Do coxibs reduce prescription of gastroprotective agents? Results of a record linkage study

BACKGROUND: Coxibs are claimed to be cost-effective drugs and reduced prescription of gastroprotective agents is assumed to be one of their major benefits. Real life prescription of these drugs may be substantially different than that considered in pharmacoeconomic analyses or claimed by drug companies, yet. Our objective was to evaluate whether coxibs were associated with reduced prescription of gastro-protective agents (GPAs, specifically proton pump inhibitors, H(2 )blockers and misoprostol) compared to non selective NSAIDs. METHODS: A record-linkage study was performed using 2001 outpatient prescription data from the province of Modena (about 632,000 inhabitants, in Northern Italy). Logistic regression was used to calculate the odds ratio of GPA prescription for coxib and non-selective NSAID adult users (> 14 years). Three categories of users were further investigated: "acute", "chronic and "incident or new". Main outcome measures were same-day co-prescription and 30 days prescription of GPAs in coxibs and non selective NSAIDs users. To limit selection bias, data were adjusted for age, sex, DDD of coxibs and non selective NSAIDs received during 2001, DDD of GPAs and (for non-incident users) DDD of NSAIDs received during the previous 4 years RESULTS: Same day co-prescription rates were similar considering the overall population and "acute" users. Chronic coxibs users instead showed higher co-prescription rates than chronic NSAIDs users (OR = 1.2, p < 0.05). GPA prescription within thirty days was also higher among all subgroups of coxibs users (OR ranging from 1.6 to 2.0, p < 0.001). CONCLUSION: Assumptions made in pharmacoeconomic analyses on coxibs (lower GPA prescription associated with coxibs use) may be overly optimistic. Claims made through cost-effectiveness data should be carefully interpreted, and mechanisms for attributing drug prices revised accordingly

Clinical Evidence: a useful tool for promoting evidence-based practice?

BACKGROUND: Research has shown that many healthcare professionals have problems with guidelines as they would prefer to be given all relevent information relevent to decision-making rather than being told what they should do. This study assesses doctors' judgement of the validity, relevance, clarity and usability of the Italian translation of Clinical Evidence (CE) after its free distribution launched by the Italian Ministry of Health METHODS: Opinions elicited using a standardised questionnaire delivered either by mail or during educational or professional meetings RESULTS: Twenty percent (n = 1350) doctors participated the study. Most of them found CE's content valid, useful and relevant for their clinical practice, and said CE can foster communications among clinicians, particularly among GPs and specialists. Hospital doctors (63%) more often than GPs (48%) read the detailed presentation of individual chapters. Twenty-nine percent said CE brought changes in their clinical practice. Doctors appreciated CE's nature of an evidence-based information compendium and would have not preferred a collection of practice guidelines. CONCLUSIONS: Overall, the pilot initiative launched by the Italian Ministry of Health seems to have been well received and to support the subsequent decision to make the Italian edition of Clinical Evidence concise available to all doctors practising in the country. Local implementation initiatives should be warranted to favour doctor's use of CE

