Measuring the value of solidarity: The abem financial assistance program for out-of-pocket payments on pharmacy medicines in Portugal.

OBJECTIVE: Out-of-pocket payments for prescribed medicines are still comparatively high in Portugal. The abem program was launched in Portugal in May 2016 to aid vulnerable groups by completely covering out-of-pocket costs of prescribed medicines in community pharmacies. This study assesses the impact of the program on poverty and catastrophic health expenditures. METHODS: A longitudinal study was carried out with the analysis of several program databases (from the beginning of the program in May 2016 to September 2018) covering the cohorts of beneficiaries, daily data on medicines dispensed, social referencing entities, and solidarity pharmacies. The study provides estimates of standard poverty measures (intensity and severity) as well as the incidence of catastrophic health expenditures. RESULTS: More than 6000 beneficiaries were supported (56.8% female, 34.7% aged 65 or over), encompassing 127,510 medicines (mainly nervous system and cardiovascular system) with an average 26.9% co-payment (payments totalling €1.5 million). The program achieved substantial reductions in poverty (3.4% in intensity, 5.6% in severity), and eliminated cases with catastrophic health expenditures in medicines that would have affected 7.5% of the beneficiaries. CONCLUSIONS: Findings confirm a continuous increase in the number of beneficiaries, enabling access to medicines especially for the vulnerable elderly, and a sizable impact on eliminating out-of-pocket payments for medicines in the target population.

General health check-ups: To check or not to check? A question of choosing wisely.

In high-income countries, regular general health check-ups are part of the fabric of the health care systems. The hidden concept of general health check-ups, promoted for more than a century, is to identify diseases at a stage at which early intervention can be effective. However, there has been little evidence to support the benefits of such checkups. Choosing wisely (CW) campaigns may represent a tremendous opportunity to eventually shift patients and physicians away from the non-evidence based yet firmly entrenched practice of the general health check-up. As campaign leaders and members of the CW working group of the European Federation of Internal Medicine, we want to join the discussion by giving our perspective based on the best available evidence.

Histology-Agnostic Drugs: A Paradigm Shift-A Narrative Review.

Cancer diagnosis and therapeutics have been traditionally based on pathologic classification at the organ of origin. The availability of an unprecedented amount of clinical and biologic data provides a unique window of opportunity for the development of new drugs. What was once treated as a homogeneous disease with a one-size-fits-all approach was shown to be a rather heterogeneous condition, with multiple targetable mutations that can vary during the course of the disease. Clinical trial designs have had to adapt to the exponential growth of targetable mechanisms and new agents, with ensuing challenges that are closer to those experienced with rare diseases and orphan medicines. To face these problems, precision/enrichment and other novel trial designs have been developed, and the concept of histology-agnostic targeted therapeutic agents has emerged. Patients are selected for a specific agent based on specific genomic or molecular alterations, with the same compound used to potentially treat a multiplicity of cancers, granted that the actionable driver alteration is present. There are currently approved drugs for such indications, but this approach has raised issues on multiple levels. This review aims to address the challenges of this new concept and provide insights into possible solutions and frameworks on how to tackle them.

Pharmacy interventions on COVID-19 in Europe: Mapping current practices and a scoping review.

