Citizens' views on prices of medicines reimbursed by the National Health Service: Findings from Italian online focus groups.

INTRODUCTION: Access to medicines is one of the biggest challenges to health systems, affecting society and individuals. This study aims to explore citizens' opinions, perceptions and attitudes on the model of medicines' research and development (R&D) and price setting of medicines reimbursed by the Italian National Health Service. MATERIALS AND METHODS: We run four online focus groups, analysed through thematic analysis. INCLUSION CRITERIA: people aged 30-70 years, who had completed at least compulsory schooling (8-10 years), with no specialised knowledge about the subject. EXCLUSION CRITERIA: healthcare workers, pharmaceutical and device industry employees, researchers and medicine policy board members. We aimed to include a purposive sample of 20 participants, variable in terms of age, educational level and place of residence. RESULTS: Eleven women and six men participated. The mean age was 53 years (range: 28-73). Most (n = 15) had a university degree or attended secondary schools. Eight had a job, five were not employed, and four were retired. In general, participants supported the role of the public health service. Almost all had limited knowledge of medicines' R&D and price setting. Most asked for transparency on medicine prices and negotiation criteria. Participants considered revenues of pharmaceutical companies disproportionate and most called for containment measures of profits. Most were in favour of a stronger public intervention in R&D and prices' negotiations. Few were sceptical of the public sector's ability to play this role. DISCUSSION: Medicines' prices were discussed as a health matter. Increasing citizens' awareness of these topics is needed by providing spaces and conditions to participate in the discussion, including different perspectives and interests. PATIENT OR PUBLIC CONTRIBUTION: Members of BEUC-the European consumer organisation-proposed the project. Altroconsumo, an independent consumer organisation and OCU, a Spanish consumer organisation, participated in developing the project and the main topics to discuss. The Mario Negri Institute and Aplica cooperative-the Spanish methodological team-were involved by BEUC and their national organisations to define the methodology, organisational aspects and contents and conducted the focus groups.

Pharmacological pain and sedation interventions for the prevention of intraventricular hemorrhage in preterm infants on assisted ventilation - an overview of systematic reviews.

BACKGROUND: Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) may contribute to neonatal morbidity and mortality and result in long-term neurodevelopmental sequelae. Appropriate pain and sedation management in ventilated preterm infants may decrease the risk of GMH-IVH; however, it might be associated with harms. OBJECTIVES: To summarize the evidence from systematic reviews regarding the effects and safety of pharmacological interventions related to pain and sedation management in order to prevent GMH-IVH in ventilated preterm infants. METHODS: We searched the Cochrane Library August 2022 for reviews on pharmacological interventions for pain and sedation management to prevent GMH-IVH in ventilated preterm infants (< 37 weeks' gestation). We included Cochrane Reviews assessing the following interventions administered within the first week of life: benzodiazepines, paracetamol, opioids, ibuprofen, anesthetics, barbiturates, and antiadrenergics. Primary outcomes were any GMH-IVH (aGMH-IVH), severe IVH (sIVH), all-cause neonatal death (ACND), and major neurodevelopmental disability (MND). We assessed the methodological quality of included reviews using the AMSTAR-2 tool. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included seven Cochrane Reviews and one Cochrane Review protocol. The reviews on clonidine and paracetamol did not include randomized controlled trials (RCTs) matching our inclusion criteria. We included 40 RCTs (3791 infants) from reviews on paracetamol for patent ductus arteriosus (3), midazolam (3), phenobarbital (9), opioids (20), and ibuprofen (5). The quality of the included reviews was high. The certainty of the evidence was moderate to very low, because of serious imprecision and study limitations. Germinal matrix hemorrhage-intraventricular hemorrhage (any grade) Compared to placebo or no intervention, the evidence is very uncertain about the effects of paracetamol on aGMH-IVH (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.38 to 2.07; 2 RCTs, 82 infants; very low-certainty evidence); midazolam may result in little to no difference in the incidence of aGMH-IVH (RR 1.68, 95% CI 0.87 to 3.24; 3 RCTs, 122 infants; low-certainty evidence); the evidence is very uncertain about the effect of phenobarbital on aGMH-IVH (RR 0.99, 95% CI 0.83 to 1.19; 9 RCTs, 732 infants; very low-certainty evidence); opioids may result in little to no difference in aGMH-IVH (RR 0.85, 95% CI 0.65 to 1.12; 7 RCTs, 469 infants; low-certainty evidence); ibuprofen likely results in little to no difference in aGMH-IVH (RR 0.99, 95% CI 0.81 to 1.21; 4 RCTs, 759 infants; moderate-certainty evidence). Compared to ibuprofen, the evidence is very uncertain about the effects of paracetamol on aGMH-IVH (RR 1.17, 95% CI 0.31 to 4.34; 1 RCT, 30 infants; very low-certainty evidence). Compared to midazolam, morphine may result in a reduction in aGMH-IVH (RR 0.28, 95% CI 0.09 to 0.87; 1 RCT, 46 infants; low-certainty evidence). Compared to diamorphine, the evidence is very uncertain about the effect of morphine on aGMH-IVH (RR 0.65, 95% CI 0.40 to 1.07; 1 RCT, 88 infants; very low-certainty evidence). Severe intraventricular hemorrhage (grade 3 to 4) Compared to placebo or no intervention, the evidence is very uncertain about the effect of paracetamol on sIVH (RR 1.80, 95% CI 0.43 to 7.49; 2 RCTs, 82 infants; very low-certainty evidence) and of phenobarbital (grade 3 to 4) (RR 0.91, 95% CI 0.66 to 1.25; 9 RCTs, 732 infants; very low-certainty evidence); opioids may result in little to no difference in sIVH (grade 3 to 4) (RR 0.98, 95% CI 0.71 to 1.34; 6 RCTs, 1299 infants; low-certainty evidence); ibuprofen may result in little to no difference in sIVH (grade 3 to 4) (RR 0.82, 95% CI 0.54 to 1.26; 4 RCTs, 747 infants; low-certainty evidence). No studies on midazolam reported this outcome. Compared to ibuprofen, the evidence is very uncertain about the effects of paracetamol on sIVH (RR 2.65, 95% CI 0.12 to 60.21; 1 RCT, 30 infants; very low-certainty evidence). Compared to midazolam, the evidence is very uncertain about the effect of morphine on sIVH (grade 3 to 4) (RR 0.08, 95% CI 0.00 to 1.43; 1 RCT, 46 infants; very low-certainty evidence). Compared to fentanyl, the evidence is very uncertain about the effect of morphine on sIVH (grade 3 to 4) (RR 0.59, 95% CI 0.18 to 1.95; 1 RCT, 163 infants; very low-certainty evidence). All-cause neonatal death Compared to placebo or no intervention, the evidence is very uncertain about the effect of phenobarbital on ACND (RR 0.94, 95% CI 0.51 to 1.72; 3 RCTs, 203 infants; very low-certainty evidence); opioids likely result in little to no difference in ACND (RR 1.12, 95% CI 0.80 to 1.55; 5 RCTs, 1189 infants; moderate-certainty evidence); the evidence is very uncertain about the effect of ibuprofen on ACND (RR 1.00, 95% CI 0.38 to 2.64; 2 RCTs, 112 infants; very low-certainty evidence). Compared to midazolam, the evidence is very uncertain about the effect of morphine on ACND (RR 0.31, 95% CI 0.01 to 7.16; 1 RCT, 46 infants; very low-certainty evidence). Compared to diamorphine, the evidence is very uncertain about the effect of morphine on ACND (RR 1.17, 95% CI 0.43 to 3.19; 1 RCT, 88 infants; very low-certainty evidence). Major neurodevelopmental disability Compared to placebo, the evidence is very uncertain about the effect of opioids on MND at 18 to 24 months (RR 2.00, 95% CI 0.39 to 10.29; 1 RCT, 78 infants; very low-certainty evidence) and at five to six years (RR 1.6, 95% CI 0.56 to 4.56; 1 RCT, 95 infants; very low-certainty evidence). No studies on other drugs reported this outcome. AUTHORS' CONCLUSIONS: None of the reported studies had an impact on aGMH-IVH, sIVH, ACND, or MND. The certainty of the evidence ranged from moderate to very low. Large RCTs of rigorous methodology are needed to achieve an optimal information size to assess the effects of pharmacological interventions for pain and sedation management for the prevention of GMH-IVH and mortality in preterm infants. Studies might compare interventions against either placebo or other drugs. Reporting of the outcome data should include the assessment of GMH-IVH and long-term neurodevelopment.