Short-term and long-term effects of tibolone in postmenopausal women

Background: Tibolone is a synthetic steroid used for the treatment of menopausal symptoms, on the basis of short-term data suggesting its efficacy. We considered the balance between the benefits and risks of tibolone. Objectives: To evaluate the effectiveness and safety of tibolone for treatment of postmenopausal and perimenopausal women. Search methods: In October 2015, we searched the Gynaecology and Fertility Group (CGF) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO (from inception), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and clinicaltrials.gov. We checked the reference lists in articles retrieved. Selection criteria: We included randomised controlled trials (RCTs) comparing tibolone versus placebo, oestrogens and/or combined hormone therapy (HT) in postmenopausal and perimenopausal women. Data collection and analysis: We used standard methodological procedures of The Cochrane Collaboration. Primary outcomes were vasomotor symptoms, unscheduled vaginal bleeding and long-term adverse events. We evaluated safety outcomes and bleeding in studies including women either with or without menopausal symptoms. Main results: We included 46 RCTs (19,976 women). Most RCTs evaluated tibolone for treating menopausal vasomotor symptoms. Some had other objectives, such as assessment of bleeding patterns, endometrial safety, bone health, sexuality and safety in women with a history of breast cancer. Two included women with uterine leiomyoma or lupus erythematosus. Tibolone versus placebo Vasomotor symptoms Tibolone was more effective than placebo (standard mean difference (SMD) -0.99, 95% confidence interval (CI) -1.10 to -0.89; seven RCTs; 1657 women; moderate-quality evidence), but removing trials at high risk of attrition bias attenuated this effect (SMD -0.61, 95% CI -0.73 to -0.49; odds ratio (OR) 0.33, 85% CI 0.27 to 0.41). This suggests that if 67% of women taking placebo experience vasomotor symptoms, between 35% and 45% of women taking tibolone will do so. Unscheduled bleeding Tibolone was associated with greater likelihood of bleeding (OR 2.79, 95% CI 2.10 to 3.70; nine RCTs; 7814 women; I2 = 43%; moderate-quality evidence). This suggests that if 18% of women taking placebo experience unscheduled bleeding, between 31% and 44% of women taking tibolone will do so. Long-term adverse events Most of the studies reporting these outcomes provided follow-up of two to three years (range three months to three years). Breast cancer We found no evidence of differences between groups among women with no history of breast cancer (OR 0.52, 95% CI 0.21 to 1.25; four RCTs; 5500 women; I2= 17%; very low-quality evidence). Among women with a history of breast cancer, tibolone was associated with increased risk (OR 1.5, 95% CI 1.21 to 1.85; two RCTs; 3165 women; moderate-quality evidence). Cerebrovascular events We found no conclusive evidence of differences between groups in cerebrovascular events (OR 1.74, 95% CI 0.99 to 3.04; four RCTs; 7930 women; I2 = 0%; very low-quality evidence). We obtained most data from a single RCT (n = 4506) of osteoporotic women aged 60 to 85 years, which was stopped prematurely for increased risk of stroke. Other outcomes Evidence on other outcomes was of low or very low quality, with no clear evidence of any differences between the groups. Effect estimates were as follows: \u2022 Endometrial cancer: OR 2.04, 95% CI 0.79 to 5.24; nine RCTs; 8504 women; I2 = 0%. \u2022 Cardiovascular events: OR 1.38, 95% CI 0.84 to 2.27; four RCTs; 8401 women; I2 = 0%. \u2022 Venous thromboembolic events: OR 0.85, 95% CI 0.37 to 1.97; 9176 women; I2 = 0%. \u2022 Mortality from any cause: OR 1.06, 95% CI 0.79 to 1.41; four RCTs; 8242 women; I2 = 0%. Tibolone versus combined HT Vasomotor symptoms Combined HT was more effective than tibolone (SMD 0.17, 95% CI 0.06 to 0.28; OR 1.36, 95% CI 1.11 to 1.66; nine studies; 1336 women; moderate-quality evidence). This result was robust to a sensitivity analysis that excluded trials with high risk of attrition bias, suggesting a slightly greater disadvantage of tibolone (SMD 0.25, 95% CI 0.09 to 0.41; OR 1.57, 95% CI 1.18 to 2.10). This suggests that if 7% of women taking combined HT experience vasomotor symptoms, between 8% and 14% of women taking tibolone will do so. Unscheduled bleeding Tibolone was associated with a lower rate of bleeding (OR 0.32, 95% CI 0.24 to 0.41; 16 RCTs; 6438 women; I2 = 72%; moderate-quality evidence). This suggests that if 47% of women taking combined HT experience unscheduled bleeding, between 18% and 27% of women taking tibolone will do so. Long-term adverse events Most studies reporting these outcomes provided follow-up of two to three years (range three months to three years). Evidence was of very low quality, with no clear evidence of any differences between the groups. Effect estimates were as follows: \u2022 Endometrial cancer: OR 1.47, 95% CI 0.23 to 9.33; five RCTs; 3689 women; I2 = 0%. \u2022 Breast cancer: OR 1.69, 95% CI 0.78 to 3.67; five RCTs; 4835 women; I2 = 0%. \u2022 Venous thromboembolic events: OR 0.44, 95% CI 0.09 to 2.14; four RCTs; 4529 women; I2 = 0%. \u2022 Cardiovascular events: OR 0.63, 95% CI 0.24 to 1.66; two RCTs; 3794 women; I2 = 0%. \u2022 Cerebrovascular events: OR 0.76, 95% CI 0.16 to 3.66; four RCTs; 4562 women; I2 = 0%. \u2022 Mortality from any cause: only one event reported (two RCTs; 970 women). Authors' conclusions: Moderate-quality evidence suggests that tibolone is more effective than placebo but less effective than HT in reducing menopausal vasomotor symptoms, and that tibolone is associated with a higher rate of unscheduled bleeding than placebo but with a lower rate than HT. Compared with placebo, tibolone increases recurrent breast cancer rates in women with a history of breast cancer, and may increase stroke rates in women over 60 years of age. No evidence indicates that tibolone increases the risk of other long-term adverse events, or that it differs from HT with respect to long-term safety. Much of the evidence was of low or very low quality. Limitations included high risk of bias and imprecision. Most studies were financed by drug manufacturers or failed to disclose their funding source