BACKGROUND: The COVID-19 pandemic has put community pharmacists at the frontline of prevention, preparedness, response, and recovery efforts. Pharmacies had to reorganize and implement several different interventions and measures within a very short time frame. OBJECTIVES: 1) To map the current reported practice and trends and to review the literature on pharmacy-based interventions on COVID-19 provided in Europe; 2) To identify knowledge gaps and future avenues for pharmacy research, policy, and practice in response to public health emergencies. METHODS: We used a mixed methods approach combining country mapping of current practices of pharmacy interventions on COVID-19 reported by pharmacy associations in Europe with a scoping review of published literature. RESULTS: We mapped current practices on 31 pharmacy interventions on COVID-19 in 32 countries in Europe. Almost all preventive measures to reduce health risks have been provided in most countries. Other frequent interventions reflected preparedness for stockpiling, increased demand for services and products, and important patient care interventions exceeding dispensing role. Expanded powers granted to pharmacies and legislation passed in view of COVID-19 enabled services that improve access to medicines and relevant products, patient screening and referral including point-of-care antigen testing, support to vulnerable patients, and COVID-19 vaccination. We identified 9 studies conducted in pharmacies in 7 countries in Europe. Most studies are cross-sectional and/or descriptive. Pharmacy associations played an important supporting role by developing and updating guidance and emergency plans to assist community pharmacists. CONCLUSIONS: A wide array of pharmacy interventions on COVID-19 was implemented in several countries within a very short time frame. Research on pharmacy interventions on COVID-19 is still in its infancy but confirmed the wide array of interventions provided and expanded powers granted to pharmacies. These findings may provide a significant impact to improve pharmacy research, policy, and practice in response to future public health emergencies in Europe and globally.

Reply to Comment on Nogueira, P.J., et al. "The Role of Health Preconditions on COVID-19 Deaths in Portugal: Evidence from Surveillance Data of the First 20293 Infection Cases". J. Clin. Med. 2020, 9, 2368.

We thank Costa-Santos C [...].

Costs and consequences of the Portuguese needle-exchange program in community pharmacies.

BACKGROUND: Needle-exchange programs (NEPs) reduce infections in people who inject drugs. This study assesses the impact community pharmacies have had in the Needle-Exchange Program in Portugal since 2015. METHODS: Health gains were measured by the number of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections averted, which were estimated, in each scenario, based on a standard model in the literature, calibrated to national data. The costs per infection were taken from national literature; costs of manufacturing, logistics and incineration of injection materials were also considered. The results were presented as net costs (i.e., incremental costs of the program with community pharmacies less the costs of additional infections avoided). RESULTS: Considering a 5-year horizon, the Needle Exchange Program with community pharmacies would account for a 6.8% (n = 25) and a 6.5% reduction (n = 22) of HCV and HIV infections, respectively. The present value of net savings generated by the participation of community pharmacies in the program was estimated at €2,073,347. The average discounted net benefit per syringe exchanged is €3.01, already taking into account a payment to community pharmacies per needle exchanged. INTERPRETATION: We estimate that the participation of community pharmacies in the Needle Exchange Program will lead to a reduction of HIV and HCV infections and will generate over €2 million in savings for the health system. CONCLUSIONS: The intervention is estimated to generate better health outcomes at lower costs, contributing to improving the efficiency of the public health system in Portugal.

Effectiveness of needle and syringe Programmes in people who inject drugs - An overview of systematic reviews.

BACKGROUND: Needle and syringe programmes (NSP) are a critical component of harm reduction interventions among people who inject drugs (PWID). Our primary objective was to summarize the evidence on the effectiveness of NSP for PWID in reducing blood-borne infection transmission and injecting risk behaviours (IRB). METHODS: We conducted an overview of systematic reviews that included PWID (excluding prisons and consumption rooms), addressed community-based NSP, and provided estimates of the effect regarding incidence/prevalence of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV), Hepatitis B virus (HBV) and bacteremia/sepsis, and/or measures of IRB. Systematic literature searches were undertaken on relevant databases, including EMBASE, MEDLINE, and PsychINFO (up to May 2015). For each review we identified relevant studies and extracted data on methods, and findings, including risk of bias and quality of evidence assessed by review authors. We evaluated the risk of bias of each systematic review using the ROBIS tool. We categorized reviews by reported outcomes and use of meta-analysis; no additional statistical analysis was performed. RESULTS: We included thirteen systematic reviews with 133 relevant unique studies published between 1989 and 2012. Reported outcomes related to HIV (n = 9), HCV (n = 8) and IRB (n = 6). Methods used varied at all levels of design and conduct, with four reviews performing meta-analysis. Only two reviews were considered to have low risk of bias using the ROBIS tool, and most included studies were evaluated as having low methodological quality by review authors. We found that NSP was effective in reducing HIV transmission and IRB among PWID, while there were mixed results regarding a reduction of HCV infection. Full harm reduction interventions provided at structural level and in multi-component programmes, as well as high level of coverage, were more beneficial. CONCLUSIONS: The heterogeneity and the overall low quality of evidence highlights the need for future community-level studies of adequate design to support these results. TRIAL REGISTRATION: The protocol of this systematic review was registered in Prospective Register of Systematic Reviews (PROSPERO 2015: CRD42015026145 ).

