Dominik Glinz

In Ivorian school-age children, infection with hookworm does not reduce dietary iron absorption or systemic iron utilization, whereas afebrile Plasmodium falciparum infection reduces iron absorption by half

BACKGROUND In sub-Saharan Africa, parasitic diseases and low bioavailable iron intake are major causes of anemia. Anemia results from inflammation, preventing iron recycling and decreasing dietary iron absorption. Hookworm, Plasmodium, and Schistosoma infections contribute to anemia, but their influence on dietary iron absorption and recycling is unknown. OBJECTIVE The objective was to measure inflammation biomarkers, hepcidin, iron absorption, and utilization pre- and posttreatment in children with afebrile malaria, hookworm, and Schistosoma haematobium infection. DESIGN Ivorian children aged 11-17 y with afebrile Plasmodium falciparum (n = 17), hookworm (n = 16), or S. haematobium infection (n = 8) consumed a syrup containing 3 mg ⁵⁷Fe as ferrous sulfate and received an intravenous infusion of 50 μg ⁵⁸Fe as ferrous citrate. Children were treated for their respective infection, and the iron studies were repeated 4 wk later. Iron and inflammation biomarkers and hepcidin were measured. RESULTS Geometric mean iron absorptions in the afebrile malaria and hookworm groups were 12.9% and 32.2% (P < 0.001) before treatment and 23.6% and 30.0% (P = 0.113) after treatment, respectively. Treatment of afebrile malaria reduced inflammation (P < 0.001) and serum hepcidin (P = 0.004) and improved iron absorption (P = 0.003). Treatment of hookworm infection neither affected inflammation biomarkers nor altered iron absorption. Similarly, there was a lack of treatment effects in the S. haematobium-infected group; however, the small sample size limits conclusions. Geometric mean iron utilization ranged between 79.1% and 88.0% in the afebrile malaria and hookworm groups with no significant differences pre- and posttreatment. CONCLUSIONS In school-age children, hookworm infection does not produce inflammation or increase serum hepcidin, and it does not influence iron absorption or utilization. In contrast, afebrile malaria causes inflammation, increases hepcidin, and reduces iron absorption but not utilization. These findings provide insights into the iron metabolism and the etiology of anemia in parasitic infections.

Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis

Colchicine is an old anti-inflammatory drug that has shown substantial cardiovascular benefits in recent trials. We systematically reviewed cardiovascular benefits and harms of colchicine in any population and specifically in patients with high cardiovascular risk. We evaluated randomised controlled trials comparing colchicine over at least 6 months versus any control in any adult population. Primary outcomes were all-cause mortality, myocardial infarction and adverse events. Cardiovascular mortality was a secondary outcome. We included 39 trials with 4992 patients. The quality of evidence for mortality outcomes and myocardial infarction was moderate but lower for adverse events. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; I2=27%; 30 trials). Cardiovascular mortality was reduced in some but not all meta-analytical models (random-effects RR 0.34, 0.09 to 1.21, I2=9%; Petos OR 0.24, 0.09 to 0.64, I2=15%; Mantel-Haenszel fixed-effect RR 0.20, 0.06 to 0.68, I2=0%; 7 trials). The risk for myocardial infarction was reduced (RR 0.20, 0.07 to 0.57; 2 trials). There was no effect on total adverse events (RR 1.52, 0.93 to 2.46, I2=45%; 11 trials) but gastrointestinal intolerance was increased (RR 1.83, 1.03 to 3.26, I2=74%; 11 trials). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects in high cardiovascular risk populations were similar (4 trials; 1230 patients). We found no evidence supporting colchicine doses above 1 mg/day. Colchicine may have substantial cardiovascular benefits; however, there is sufficient uncertainty about its benefit and harm to indicate the need for large-scale trials to further evaluate this inexpensive, promising treatment in cardiovascular disease.

Personalized Prescription Feedback Using Routinely Collected Data to Reduce Antibiotic Use in Primary Care: A Randomized Clinical Trial