Effectiveness of preconceptional and prenatal cystic fibrosis carrier screening: a systematic review

BACKGROUND: genetic testing for cystic fibrosis (CF) has been offered to people with higher risk of being carrier. OBJECTIVES: to assess the effectiveness of population-based CF carrier screening for adults of reproductive age and its optimal organizational features. DESIGN: systematic review. SETTING AND PARTICIPANTS: MedLine, Embase, Cochrane Library, CINAHL and LILACS (1990-2022) were searched to retrieve primary and secondary studies on adults (16 years and older), with no clinical indication or genetic risk, eligible for genetic testing for CF carrier status. MAIN OUTCOMES MEASURES: attitude to screening, uptake of screening offered, informed reproductive choices. RESULTS: a total of 3,326 records were screened and 292 potentially eligible full-text publications assessed. The review included 71 publications, corresponding to 3 reviews, 40 cohort studies (11 comparative, 29 single-arm), and 6 model studies, published between 1992 and 2021 (median 1998). Only one study compared screening or no screening. This study suggested an association between carrier screening and a lower incidence of CF. Comparative studies examined different approaches for invitation and testing, i.e., settings, target population (individuals/couples, prenatal/preconceptional), how invitations are organized (primary care/maternal hospitals), and format and content of the pre-test information. However, no firm conclusions can be drawn on the impact of these features on informed reproductive choices, uptake, and attitude, because of the limitations of the evidence collected. CONCLUSIONS: the broad heterogeneity of the studies, methodological weaknesses, and the limited transferability of the results mean there is still uncertainty about the effectiveness of preconceptional and prenatal CF carrier screening in the general population.

Interventions for the management of transient tachypnoea of the newborn - an overview of systematic reviews.

