assess the measure's ability to account for unique variance in community integration following rehabilitation. Participants with ABI referred for postacute rehabilitation (N = 201) were assessed on the BCET and a number of other neuropsychological tests that have been demonstrated to rely on aspects of executive processing (Trail-Making Test, Modified Six Elements Test, and verbal fluency measures) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Internal consistency of the total BCET was good; however, interpretable solutions for existing subscales were not discerned. The BCET total score demonstrated positive associations with tests of executive functioning; however, it was also significantly associated with more general aspects of neuropsychological functioning suggesting that it does not solely assess executive processes in ABI patients undergoing rehabilitation. Hierarchical multiple regression suggested that the BCET accounted for significant additional variance in community integration after severity of disability, executive functioning, and more general aspects of neuropsychological status were statistically controlled. While the subscale structure of the BCET may be somewhat inconsistent, the total scale score accounts for some unique variance in pragmatic rehabilitation outcome and may be a useful tool in postacute rehabilitation assessment protocols.

Management of knowledge-intensive organisations: what do we know after 20 years of research?

During the past 20 years a vast amount of academic work has been done in the area of managing knowledge-intensive organisations. Due to the large volume and dispersed nature of prior research it is difficult to gain a holistic view on what is actually known about this issue. This study synthesises the discussion on the management of knowledge-intensive organisations. A literature review was conducted to cover two research questions: first, what are the key characteristics of knowledge-intensive organisations and knowledge work, and second, what are the main managerial issues that originate from the nature of knowledge-intensive organisations? The review makes a contribution by forming a comprehensive view of the key issues involved in managing knowledge-intensive organisations. As its pragmatic outcome the paper provides a managerial checklist that helps to recognise some of the key aspects that are relevant in managing knowledge-intensive organisations.

Management of knowledge-intensive organisations: what do we know after 20 years of research?

During the past 20 years a vast amount of academic work has been done in the area of managing knowledge-intensive organisations. Due to the large volume and dispersed nature of prior research it is difficult to gain a holistic view on what is actually known about this issue. This study synthesises the discussion on the management of knowledge-intensive organisations. A literature review was conducted to cover two research questions: first, what are the key characteristics of knowledge-intensive organisations and knowledge work, and second, what are the main managerial issues that originate from the nature of knowledge-intensive organisations? The review makes a contribution by forming a comprehensive view of the key issues involved in managing knowledge-intensive organisations. As its pragmatic outcome the paper provides a managerial checklist that helps to recognise some of the key aspects that are relevant in managing knowledge-intensive organisations.

Antidepressants and benzodiazepines for panic disorder in adults.

A panic attack is a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. Panic disorder is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, antidepressants and benzodiazepines are the mainstay of treatment for panic disorder. Different classes of antidepressants have been compared; and the British Association for Psychopharmacology, and National Institute for Health and Care Excellence (NICE) consider antidepressants (mainly selective serotonin reuptake inhibitors (SSRIs)) as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In addition to antidepressants, benzodiazepines are widely prescribed for the treatment of panic disorder. To assess the evidence for the effects of antidepressants and benzodiazepines for panic disorder in adults. The Specialised Register of the Cochrane Common Mental Disorders Group (CCMDCTR) to 11 September 2015. This register includes relevant randomised controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-) and PsycINFO (1967-). Reference lists of relevant papers and previous systematic reviews were handsearched. We contacted experts in this field for supplemental data. All double-blind randomised controlled trials allocating adult patients with panic disorder to antidepressants or benzodiazepines versus any other active treatment with antidepressants or benzodiazepines. Two review authors independently checked eligibility and extracted data using a standard form. Data were entered in RevMan 5.3 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings and outcome measures in terms of efficacy, acceptability and tolerability. Thirty-five studies, including 6785 participants overall (of which 5365 in the arms of interest (antidepressant and benzodiazepines as monotherapy)) were included in this review; however, since studies addressed many different comparisons, only a few trials provided data for primary outcomes. We found low-quality evidence suggesting no difference between antidepressants and benzodiazepines in terms of response rate (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.67 to 1.47; participants = 215; studies = 2). Very low-quality evidence suggested a benefit for benzodiazepines compared to antidepressants in terms of dropouts due to any cause, even if confidence interval (CI) ranges from almost no difference to benefit with benzodiazepines (RR 1.64, 95% CI 1.03 to 2.63; participants = 1449; studies = 7). We found some evidence suggesting that serotonin reuptake inhibitors (SSRIs) are better tolerated than TCAs (when looking at the number of patients experiencing adverse effects). We failed to find clinically significant differences between individual benzodiazepines. The majority of studies did not report details on random sequence generation and allocation concealment; similarly, no details were provided about strategies to ensure blinding. The study protocol was not available for almost all studies so it is difficult to make a judgment on the possibility of outcome reporting bias. Information on adverse effects was very limited. The identified studies are not sufficient to comprehensively address the objectives of the present review. The majority of studies enrolled a small number of participants and did not provide data for all the outcomes specified in the protocol. For these reasons most of the analyses were underpowered and this limits the overall completeness of evidence. In general, based on the results of the current review, the possible role of antidepressants and benzodiazepines should be assessed by the clinician on an individual basis. The choice of which antidepressant and/or benzodiazepine is prescribed can not be made on the basis of this review only, and should be based on evidence of antidepressants and benzodiazepines efficacy and tolerability, including data from placebo-controlled studies, as a whole. Data on long-term tolerability issues associated with antidepressants and benzodiazepines exposure should also be carefully considered.The present review highlights the need for further higher-quality studies comparing antidepressants with benzodiazepines, which should be conducted with high-methodological standards and including pragmatic outcome measures to provide clinicians with useful and practical data. Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.

Development Financial Institutions: Impact Investing Practices in Scandinavian Context

Socially responsible Investing (Impact Investing, Sustainable, Ethical, Green investing) that offers pragmatic and social outcome deliveries have become rapidly adopted financial innovations in Scandinavian countries. Impact investing is considered to be one form of socially a responsible investment strategy in the global arena which considers both financial return and social impact (best intentions, outcomes). This research will evaluate Social Impact Investing (SII) practices with particular attention to the private equity companies NORFUND, which is owned by the Norwegian Ministry of Foreign Affairs. Each of three independent case studies is examined in a comparative analysis based on the following criteria: 1) Economic conditions, 2) investment environment, 3) ease of doing business, 4) performance of the Norwegian Development Cooperation, 5) relevance, 6) constraints and 7) opportunities. Results of the analysis show that success or failure of a given venture is tightly coupled to the political environment and existing infrastructure, both financial and real (roads, power distribution etc…). Suggested improvements based on the analysis include a focus on improving several existing programs.