Effect of dignity therapy on end-of-life psychological distress in terminally ill Portuguese patients: A randomized controlled trial.

OBJECTIVE: Dignity therapy (DT) is a brief form of psychotherapy developed for patients living with a life-limiting illness that has demonstrated efficacy in treating several dimensions of end-of-life psychological distress. Our aim was to determine the influence of DT on demoralization syndrome (DS), the desire for death (DfD), and a sense of dignity (SoD) in terminally ill inpatients experiencing a high level of distress in a palliative care unit. METHOD: A nonblinded phase II randomized controlled trial was conducted with 80 patients who were randomly assigned to one of two groups: the intervention group (DT + standard palliative care [SPC]) or the control group (SPC alone). The main outcomes were DS, DfD, and SoD, as measured according to DS criteria, the Desire for Death Rating Scale, and the Patient Dignity Inventory (PDI), respectively. All scales were assessed at baseline (day 1) and at day 4 of follow-up. This study is registered with http://www.controlled-trials.com/ISRCTN34354086. RESULTS: Of the 80 participants, 41 were randomized to DT and 39 to SPC. Baseline characteristics were similar between the two groups. DT was associated with a significant decrease in DS compared with SPC (DT DS prevalence = 12.1%; SPC DS prevalence = 60.0%; p < 0.001). Similarly, DT was associated with a significant decrease in DfD prevalence (DT DfD prevalence = 0%; SPC DfD prevalence = 14.3%; p = 0.054). Compared with participants allocated to the control group, those who received DT showed a statistically significant reduction in 19 of 25 PDI items. SIGNIFICANCE OF RESULTS: Dignity therapy had a beneficial effect on the psychological distress encountered by patients near the end of life. Our research suggests that DT is an important psychotherapeutic approach that should be included in clinical care programs, and it could help more patients to cope with their end-of-life experiences.

The place of DPP-4 inhibitors in the treatment algorithm of diabetes type 2: a systematic review of cost-effectiveness studies.

OBJECTIVE: To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics. METHODS: Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list. RESULTS: A total of 295 studies were identified, of which 20 were included. The average quality score was 0.720 on a 0-1 scale. All studies were performed in high- and middle-income countries, using a 3rd-party payer perspective and randomized clinical trials to measure effectiveness. Sitagliptin, saxagliptin and vildagliptin had an ICER below 25,000 €/QALY, as second-line and as add-ons to metformin, in comparison to sulfonylureas. When compared with sitagliptin, liraglutide (GLP-1 receptor agonist) had an ICER of up to 22,724 €/QALY for the 1.2-mg dosage, and up to 32,869 €/QALY for the 1.8-mg dosage. Insulin glargine was dominant when compared with sitagliptin. CONCLUSIONS: According to the WHO threshold applied to the country and year of each study, DPP-4 inhibitors were highly cost-effective as second-line, as add-ons to metformin, in comparison with sulfonylureas. More recent therapies (GLP-1 receptor agonists and insulin glargine) were highly cost-effective in comparison to DPP-4 inhibitors. These results were obtained, however, on the basis of a limited number of studies, relying on the same few clinical trials, and financed by manufacturers. Further independent research is needed to confirm these findings.

[Abstract of Cochrane review]. / Resumo da revisão Cochrane.