BACKGROUND: Transient tachypnoea of the newborn (TTN) is characterised by tachypnoea and signs of respiratory distress. It is caused by delayed clearance of lung fluid at birth. TTN typically appears within the first two hours of life in term and late preterm newborns. Although it is usually a self-limited condition, admission to a neonatal unit is frequently required for monitoring, the provision of respiratory support, and drugs administration. These interventions might reduce respiratory distress during TTN and enhance the clearance of lung liquid. The goals are reducing the effort required to breathe, improving respiratory distress, and potentially shortening the duration of tachypnoea. However, these interventions might be associated with harm in the infant. OBJECTIVES: The aim of this overview was to evaluate the benefits and harms of different interventions used in the management of TTN. METHODS: We searched the Cochrane Database of Systematic Reviews on 14 July 2021 for ongoing and published Cochrane Reviews on the management of TTN in term (> 37 weeks' gestation) or late preterm (34 to 36 weeks' gestation) infants. We included all published Cochrane Reviews assessing the following categories of interventions administered within the first 48 hours of life: beta-agonists (e.g. salbutamol and epinephrine), corticosteroids, diuretics, fluid restriction, and non-invasive respiratory support. The reviews compared the above-mentioned interventions to placebo, no treatment, or other interventions for the management of TTN. The primary outcomes of this overview were duration of tachypnoea and the need for mechanical ventilation. Two overview authors independently checked the eligibility of the reviews retrieved by the search and extracted data from the included reviews using a predefined data extraction form. Any disagreements were resolved by discussion with a third overview author. Two overview authors independently assessed the methodological quality of the included reviews using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) tool. We used the GRADE approach to assess the certainty of evidence for effects of interventions for TTN management. As all of the included reviews reported summary of findings tables, we extracted the information already available and re-graded the certainty of evidence of the two primary outcomes to ensure a homogeneous assessment. We provided a narrative summary of the methods and results of each of the included reviews and summarised this information using tables and figures. MAIN RESULTS: We included six Cochrane Reviews, corresponding to 1134 infants enrolled in 18 trials, on the management of TTN in term and late preterm infants, assessing salbutamol (seven trials), epinephrine (one trial), budesonide (one trial), diuretics (two trials), fluid restriction (four trials), and non-invasive respiratory support (three trials). The quality of the included reviews was high, with all of them fulfilling the critical domains of the AMSTAR 2. The certainty of the evidence was very low for the primary outcomes, due to the imprecision of the estimates (few, small included studies) and unclear or high risk of bias. Salbutamol may reduce the duration of tachypnoea compared to placebo (mean difference (MD) -16.83 hours, 95% confidence interval (CI) -22.42 to -11.23, 2 studies, 120 infants, low certainty evidence). We did not identify any review that compared epinephrine or corticosteroids to placebo and reported on the duration of tachypnoea. However, one review reported on "trend of normalisation of respiratory rate", a similar outcome, and found no differences between epinephrine and placebo (effect size not reported). The evidence is very uncertain regarding the effect of diuretics compared to placebo (MD -1.28 hours, 95% CI -13.0 to 10.45, 2 studies, 100 infants, very low certainty evidence). We did not identify any review that compared fluid restriction to standard fluid rates and reported on the duration of tachypnoea. The evidence is very uncertain regarding the effect of continuous positive airway pressure (CPAP) compared to free-flow oxygen therapy (MD -21.1 hours, 95% CI -22.9 to -19.3, 1 study, 64 infants, very low certainty evidence); the effect of nasal high-frequency (oscillation) ventilation (NHFV) compared to CPAP (MD -4.53 hours, 95% CI -5.64 to -3.42, 1 study, 40 infants, very low certainty evidence); and the effect of nasal intermittent positive pressure ventilation (NIPPV) compared to CPAP on duration of tachypnoea (MD 4.30 hours, 95% CI -19.14 to 27.74, 1 study, 40 infants, very low certainty evidence). Regarding the need for mechanical ventilation, the evidence is very uncertain for the effect of salbutamol compared to placebo (risk ratio (RR) 0.60, 95% CI 0.13 to 2.86, risk difference (RD) 10 fewer, 95% CI 50 fewer to 30 more per 1000, 3 studies, 254 infants, very low certainty evidence); the effect of epinephrine compared to placebo (RR 0.67, 95% CI 0.08 to 5.88, RD 70 fewer, 95% CI 460 fewer to 320 more per 1000, 1 study, 20 infants, very low certainty evidence); and the effect of corticosteroids compared to placebo (RR 0.52, 95% CI 0.05 to 5.38, RD 40 fewer, 95% CI 170 fewer to 90 more per 1000, 1 study, 49 infants, very low certainty evidence). We did not identify a review that compared diuretics to placebo and reported on the need for mechanical ventilation. The evidence is very uncertain regarding the effect of fluid restriction compared to standard fluid administration (RR 0.73, 95% CI 0.24 to 2.23, RD 20 fewer, 95% CI 70 fewer to 40 more per 1000, 3 studies, 242 infants, very low certainty evidence); the effect of CPAP compared to free-flow oxygen (RR 0.30, 95% CI 0.01 to 6.99, RD 30 fewer, 95% CI 120 fewer to 50 more per 1000, 1 study, 64 infants, very low certainty evidence); the effect of NIPPV compared to CPAP (RR 4.00, 95% CI 0.49 to 32.72, RD 150 more, 95% CI 50 fewer to 350 more per 1000, 1 study, 40 infants, very low certainty evidence); and the effect of NHFV versus CPAP (effect not estimable, 1 study, 40 infants, very low certainty evidence). Regarding our secondary outcomes, duration of hospital stay was the only outcome reported in all of the included reviews. One trial on fluid restriction reported a lower duration of hospitalisation in the restricted-fluids group, but with very low certainty of evidence. The evidence was very uncertain for the effects on secondary outcomes for the other five reviews. Data on potential harms were scarce, as all of the trials were underpowered to detect possible increases in adverse events such as pneumothorax, arrhythmias, and electrolyte imbalances. No adverse effects were reported for salbutamol; however, this medication is known to carry a risk of tachycardia, tremor, and hypokalaemia in other settings. AUTHORS' CONCLUSIONS: This overview summarises the evidence from six Cochrane Reviews of randomised trials regarding the effects of postnatal interventions in the management of TTN. Salbutamol may reduce the duration of tachypnoea slightly. We are uncertain as to whether salbutamol reduces the need for mechanical ventilation. We are uncertain whether epinephrine, corticosteroids, diuretics, fluid restriction, or non-invasive respiratory support reduces the duration of tachypnoea and the need for mechanical ventilation, due to the extremely limited evidence available. Data on harms were lacking.

Antiplatelet drugs for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis.