Importance Feedback interventions using routinely collected health data might reduce antibiotic use nationwide without requiring the substantial resources and structural efforts of other antibiotic stewardship programs. Objective To determine if quarterly antibiotic prescription feedback over 2 years reduces antibiotic use when implemented in a complex health care system. Design, Setting, and Participants Pragmatic randomized trial using routinely collected claims data on 2900 primary care physicians with the highest antibiotic prescription rates in Switzerland. Interventions Physicians were randomized to quarterly updated personalized antibiotic prescription feedback over 2 years (n = 1450) or usual care (n = 1450). Feedback was provided both by mail and online from October 2013 to October 2015 and was supported by an initial 1-time provision of evidence-based guidelines. Main Outcomes and Measures The primary outcome was the prescribed defined daily doses (DDD) of any antibiotic to any patient per 100 consultations in the first year analyzed by intention-to-treat. We further analyzed prescriptions of specific antibiotics, age groups, and sex for the first and second year to investigate persistency of effects over time. Results The 2900 physicians had 10 660 124 consultations over 2 years of follow-up, prescribed 1 175 780 packages of antibiotics with 10 290 182 DDD. Physicians receiving feedback prescribed the same amount of antibiotics to all patients in the first year (between-group difference, 0.81%; 95% CI, −2.56% to 4.30%; P = .64) and second year (between-group difference, −1.73%; 95% CI, −5.07% to 1.72%; P = .32) compared with the control group. Prescribing to children aged 6 to 18 years was −8.61% lower in the feedback than in the control group in the first year (95% CI, −14.87% to −1.90%; P = .01). This difference diminished in the second year (between-group difference, −4.10%; 95% CI, −10.78% to 3.07%; P = .25). Physicians receiving feedback prescribed fewer antibiotics to adults aged 19 to 65 years in the second year (between-group difference, −4.59%; 95% CI, −7.91% to −1.16%; P < .01). Prescribing to other patient groups or of specific antibiotic types was not significantly different between groups. Conclusions and Relevance This nationwide antibiotic stewardship program with routine feedback on antibiotic prescribing was not associated with a change of antibiotic use. In older children, adolescents, and younger adults less antibiotics were prescribed, but not consistently over the entire intervention period. Trial Registration clinicaltrials.gov Identifier: NCT01773824

Iron Fortified Complementary Foods Containing a Mixture of Sodium Iron EDTA with Either Ferrous Fumarate or Ferric Pyrophosphate Reduce Iron Deficiency Anemia in 12- to 36-Month-Old Children in a Malaria Endemic Setting: A Secondary Analysis of a Cluster-Randomized Controlled Trial

Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a 9-month cluster-randomized controlled trial conducted in south-central Côte d’Ivoire. 378 children aged 12–36 months were randomly assigned to no food intervention (n = 125; control group), CF fortified with 2 mg NaFeEDTA plus 3.8 mg FeFum for six days/week (n = 126; FeFum group), and CF fortified with 2 mg NaFeEDTA and 3.8 mg FePP for six days/week (n = 127; FePP group). The outcome measures were hemoglobin (Hb), plasma ferritin (PF), iron deficiency (ID; PF < 30 μg/L), and anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for inflammation. The prevalence of Plasmodium falciparum infection and inflammation during the study were 44–66%, and 57–76%, respectively. There was a significant time by treatment interaction on IDA (p = 0.028) and a borderline significant time by treatment interaction on ID with or without anemia (p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total anemia. These data indicate that, despite the high endemicity of malaria and elevated inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of NaFeEDTA with FeFum or NaFeEDTA with FePP. However, there was no overall effect on anemia, suggesting most of the anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).

Cost-effectiveness of primarily surgical versus primarily conservative treatment of acute and subacute radiculopathies due to intervertebral disc herniation from the Swiss perspective

AIMS OF THE STUDY To assess the cost-effectiveness of primarily surgical treatment (PST) versus primarily conservative treatment (PCT) in adults with intermediate severity, acute or subacute, lumbar radicular syndrome due to intervertebral disc herniation. METHODS A decision analytic model from healthcare system and societal perspectives was used to compare outcomes and costs of PST with those of PCT (physiotherapy, epidural injection and medication). Treatment pathways and quality of life were obtained from published clinical trials. Costs were derived from Swiss health insurance claims data. Swiss clinical experts provided information on use of medication and physiotherapy. The main outcome of interest was incremental cost per quality-adjusted-life-year (QALY) gained over a period of 2 years. Costs and QALYs gained were discounted from the second year, at a rate of 2% per year. RESULTS In the base-case analysis from a healthcare system perspective, over 2 years, PST compared with PCT led to 0.0634 additional QALYs per person, at an additional net cost of CHF 7198 per person. The corresponding incremental cost effectiveness ratio (ICER) amounted to CHF 113 396 per QALY gained. From a societal perspective the ICER was CHF 70 711 per QALY gained. ICERs were subject to substantial uncertainty because of limitations in available data. CONCLUSION A PST approach, when compared with PCT, may be cost effective from a societal perspective based on a willingness-to-pay threshold of CHF 100 000 per QALY gained. However, it is less likely to be cost effective from the perspective of the Swiss healthcare system. More research is needed to understand the long-term economic implications among this patient group.