Objectivos: Esta revisão sistemática destinou-se a determinar os efeitos sobre a mortalidade e morbilidade do rastreio do cancro da mama com mamografia em mulheres de risco baixo e em cuidados primários.Material e Métodos: Foram pesquisadas duas bases de dados - PubMed (Novembro 2012) e a World Health Organization's International Clinical Trials Registry Platform (Novembro 2012) ­ para identificação de ensaios clínicos aleatorizados, prospectivos e controlados (Randomized Clinical trials ­ RCTs) comparando o rastreio com a não realização do rastreio. A extracção dos dados foi feita por dois investigadores que contactaram, quando necessário, os autores dos estudos para informação adicional.Resultados: Foram identificados 8 RCTs cujas amostras somaram 600 000 mulheres com idades entre 39-74 anos. Os resultados agregados dos ensaios de melhor qualidade metodológica (baixo risco de viés de selecção) não detectaram diferenças na mortalidade por cancro da mama aos 7 (risco relativo [RR] = 0,93; Intervalo de Confiança [IC] 95%: 0,79-1,09) ou aos 13 anos (RR = 0,90; IC 95%: 0,79-1,02). Os resultados agregados dos ensaios com maior risco de viés de selecção (por possível aleatorização inadequada) mostraram reduções significativas na mortalidade por cancro da mama aos 7 (RR = 0,71; IC95%: 0,61-0,83) e aos 13 anos (RR = 0,75; IC95%: 0,67-0,83). Não se verificou heterogeneidade entre os resultados dos estudos. Os resultados dos estudos de melhor epior qualidade metodológica foram semelhantes para as mulheres com menos e com mais de 50 anos de idade. Quer os resultados dos estudos de melhor qualidade, quer os resultados dos estudos com maior risco de viés, não encontraram diferenças na mortalidade oncológica (por todos os tipos de cancro) nem na mortalidade global, quer aos 7, quer aos 13 anos. Devido a deficiente classificação das causas de morte nas amostras dos RCTs, a mortalidade por cancro da mama revelou-se um resultado (outcome) enviesado a favor do rastreio. O número total de lumpectomias e mastectomias foi significativamente superior nos grupos rastreados (RR=1,31,IC95%: 1,22-1,42); no que se refere às mastectomias, os valores foram também mais altos: RR=1,20 (IC95%: 1,08-1,32). Verificou-se ainda uma utilização mais intensiva de radioterapia nos grupos rastreados (dados de 2 RCTs).Conclusões: Estes resultados indicam que não está demonstrado que o rastreio do cancro da mama com mamografia tenha umbenefício-risco favorável em mulheres de baixo risco rastreadas em cuidados primários.

[Off-label prescribing: scientific analysis taking the use of bevacizumab in ophthalmology as an example]. / Prescrição off-label: análise científica tendo como exemplo a utilização de bevacizumab em oftalmologia.

Off-label prescribing poses specific technical/scientific, professional and ethical problems. In this study we carry out a technical and scientific analysis of the off-label prescribing using a current, clinical and economically relevant example: the paradigmatic case of the use of bevacizumab in ophthalmologic pathologies for which it has no formal indication. We conducted a systematic review of the literature on the efficacy and safety of this drug, as well as ranibizumab - which has approved ophthalmologic indications, in order to qualitatively analyze the available evidence on the two interventions. This is a typical case for technical and scientific analysis of the off-label prescribing problems. According to the results of the systematic review, the use of bevacizumab in this context has in fact scientific evidence of appreciable size, including clinical trials head-to-head with ranibizumab. However, the identified safety issues raise the question of the use of this drug in ophthalmologic pathologies. The different players involved in the treatment decisions (physicians, patients and institutional decision makers) should be adequately informed about the existing evidence that supports off-label prescribing which, by definition, must always be on an exceptional basis and properly justified.