BACKGROUND: Antiplatelet drugs may prevent recurrent ischemic events after ischemic stroke but their relative effectiveness and harms still need to be clarified. Within this network meta-analysis we aimed to summarize the current evidence for using antiplatelet drugs for secondary stroke prevention. METHODS: We searched MEDLINE, EMBASE and CENTRAL up to September 2020. Randomized controlled trials (RCTs) assessing antiplatelet drugs for secondary stroke prevention were included. We did pairwise meta-analyses and network meta-analyses using random-effects models. Primary outcomes were all strokes (ischemic or hemorrhagic) and all-cause mortality. RESULTS: The review included 57 RCTs, 50 (n = 165,533 participants) provided data for the meta-analyses. Compared to placebo/no treatment, moderate to high-confidence evidence indicated that cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day significantly reduced the risk of all strokes (odds ratios, ORs and absolute risk difference, ARD): cilostazol 0.51 (95 % confidence interval, CI, 0.37 to 0.71; 3.6 % fewer), clopidogrel 0.63 (95 % CI, 0.49 to 0.79; 2.7 % fewer), dipyridamole + aspirin 0.65 (95 % CI, 0.55 to 0.78; 2.5 % fewer), ticagrelor 0.68 (95 % CI, 0.50 to 0.93; 2.3 % fewer), ticlopidine 0.74 (95 % CI 0.59 to 0.93; 1.9 % fewer), aspirin ≤ 150 mg/day 0.79 (95 % CI, 0.66 to 0.95; 1.5 % fewer). Aspirin > 150 mg/day and the combinations clopidogrel/aspirin, ticagrelor/aspirin, also decrease all strokes but increase the risk of hemorrhagic events. Only aspirin > 150 mg/day significantly reduced all-cause mortality (OR 0.86, 95 % CI 0.76 to 0.97; ARD 0.9 %, 95 %CI 1.5-0.2 % fewer, moderate confidence). Compared to aspirin ≤ 150 mg/day, clopidogrel significantly reduced the risk of all strokes, cardiovascular events, and intracranial hemorrhage outcomes. Cilostazol also appeared to provide advantages but data are limited to the Asian population. CONCLUSIONS: Considering the benefits and harms ratio, cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day appear to be the best choices as antiplatelet drugs for secondary prevention of patients with ischemic stroke or TIA. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020159896 .

Food and Drug Administration vs European Medicines Agency: Review times and clinical evidence on novel drugs at the time of approval.

The Food and Drug Administration (FDA) and European Medicines Agency (EMA) now have expedited review procedures for new drugs. We compared the review times of medicines licensed by the 2 agencies and explored differences in the evidence submitted. In 2015-2017 the FDA licensed 113 drugs, 66 of which reached Europe. The median review time was longer at the EMA than FDA and was shorter for drugs undergoing FDA-expedited programmes compared to the same drugs approved by the EMA through the standard procedure. We identified differences regarding the evidence submitted to the 2 regulators for 7 drugs. The greater use of expedited programmes by the FDA and administrative time at the European Commission mainly explain the later access of new drugs to the European market. The additional evidence submitted to the EMA is generally scant and limited to a few drugs.

Clinical evidence supporting the marketing authorization of biosimilars in Europe.

PURPOSE: To review the marketing authorization of biosimilars and provide a critical analysis of the pivotal trials supporting their approval by the European Medicines Agency (EMA). METHODS: EMA website to identify the biosimilars approved up to July 2019 and the European Public Assessment Report for information on pivotal trial design, duration, intervention and control, primary outcome, data on immunogenicity, and comparability margins. RESULTS: The EMA has approved 55 biosimilars (62% in 2017-2019) of 16 biologic products, used in several clinical indications. Some biosimilars were licensed as multiple products, with different commercial names, by the same or different companies. The comparability exercise and subsequent approval of 49/55 (89%) biosimilars were based on one or more pivotal phase III trials testing their clinical efficacy. In all, biosimilars were approved on the basis of 55 trials, mostly phase III (42/55, 76%) assessing clinical efficacy; these were mainly equivalence trials (31/55, 56%). The pivotal phase III trials assessed surrogate measures of clinical effect, and 71% reported immunogenicity data. CONCLUSION: Analysis of the approval of biosimilars in Europe depicts a complex and heterogeneous scenario. The requirement for showing similarity in terms of clinical efficacy and safety provides a robust demonstration of comparable clinical outcomes but lays a burden on biosimilar manufacturers and may delay the introduction of the drugs. The development, licensing, and monitoring of biosimilars would benefit from new strategies to accelerate access to these drugs while reducing uncertainties about their use in practice.

Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis.

BACKGROUND: Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary prevention for patients with ischemic stroke by comparing benefits and harms of various statins. METHODS: We searched for randomized controlled trials (RCTs) assessing statins in patients with ischemic stroke or transient ischemic attack (TIA) in MEDLINE, EMBASE, and CENTRAL up to July 2017. Two authors extracted data and appraised risks of bias. We performed pairwise meta-analyses and trial sequential analyses (TSA) to compare statins versus placebo/no statin, and network meta-analyses using frequentist random-effects models to compare statins through indirect evidence. We used GRADE to rate the overall certainty of evidence. Primary outcomes were all-cause mortality and all strokes. Secondary outcomes were different types of strokes, cardiovascular events, and adverse events. RESULTS: We identified nine trials (10,741 patients). No head-to-head RCTs were found. The median follow-up period was 2.5 years. Statins did not seem to modify all stroke and all-cause mortality outcomes; they were associated with a decreased risk of ischemic stroke (odds ratio, OR, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, ARD, - 1.6% [95% CI, - 2.6 to - 0.6%]), ischemic stroke or TIA (OR, 0.75 [95% CI, 0.64 to 0.87]; ARD, - 4.2% [95% CI, - 6.2 to - 2.1%]), and cardiovascular event (OR, 0.75 [95% CI, 0.69 to 0.83]; ARD, - 5.4% [95% CI, - 6.8 to - 3.6%]), and did not seem to modify rhabdomyolysis, myalgia, or rise in creatine kinase. In the comparison of different statins, moderate- to high-quality evidence indicated that differences between pharmaceutical products seemed modest, with high doses (e.g., atorvastatin 80 mg/day and simvastatin 40 mg/day) associated with the greatest benefits. TSA excluded random error as a cause of the findings for ischemic stroke and cardiovascular event outcomes. Evidence for increased risk of hemorrhagic stroke was sensitive to the exclusion of the SPARCL trial. CONCLUSIONS: Evidence strongly suggests that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events. Differences in effects among statins were modest, signaling potential therapeutic equivalence. TRIAL REGISTRATION: PROSPERO CRD42018079112.

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.