Randomised controlled trials for evaluating the prescribing impact of information meetings led by pharmacists and of new information formats, in General Practice in Italy

<p>Abstract</p> <p>Background</p> <p>Suboptimal translation of valid and relevant information in clinical practice is a problem for all health systems. Lack of information independent from commercial influences, limited efforts to actively implement evidence-based information and its limited comprehensibility are important determinants of this gap and may influence an excessive variability in physicians' prescriptions. This is quite noticeable in Italy, where the philosophy and methods of Evidence-Based Medicine still enjoy limited diffusion among practitioners. Academic detailing and pharmacist outreach visits are interventions of proven efficacy to make independent and evidence-based information available to physicians; this approach and its feasibility have not yet been tested on a large scale and, moreover, they have never been formally tested in Italy.</p> <p>Methods/Design</p> <p>Two RCTs are planned:</p> <p>1) a two-arm cluster RCT, carried out in Emilia-Romagna and Friuli Venezia Giulia, will evaluate the effectiveness of small group meetings, randomising about 150 Primary Care Groups (corresponding to about 2000 GPs) to pharmacist outreach visits on two different topics. Physicians' prescriptions (expressed as DDD per 1000 inhabitants/day), knowledge and attitudes (evaluated through the answers to a specific questionnaire) will be compared for target drugs in the two groups (receiving/not receiving each topic).</p> <p>2) A three-arm RCT, carried out in Sardinia, will evaluate both the effectiveness of one-to-one meetings (one pharmacist visiting one physician per time) and of a 'new' information format (compared to information already available) on changing physicians' prescription of specific drugs. About 900 single GPs will be randomised into three groups: physicians receiving a visit supported by "traditional" information material, those receiving a visit with "new" information material on the same topic and those not receiving any visit/material.</p> <p>Discussion</p> <p>The two proposed RCTs aim to evaluate the organisational feasibility and barriers to the implementation of independent information programs led by NHS pharmacists. The objective to assess a 10 or 15% decreases in the prescription of the targeted drugs is quite ambitious in such 'natural' settings, which will be minimally altered by the interventions themselves; this in spite of the quite large sample sizes used comparing to other studies of these kind. Complex interventions like these are not easy to evaluate, given the many different variables into play. Anyway, the pragmatic nature of the two RCTs appears to be also one of their major strengths, helping to provide a deeper insight on what is possible to achieve – in terms of independent information – in a National Health System, with special reference to Italy.</p> <p>Trial registration</p> <p>ISRCTN05866587 (cluster RCT) and ISRCTN28525676 (single GPs RCT)</p

The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/ 27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality

Measuring researchers’ success more fairly: going beyond the H-index

Citation impact indicators play a relevant role in the evaluation of researchers’ scientific production and can influence research funding and future research outputs. The H-index is widely used in this regard, in spite of several shortcomings such as not considering the actual contribution of each author, the number of authors, their overall scientific production and the scientific quality of citing articles. Several authors have highlighted some of these limits. Alternative systems have been proposed but have gained less fortune. In order to show that fairer criteria to assess researchers’ scientific impact can be achieved, a workable example is presented through a novel method, integrating the aforementioned elements by using information available in bibliographic databases. A better, merit-based proxy measure is warranted and can be achieved, although a perfect score without shortcomings is a chimera. Any proposal on a new measure would require clear reasoning, easy math and a consensus between publishers, considering researchers’ and research funders’ point of view. In any case, the relevance of authors’ scientific achievements cannot be adequately represented by a quantitative index only, and qualitative judgements are also necessary. But the time is ripe to make decisions on a fairer, although proxy, measure of scientific outputs

Social marketing: Should it be used to promote evidence-based health information?

The implementation of public health knowledge is a complex process; researchers focus on organizational barriers but generally give little attention to the format and validity of relevant information. Primary and secondary papers and practice guidelines should represent valid and relevant sources of knowledge for clinicians and others involved in public health. However, this information is usually targeted at researchers rather than practitioners; it is often not completely intelligible, does not explain what it really adds to existing knowledge or which clinical/organizational context to place it in, and often lacks 'appeal' for those who are less informed. Moreover, this information is sometimes founded on biased research, shaped by sponsors to give scientific plausibility to market-driven messages. A "social marketing" approach can help public health researchers make evidence-based information clear and appealing. The validity and relevance of this information can be explained to target readers in light of their own knowledge levels and in terms of how this information could help their practice. In this paper we analyse the barriers to knowledge transfer that are often inherent in the format of the information, and propose a more user-friendly, enriched and non-research-article format.Independent drug information Knowledge translation Evidence-based medicine Social marketing Critical appraisal