A prescrição off-label levanta problemas técnicos/científicos, profissionais e éticos específicos. No presente trabalho, procurámos realizar uma análise técnico-científica da prescrição off-label recorrendo a um exemplo atual, clinica e economicamente relevante: o caso paradigmático da utilização de bevacizumab em patologias do foro oftalmológico para as quais não tem indicação formal aprovada. Para tal realizámos uma revisão sistemática da literatura sobre a eficácia e segurança deste medicamento, assim como de ranibizumab­ o qual tem indicações oftalmológicas aprovadas, no sentido de analisar qualitativamente a evidência científica disponível sobreas duas intervenções. Este caso é exemplar para análise técnico-científica dos problemas da prescrição off-label, já que, de acordo com os resultados da revisão sistemática realizada, o uso do bevacizumab neste contexto possui, de facto, evidência científica de dimensão apreciável, incluindo ensaios clínicos head-to-head com ranibizumab. No entanto, os problemas de segurança identificados levantam a questão da utilização deste fármaco nas patologias oftalmológicas. Os diferentes agentes que participam no processo de decisão terapêutica (médicos, doentes e decisores institucionais) devem estar adequadamente informados sobre a evidência existente que suporta a prescrição off-label, a qual, por definição, deve ser sempre de caracter excecional e devidamente justificada.

[Off-label prescription: practice and problems]. / A prescrição fora das indicações aprovadas (off-label): prática e problemas.

Approval of a drug for clinical use requires production of data on efficacy and safety through submission of results from randomized controlled trials (RCTs), in which the new molecule is usually compared with placebo (or an active comparator) for a set of outcomes that will serve as the basis for the drug's indications. These indications are crucial, because drugs are approved on the basis of their net clinical benefit for specific and well-defined diseases and--importantly--only for these. Once the drug is available for use in tens or hundreds of thousands of patients, physicians may realize that some medications can be effective in diseases for which they were not approved, i.e., no studies have been presented to the regulatory authorities, and therefore they are not formally approved for those indications. Convinced of the benefits for their patients, some physicians prescribe them for unapproved indications--off-label prescription. In this paper we discuss the prevalence of off-label prescription, and its advantages and problems.

Is the OSCE a feasible tool to assess competencies in undergraduate medical education?

BACKGROUND: The Objective Structured Clinical Examination (OSCE) was introduced by Harden et al. (1975) trying to answer the problems regarding the assessment of clinical competencies. Despite increasingly widespread use of OSCEs, debate continues with arguments as 'why using such a demanding format if other methods are available?' AIM: To review and synthesize evidence on technical and economic feasibility of OSCE in undergraduate medical studies. METHODS: Best Evidence Medical Education methodology was applied by two independent coders to 1083 studies identified by literature search from 1975 until the end of 2008. KEY FINDINGS: The OSCE is a feasible approach to the assessment of clinical competence for use in different cultural and geographical contexts; to assess a wide range of learning outcomes; in different specialties and disciplines; for formative and summative purposes; to assess students a curriculum or an educational intervention; in the different phases of education including the early and later years of the undergraduate curriculum; and in different health care professions. CONCLUSION: Despite being an expensive test format, evidence suggests that the use of OSCE produces reliable results. The study also suggests that one reason for the wide-scale adoption of the OSCE and the feasibility of its use in different contexts and situations is its inherent flexibility in terms of the number of students that can be assessed, the number of examiners included, the type of patients represented and the format of the examination itself, including the length of the examination, the number and duration of stations.

Diagnostic characteristics of tests: sensitivity, specificity, predictive values and likelihood ratios.

The diagnostic process always involves two sequential steps: the first assesses the patient's clinical situation through data obtained from the history and physical examination, and the second requests tests to confirm the diagnostic hypothesis. The first step belongs to cognitive psychology and has its own biases and learning methods. The second is based on scientific data that defines the discriminatory power of tests from studies comparing a new test (the so-called index test) and the gold standard for diagnosing the disease. In this article we present a classification of the diagnostic characteristics of tests using a 2x2 contingency table. This information can be used to support the rational use of diagnostic tests.

Bias in clinical studies.

Clinical studies are designed fundamentally to obtain data to support practice, whether diagnostic, therapeutic or prognostic. No matter how well a study was designed, implemented or analyzed, it is never possible to guarantee the truth of its results with absolute certainty. This is due to two factors that can change the study's results: random error and systematic error (also called bias). The first appears without warning and cannot be modulated, while the second--defined as the systematic introduction of error into a study--can be removed (if not completely, at least partially). In this paper we present the most common types of bias found in clinical studies, whether therapeutic (clinical trials), or with other experimental or observational designs.