BACKGROUND: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. METHODS AND FINDINGS: NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and <27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease-specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, -0.07-1.64) at 13 weeks, 6.41 (5.33-7.49) at 52 weeks, and 9.63 (8.33-10.93) at 78 weeks and on nilvadipine was 0.88 (0.02-1.74) at 13 weeks, 5.75 (4.66-6.85) at 52 weeks, and 9.41 (8.09-10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. CONCLUSIONS: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.

E-learning for health professionals.

BACKGROUND: The use of e-learning, defined as any educational intervention mediated electronically via the Internet, has steadily increased among health professionals worldwide. Several studies have attempted to measure the effects of e-learning in medical practice, which has often been associated with large positive effects when compared to no intervention and with small positive effects when compared with traditional learning (without access to e-learning). However, results are not conclusive. OBJECTIVES: To assess the effects of e-learning programmes versus traditional learning in licensed health professionals for improving patient outcomes or health professionals' behaviours, skills and knowledge. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and three trial registers up to July 2016, without any restrictions based on language or status of publication. We examined the reference lists of the included studies and other relevant reviews. If necessary, we contacted the study authors to collect additional information on studies. SELECTION CRITERIA: Randomised trials assessing the effectiveness of e-learning versus traditional learning for health professionals. We excluded non-randomised trials and trials involving undergraduate health professionals. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed risk of bias. We graded the certainty of evidence for each outcome using the GRADE approach and standardised the outcome effects using relative risks (risk ratio (RR) or odds ratio (OR)) or standardised mean difference (SMD) when possible. MAIN RESULTS: We included 16 randomised trials involving 5679 licensed health professionals (4759 mixed health professionals, 587 nurses, 300 doctors and 33 childcare health consultants).When compared with traditional learning at 12-month follow-up, low-certainty evidence suggests that e-learning may make little or no difference for the following patient outcomes: the proportion of patients with low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL (adjusted difference 4.0%, 95% confidence interval (CI) -0.3 to 7.9, N = 6399 patients, 1 study) and the proportion with glycated haemoglobin level of less than 8% (adjusted difference 4.6%, 95% CI -1.5 to 9.8, 3114 patients, 1 study). At 3- to 12-month follow-up, low-certainty evidence indicates that e-learning may make little or no difference on the following behaviours in health professionals: screening for dyslipidaemia (OR 0.90, 95% CI 0.77 to 1.06, 6027 patients, 2 studies) and treatment for dyslipidaemia (OR 1.15, 95% CI 0.89 to 1.48, 5491 patients, 2 studies). It is uncertain whether e-learning improves or reduces health professionals' skills (2912 health professionals; 6 studies; very low-certainty evidence), and it may make little or no difference in health professionals' knowledge (3236 participants; 11 studies; low-certainty evidence).Due to the paucity of studies and data, we were unable to explore differences in effects across different subgroups. Owing to poor reporting, we were unable to collect sufficient information to complete a meaningful 'Risk of bias' assessment for most of the quality criteria. We evaluated the risk of bias as unclear for most studies, but we classified the largest trial as being at low risk of bias. Missing data represented a potential source of bias in several studies. AUTHORS' CONCLUSIONS: When compared to traditional learning, e-learning may make little or no difference in patient outcomes or health professionals' behaviours, skills or knowledge. Even if e-learning could be more successful than traditional learning in particular medical education settings, general claims of it as inherently more effective than traditional learning may be misleading.

Heparin for the prevention of intraventricular haemorrhage in preterm infants.

BACKGROUND: Preterm birth remains the major risk factor for the development of intraventricular haemorrhage, an injury that occurs in 25% of very low birth weight infants. Intraventricular haemorrhage is thought to be venous in origin and intrinsic thromboses in the germinal matrix are likely to play a triggering role. Heparin activates antithrombin and promotes the inactivation of thrombin and other target proteinases. The administration of anticoagulants such as heparin may offset the increased risk of developing intraventricular haemorrhage and may also reduce the risk of developing parenchymal venous infarct, a condition known to complicate intraventricular haemorrhage. OBJECTIVES: To assess whether the prophylactic administration of heparin reduces the incidence of germinal matrix-intraventricular haemorrhage in very preterm neonates when compared to placebo, no treatment, or other anticoagulants. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2015), MEDLINE (1996 to 22 November 2015), EMBASE (1980 to 22 November 2015) and CINAHL (1982 to 22 November 2015), applying no language restrictions. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia and New Zealand and Pediatric Academic Societies) from 2000 to 2015. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing the administration of early, i.e. within the first 24 hours of life, heparin in very preterm infants (gestational age < 32 weeks). DATA COLLECTION AND ANALYSIS: For each of the included trials, two authors independently extracted data (e.g. number of participants, birth weight, gestational age, dose of heparin, mode of administration, and duration of therapy, etc.) and assessed the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow up). The primary outcomes considered in this review are intraventricular haemorrhage, severe intraventricular haemorrhage and neonatal mortality. MAIN RESULTS: Two randomised controlled trials enrolling a total of 155 infants met the inclusion criteria of this review. Both trials compared low-dose heparin to the same solution without heparin in very preterm newborns requiring umbilical catheterisation. No trials were identified that specifically studied the use of heparin in infants at risk of germinal matrix-intraventricular haemorrhage.We found no differences in the rates of intraventricular haemorrhage (typical RR 0.93, 95% CI 0.61 to 1.41; typical RD -0.03, 95% CI -0.17 to 0.12; 2 studies, 155 infants; I² = 57% for RR and I² = 65% for RD), severe intraventricular haemorrhage (typical RR 1.01, 95% CI 0.46 to 2.23; typical RD 0.00, 95% CI -0.11 to 0.11; 2 studies, 155 infants; I² = 0% for RR and I² = 0% for RD) and neonatal mortality (typical RR 0.69, 95% CI 0.28 to 1.67; typical RD -0.04, 95% CI -0.14 to 0.06; 2 studies, 155 infants; I² = 28% for RR and I² = 50% for RD). We judged the quality of the evidence supporting these findings as very low (rates of intraventricular haemorrhage) and low (severe intraventricular haemorrhage and neonatal mortality) mainly because of limitations in the study designs and the imprecision of estimates. We found very few data on other relevant outcomes, such as bronchopulmonary dysplasia, pulmonary haemorrhage and patent ductus arteriosus; and no study assessing long-term outcomes (e.g. neurodevelopmental disability). AUTHORS' CONCLUSIONS: There is very limited data on the effect of prophylactic administration of heparin on the incidence and severity of IVH in very preterm neonates. Both the identified trials used heparin in the context of maintaining umbilical line patency and not specifically as an agent to prevent germinal matrix-intraventricular haemorrhage. Given the imprecision of our estimates, the results of this systematic review are consistent with either a benefit or a detrimental effect of heparin and do not provide a definitive answer to the review question. Limited evidence is available on other clinically relevant outcomes.