Adaptation of cost-effectiveness analyses to a single country: the case of bariatric surgery for obesity and overweight

BACKGROUND AND OBJECTIVES Bariatric surgery is the most effective treatment for morbid obesity and is known to have beneficial effects on glycaemic control in patients with type 2 diabetes mellitus (T2DM) and in diabetes prevention. The preferred type of surgery and mechanism of action is, however, unclear. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effects of laparoscopic roux-en-Y gastric bypass (RYGB) with those of sleeve gastrectomy (SG) on metabolic outcome, with a special focus on glycaemic control. METHODS A literature search of the Medline, Pubmed, Cochrane, Embase and SCOPUS databases was performed in November 2014 for RCTs comparing RYGB with SG in overweight and obese patients with or without T2DM. The primary outcome was improvement in postoperative glycaemic control. Secondary outcomes included weight-related and lipid metabolism parameters. Synthesis of these data followed established statistical procedures for meta-analysis. RESULTS Sixteen RCTs with a total of 1132 patients with overweight or obesity were included in the analysis. When compared with patients who underwent SG, those who underwent RYGB showed no difference after 12 months in mean fasting blood glucose (mean difference [MD] -6.22 mg/dl, 95% confidence interval [CI] -17.27 to 4.83; p <0.001). However, there was a better outcome with RYGB, with lower mean fasting glucose levels at 24 months (MD -16.92 mg/dl, 95% CI -21.67 to -12.18), 36 months (MD -5.97mg/dl, 95% CI -9.32 to -2.62) and at 52 months (MD -15.20 mg/dl, 95% CI -27.35 to -3.05) mg/dl; p = 0.010) and lower mean glycated haemoglobin (HbA1 at 12 months (MD -0.47%, 95% CI -0.73 to -0.20%; p <0.001) and at 36 months postoperatively compared to SG. Fasting insulin levels and HOMA indices showed no difference at any stage of follow-up. In the subgroup including only diabetic patients HbA1c showed lower levels at 12 months (MD -0.46%, 95% CI-0.73 to -0.20%). No difference was found for the fasting insulin at baseline and after 12 months. Similarly, when compared to SG, patients that underwent RYGB had lower low-density lipoproteins at 12 months. This effect was lost at 36 months. Patients undergoing RYGB also had lower triglycerides at 12 months and at 52 months, lower cholesterol at 60 months and an improvement of BMI at 52 months postoperatively. BMI values at 12 months and low-density lipoprotein levels at 12 and 36 months were lower for diabetic patients only, as in the overall analysis. CONCLUSION Based on this meta-analysis, RYGB is more effective than SG in improving weight loss and short- and mid-term glycaemic and lipid metabolism control in patients with and without T2DM. Therefore, unless contraindicated, RYGB should be the first choice to treat patients with obesity and T2DM and/or dyslipidaemia.OBJECTIVES The aims of this study were to (a) identify and assess the quality of reporting of published cost-effectiveness studies of bariatric surgery, (b) assess their transferability to Switzerland, and (c) adapt transferable cost-effectiveness results to Switzerland. METHODS A systematic literature search was performed in Medline, Embase and other databases. Two reviewers independently undertook screening, extraction, assessment of reporting quality utilising the Consolidated Health Economic Evaluation Reporting Standards, transferability, adaptation of cost data and recalculation of cost-effectiveness results. Cost data were adapted in three steps: correction for different levels of resource utilisation, for different prices of healthcare services and for change in costs over time. RESULTS Fifteen studies fulfilled criteria for adaptation of cost data to Switzerland. Four out of fifteen adapted studies with a long time-horizon for patients with a body mass index (BMI) >35kg/m2 indicated bariatric surgery to be a cost-saving (dominant) approach compared with conventional treatment. Other studies for patients with BMI >35kg/m2 showed cost-effective results, with incremental cost-effectiveness ratios (ICERs) below CHF 50,000 per quality adjusted life-year (QALY) gained. Two studies assessed cost-effectiveness for patients with BMI <35kg/m2, and revealed ICERs below 50,000 per QALY gained for bariatric surgery versus conventional treatment. Between-study differences were related to approaches for the modelling effectiveness and costs, time horizon, population, type of intervention and possibly other unidentified reasons. Gastric bypass appeared to be superior to gastric banding, but was more expensive. CONCLUSIONS Nearly all studies found bariatric surgery to be a cost saving or cost-effective compared with conventional treatment. The adaptation of existing cost-effectiveness analyses cannot be considered to give accurate ICERs for Switzerland, but may have achieved an approximation of cost-effectiveness levels to be expected for Switzerland. It has made the results of international cost-effectiveness studies reported for different countries and in different currencies more comparable, and may be useful for individual countries in which financing or capacity for economic analyses is scarce.

Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC4 E): the ALIC4 E protocol

Introduction Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. Methods and analysis Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12–64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48–72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. Ethics and dissemination Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. Trial registration number ISRCTN27908921; Pre-results.