Antithrombin for the prevention of intraventricular hemorrhage in very preterm infants.

BACKGROUND: Preterm birth remains the major risk factor for the development of intraventricular hemorrhage, an injury that occurs in 25% of very low birth weight infants. Intraventricular hemorrhage is thought to be venous in origin and intrinsic thromboses in the germinal matrix are likely to play a triggering role. Antithrombin, a glycoprotein synthesized in the liver, is the major plasma inhibitor of thrombin thus modulating blood coagulation. Very low birth weight newborn infants have low levels of antithrombin and the risk of developing intraventricular hemorrhage is increased by the presence of hypercoagulability in the first hours of life. The administration of anticoagulants such as antithrombin may offset the increased risk of developing intraventricular hemorrhage. Anticoagulants may also reduce the risk of developing parenchymal venous infarct, a condition known to complicate intraventricular hemorrhage. OBJECTIVES: To assess whether the prophylactic administration of antithrombin (started within the first 24 hours after birth) reduces the incidence of germinal matrix-intraventricular hemorrhage in very preterm neonates when compared to placebo, no treatment, or heparin. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2015), MEDLINE (1996 to 22 November 2015), EMBASE (1980 to 22 November 2015), and CINAHL (1982 to 22 November 2015). No language restrictions were applied. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia and New Zealand and Pediatric Academic Societies) from 2000 to 2015. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing the administration of early, i.e. within the first 24 hours of life, antithrombin in very preterm infants (gestational age < 32 weeks, any birth weight). DATA COLLECTION AND ANALYSIS: For each of the included trials, two authors independently extracted data (e.g. number of participants, birth weight, gestational age, antithrombin formulation (plasma-derived or recombinant), mode of administration, and duration of therapy, etc.) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review are intraventricular hemorrhage and severe intraventricular hemorrhage. MAIN RESULTS: Two randomized controlled trials, for a total of 182 infants, met the inclusion criteria of this review. Both trials compared antithrombin with placebo. We found no significant differences in the rates of intraventricular hemorrhage (typical RR 1.30, CI 95% 0.87 to 1.93, typical RD 0.09, 95% CI -0.05 to 0.23; 2 studies, 175 infants; I² = 18% for RR and I² = 42% for RD) and severe intraventricular hemorrhage (typical RR 1.04, CI 95% 0.55 to 1.94; typical RD 0.01, 95% CI -0.11 to 0.12; 2 studies, 175 infants; I² = 0% for RR and I² = 0% for RD). Among secondary outcomes, we found no significant differences in terms of neonatal mortality (typical RR 2.00, CI 95% 0.62 to 6.45; typical RD 0.04, 95% CI -0.03 to 0.12; 2 studies, 182 infants; I² = 46% for RR and I² = 61% for RD) and in the other specified outcomes, such as bronchopulmonary dysplasia. The quality of the evidence supporting these findings is limited due to the imprecision of the estimates. AUTHORS' CONCLUSIONS: The administration of antithrombin seems not to reduce the incidence and severity of intraventricular hemorrhage in very preterm infants. Limited evidence is available on other clinically relevant outcomes. Given the imprecision of the estimate, the results of this systematic review are consistent with either a benefit or a detrimental effect of antithrombin and do not provide a definitive answer to the review question.

Providing Doctors With High-Quality Information: An Updated Evaluation of Web-Based Point-of-Care Information Summaries.

BACKGROUND: The complexity of modern practice requires health professionals to be active information-seekers. OBJECTIVE: Our aim was to review the quality and progress of point-of-care information summaries-Web-based medical compendia that are specifically designed to deliver pre-digested, rapidly accessible, comprehensive, and periodically updated information to health care providers. We aimed to evaluate product claims of being evidence-based. METHODS: We updated our previous evaluations by searching Medline, Google, librarian association websites, and conference proceedings from August 2012 to December 2014. We included Web-based, regularly updated point-of-care information summaries with claims of being evidence-based. We extracted data on the general characteristics and content presentation of products, and we quantitatively assessed their breadth of disease coverage, editorial quality, and evidence-based methodology. We assessed potential relationships between these dimensions and compared them with our 2008 assessment. RESULTS: We screened 58 products; 26 met our inclusion criteria. Nearly a quarter (6/26, 23%) were newly identified in 2014. We accessed and analyzed 23 products for content presentation and quantitative dimensions. Most summaries were developed by major publishers in the United States and the United Kingdom; no products derived from low- and middle-income countries. The main target audience remained physicians, although nurses and physiotherapists were increasingly represented. Best Practice, Dynamed, and UptoDate scored the highest across all dimensions. The majority of products did not excel across all dimensions: we found only a moderate positive correlation between editorial quality and evidence-based methodology (r=.41, P=.0496). However, all dimensions improved from 2008: editorial quality (P=.01), evidence-based methodology (P=.015), and volume of diseases and medical conditions (P<.001). CONCLUSIONS: Medical and scientific publishers are investing substantial resources towards the development and maintenance of point-of-care summaries. The number of these products has increased since 2008 along with their quality. Best Practice, Dynamed, and UptoDate scored the highest across all dimensions, while others that were marketed as evidence-based were less reliable. Individuals and institutions should regularly assess the value of point-of-care summaries as their quality changes rapidly over time.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of migraine in adults.

BACKGROUND: This is an updated version of the original Cochrane review published in 2005 on selective serotonin reuptake inhibitors (SSRIs) for preventing migraine and tension-type headache. The original review has been split in two parts and this review now only regards migraine prevention. Another updated review is under development to cover tension-type headache.Migraine is a common disorder. The chronic forms are associated with disability and have a high economic impact. In view of discoveries about the role of serotonin and other neurotransmitters in pain mechanisms, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been evaluated for the prevention of migraine. OBJECTIVES: To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic migraine in adults. SEARCH METHODS: For the original review, we searched MEDLINE (1966 to January 2004), EMBASE (1994 to May 2003), the Cochrane Central Register of Controlled Trials (CENTRAL 2003, Issue 4), and Headache Quarterly (1990 to 2003). For this update, we applied a revised search strategy to reflect the broader type of intervention (SSRIs and SNRIs). We searched CENTRAL (2014, Issue 10), MEDLINE (1946 to November 2014), EMBASE (1980 to November 2014), and PsycINFO (1987 to November 2014). We also checked the reference lists of retrieved articles and searched trial registries for ongoing trials. SELECTION CRITERIA: We included randomised controlled trials comparing SSRIs or SNRIs with any type of control intervention in participants 18 years and older of either sex with migraine. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data (migraine frequency, index, intensity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the risk of bias of trials. The primary outcome of this updated review is migraine frequency. MAIN RESULTS: The original review included eight studies on migraine. Overall, we now include 11 studies on five SSRIs and one SNRI with a total of 585 participants. Six studies were placebo-controlled, four compared a SSRI or SNRI to amitriptyline, and one was a head-to-head comparison (escitalopram versus venlafaxine). Most studies had methodological or reporting shortcomings (or both): all studies were at unclear risk of selection and reporting bias. Follow-up rarely extended beyond three months. The lack of adequate power of most of the studies is also a major concern.Few studies explored the effect of SSRIs or SNRIs on migraine frequency, the primary endpoint. Two studies with unclear reporting compared SSRIs and SNRIs to placebo, suggesting a lack of evidence for a difference. Two studies compared SSRIs or SNRIs versus amitriptyline and found no evidence for a difference in terms of migraine frequency (standardised mean difference (SMD) 0.04, 95% confidence interval (CI) -0.72 to 0.80; I(2) = 72%), or other secondary outcomes such as migraine intensity and duration.SSRIs or SNRIs were generally more tolerable than tricyclics. However, the two groups did not differ in terms of the number of participants who withdrew due to adverse advents or for other reasons (one study, odds ratio (OR) 0.39, 95% CI 0.10 to 1.50 and OR 0.42, 95% CI 0.13 to 1.34).We did not find studies comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. antiepileptics and anti-hypertensives). AUTHORS' CONCLUSIONS: Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine as preventive drugs for migraine. There is no evidence to consider SSRIs or venlafaxine as more effective than placebo or amitriptyline in reducing migraine frequency, intensity, and duration over two to three months of treatment. No reliable information is available at longer-term follow-up. Our conclusion is that the use of SSRIs and SNRIs for migraine prophylaxis is not supported by evidence.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension-type headache in adults.

BACKGROUND: This is an updated version of the Cochrane review published in 2005 on selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headache. The original review has been split in two parts and this review now only regards tension-type headache prevention. Another updated review covers migraine. Tension-type headache is the second most common disorder worldwide and has high social and economic relevance. As serotonin and other neurotransmitters may have a role in pain mechanisms, SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been evaluated for the prevention of tension-type headache. OBJECTIVES: To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic tension-type headache in adults. SEARCH METHODS: For the original review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2003, Issue 4), MEDLINE (1966 to January 2004), EMBASE (1994 to May 2003), and Headache Quarterly (1990 to 2003). For this update, we revised the original search strategy to reflect the broader type of intervention (SSRIs and SNRIs). We searched CENTRAL (2014, Issue 10) on the Cochrane Library, MEDLINE (1946 to November 2014), EMBASE (1980 to November 2014), and PsycINFO (1987 to November 2014). We also checked the reference lists of retrieved articles and searched trial registries for ongoing trials. SELECTION CRITERIA: We included randomised controlled trials comparing SSRIs or SNRIs with any type of control intervention in participants 18 years and older, of either sex, with tension-type headache. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data (headache frequency, index, intensity, and duration; use of symptomatic/analgesic medication; quality of life; and withdrawals) and assessed the risk of bias of trials. The primary outcome is tension-type headache frequency, measured by the number of headache attacks or the number of days with headache per evaluation period. MAIN RESULTS: The original review included six studies on tension-type headache. We now include eight studies with a total of 412 participants with chronic forms of tension-type headache. These studies evaluated five SSRIs (citalopram, sertraline, fluoxetine, paroxetine, fluvoxamine) and one SNRI (venlafaxine). The two new studies included in this update are placebo controlled trials, one evaluated sertraline and one venlafaxine. Six studies, already included in the previous version of this review, compared SSRIs to other antidepressants (amitriptyline, desipramine, sulpiride, mianserin). Most of the included studies had methodological and/or reporting shortcomings and lacked adequate power. Follow-up ranged between two and four months.Six studies explored the effect of SSRIs or SNRIs on tension-type headache frequency, the primary endpoint. At eight weeks of follow-up, we found no difference when compared to placebo (two studies, N = 127; mean difference (MD) -0.96, 95% confidence interval (CI) -3.95 to 2.03; I(2)= 0%) or amitriptyline (two studies, N = 152; MD 0.76, 95% CI -2.05 to 3.57; I(2)= 44%).When considering secondary outcomes, SSRIs reduce the symptomatic/analgesic medication use for acute headache attacks compared to placebo (two studies, N = 118; MD -1.87, 95% CI -2.09 to -1.65; I(2)= 0%). However, amitriptyline appeared to reduce the intake of analgesic more efficiently than SSRIs (MD 4.98, 95% CI 1.12 to 8.84; I(2)= 0%). The studies supporting these findings were considered at unclear risk of bias. We found no differences compared to placebo or other antidepressants in headache duration and intensity.SSRIs or SNRI were generally more tolerable than tricyclics. However, the two groups did not differ in terms of number of participants who withdrew due to adverse events or for other reasons (four studies, N = 257; odds ratio (OR) 1.04; 95% CI 0.41 to 2.60; I(2)= 25% and OR 1.55, 95% CI 0.71 to 3.38; I(2)= 0%).We did not find any study comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. botulinum toxin) or non-drug therapies (e.g. psycho-behavioural treatments, manual therapy, acupuncture). AUTHORS' CONCLUSIONS: Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine (a SNRI) as preventive drugs for tension-type headache. Over two months of treatment, SSRIs or venlafaxine are no more effective than placebo or amitriptyline in reducing headache frequency in patients with chronic tension-type headache. SSRIs seem to be less effective than tricyclic antidepressants in terms of intake of analgesic medications. Tricyclic antidepressants are associated with more adverse events; however, this did not cause a greater number of withdrawals. No reliable information is available at longer follow-up. Our conclusion is that the use of SSRIs and venlafaxine for the prevention of chronic tension-type headache is not supported by evidence.

[Barriers and facilitators to the implementation of computerized decision support systems in Italian hospitals: a grounded theory study]. / Barriere e facilitatori all'implementazione dei sistemi di supporto decisionale computerizzati in ospedale: uno studio "grounded theory".

INTRODUCTION: Computerized Decision Support Systems (CDSSs) connect health care professionals with high-quality, evidence-based information at the point-of-care to guide clinical decision-making. Current research shows the potential of CDSSs to improve the efficiency and quality of patient care. The mere provision of the technology, however, does not guarantee its uptake. This qualitative study aims to explore the barriers and facilitators to the use of CDSSs as identified by health providers. METHODS: The study was performed in three Italian hospitals, each characterized by a different level of familiarity with the CDSS technology. We interviewed frontline physicians, nurses, information technology staff, and members of the hospital board of directors (n=24). A grounded theory approach informed our sampling criteria as well as the data collection and analysis. RESULTS: The adoption of CDSSs by health care professionals can be represented as a process that consists of six "positionings," each corresponding to an individual's use and perceived mastery of the technology. In conditions of low mastery, the CDSS is perceived as an object of threat, an unfamiliar tool that is difficult to control. On the other hand, individuals in conditions of high mastery view the CDSS as a helpful tool that can be locally adapted and integrated with clinicians' competences to fulfil their needs. In the first positionings, the uptake of CDSSs is hindered by representational obstacles. The last positionings, alternatively, featured technical obstacles to CDSS uptake. DISCUSSION: Our model of CDSS adoption can guide hospital administrators interested in the future integration of CDSSs to evaluate their organizational contexts, identify potential challenges to the implementation of the technology, and develop an effective strategy to address them. Our findings also allow reflections concerning the misalignment between most Italian hospitals and the current innovation trends toward the uptake of computerized decision support technologies.

Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis.

BACKGROUND: Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. METHODS: We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. FINDINGS: We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69-82) of CIN2 or worse and 84% (72-92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83-89) and 87% (84-90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0·88 [95% CI 0·85-0·91] for CIN2 or worse and 0·89 [0·83-0·96] for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0·96 [0·95-0·97] for CIN2 or worse and 0·96 [0·93-0·99] for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. INTERPRETATION: In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. FUNDING: The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology.

[Cystic fibrosis carrier screening: a Health technology assessment.] / Lo screening del portatore di fibrosi cistica: una valutazione di Health technology assessment.

This project of Health technology assessment was aimed at defining the impacts of offering a cystic fibrosis (CF) carrier screening to the general population, compared to the current situation, where the test is offered to individuals at high-risk to give birth to a child with CF. Results revealed: i) a lack of robust and updated data; ii) a return on investment up to six years from the screening's introduction, despite important economic and organizational efforts; iii) a general positive attitude of healthcare professionals, people with CF, families and general population; iv) possible issues related to the social impact.

User-experience testing of an evidence-to-decision framework for selecting essential medicines.

Essential medicine lists (EMLs) are important medicine prioritization tools used by the World Health Organization (WHO) EML and over 130 countries. The criteria used by WHO's Expert Committee on the Selection and Use of Essential Medicines has parallels to the GRADE Evidence-to-Decision (EtD) frameworks. In this study, we explored the EtD frameworks and a visual abstract as adjunctive tools to strengthen the integrate evidence and improve the transparency of decisions of EML applications. We conducted user-experience testing interviews of key EML stakeholders using Morville's honeycomb model. Interviews explored multifaceted dimensions (e.g., usability) on two EML applications for the 2021 WHO EML-long-acting insulin analogues for diabetes and immune checkpoint inhibitors for lung cancer. Using a pre-determined coding framework and thematic analysis we iteratively improved both the EtD framework and the visual abstract. We coded the transcripts of 17 interviews with 13 respondents in 103 locations of the interview texts across all dimensions of the user-experience honeycomb. Respondents felt the EtD framework and visual abstract presented complementary useful and findable adjuncts to the traditional EML application. They felt this would increase transparency and efficiency in evidence assessed by EML committees. As EtD frameworks are also used in health practice guidelines, including those by the WHO, respondents articulated that the adoption of the EtD by EML applications represents a tangible mechanism to align EMLs and guidelines, decrease duplication of work and improve coordination. Improvements were made to clarify instructions for the EtD and visual abstract, and to refine the design and content included. 'Availability' was added as an additional criterion for EML applications to highlight this criterion in alignment with WHO EML criteria. EtD frameworks and visual abstracts present additional important tools to communicate evidence and support decision-criteria in EML applications, which have global health impact. Access to essential medicines is important for achieving universal health coverage, and the development of essential medicine lists should be as evidence-based and trustworthy as possible.