Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice.

BACKGROUND: New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2. METHODS: A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to  adverse events (AEs). The Kaplan-Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used. RESULTS: There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7-35.2) and median duration of treatment was 17.5 months (IQR: 7.8-29.1). Median PFS was 19.5 months (95%CI 14.2-24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2-75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5-50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4-28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4-36.0). TPF was 19.8 months (95%CI 14.2-24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0-29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%). CONCLUSIONS: Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.

Can we use existing guidance to support the development of robust real-world evidence for health technology assessment/payer decision-making?

Advances in the digitization of health systems and expedited regulatory approvals of innovative treatments have led to increased potential for the use of real-world data (RWD) to generate real-world evidence (RWE) to complement evidence from clinical trials. However, health technology assessment (HTA) bodies and payers have concerns about the ability to generate RWE of sufficient quality to be pivotal evidence of relative treatment effectiveness. Consequently, there is a growing need for HTA bodies and payers to develop guidance for the industry and other stakeholders about the use of RWD/RWE to support access, reimbursement, and pricing. We therefore sought to (i) understand barriers to the use of RWD/RWE by HTA bodies and payers; (ii) review potential solutions in the form of published guidance; and (iii) review findings with selected HTA/payer bodies. Four themes considered key to shaping the generation of robust RWE for HTA bodies and payers were identified as: (i) data (availability, governance, and quality); (ii) methodology (design and analytics); (iii) trust (transparency and reproducibility); and (iv) policy and partnerships. A range of guidance documents were found from trusted sources that could address these themes. These were discussed with HTA experts. This commentary summarizes the potential guidance solutions available to help resolve issues faced by HTA decision-makers in the adoption of RWD/RWE. It shows that there is alignment among stakeholders about the areas that need improvement in the development of RWE and that the key priority to move forward is better collaboration to make data usable for multiple purposes.

Implications of a defined daily dose fixed database for drug utilization research studies: The case of statins in Portugal.

AIMS: Given the discrepancies between PDDs (prescribed daily doses) and DDDs (defined daily doses), we aimed to assess the extent of error in the results of an 18-year population-level study on statin utilization in Portugal. METHODS: The Portuguese regulatory agency provided data for the period 2000-2018 on statin dispensing (C10AA). The DDDs were gathered from the ATC/DDD database. DDDs were calculated by the DDD year-by-year approach (DDDYEAR ) and by the DDD last-year approach (DDDLAST ). PDDs were calculated according to the year-by-year approach (PDDYEAR ). Statin annual utilization rates per 1000 inhabitants per day were also calculated. Percent errors were calculated for PDDYEAR and DDDYEAR units. RESULTS: The DDDYEAR approach revealed decreases in the consumption of atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin in 2009, when their DDD was modified. Conversely, the results from both DDDLAST and PDDYEAR approaches indicated gradual changes in the actual consumption of all statins in Portugal. Before 2009, atorvastatin, pravastatin and simvastatin utilization was greatly overestimated by DDDYEAR /1000 inhabitants/day. The average dose of lovastatin prescribed in the past 18 years (20 mg) was below the assigned DDDs during the study period, varying from 30 mg to 45 mg. Conversely, the PDD for fluvastatin was above the DDD values (ranging from 40 mg in 2000 to 70 mg in 2016). For atorvastatin, pravastatin and simvastatin, national PDDs were above the assigned DDD until the DDD modification in 2009. CONCLUSIONS: A more dynamic system, based on national and annually updated DDDs, should be able to reduce discrepancies between DDDs and PDDs and the bias in utilization studies.

Monitoring real-life utilization of pembrolizumab in advanced melanoma using the Portuguese National Cancer Registry.

OBJECTIVES: To evaluate the effectiveness and safety of pembrolizumab use in advanced melanoma in a real-life context; and to explore the existence of an efficacy-effectiveness gap, comparing registry data with the reference clinical trial. METHODS: This study followed the guidelines for good pharmacoepidemology practice. An ambispective cohort was constituted, initiating the observation upon drug approval (17/07/2015) and following exposed patients until death or cut-off date (15/11/2019). The primary outcome was overall survival (OS); secondary outcomes comprised progression-free survival (PFS), overall response rate (ORR) and the occurrence of adverse events (AE). For all survival analyses, the Kaplan-Meier estimator was used, considering a 95% confidence interval (CI), aside with one-year survival rates. RESULTS: A total of 125 patients constituted the cohort, originating from 16 hospitals in Portugal. Median OS was estimated to be 16.9 months (CI95% 11.3-25.5) and the probability of survival after 1 year was 57.5% (CI95% 48.4%-65.6%). Median PFS was estimated to be 4.8 months (CI95% 3.9-6.7) and the probability of remaining progression-free after 1 year was 32.8% (CI95% 24.8-41.1). ORR was 30.4% (CI95% 22.5%-39.3%). AEs were experienced by 82% of patients, and 27% experienced AE≥ grade 3. CONCLUSIONS: Our data suggest lower effectiveness in a real-life context than the efficacy reported in the clinical trial. Safety data seems, however, quite comparable to KEYNOTE-006.

Real-world effectiveness of pembrolizumab in previously treated non-small cell lung cancer: A population-based cohort study.

PURPOSE: Immunotherapy is promising for lung cancer treatment, although at significant financial impact. The aim of this study was to evaluate the effectiveness and the efficacy-effectiveness gap of pembrolizumab in previously treated non-small cell lung cancer (NSCLC). METHODS: A population-based ambispective cohort study was conducted. Cases of interest were identified through the National Cancer Registry database and additional data sources. Patients aged ≥18 years, diagnosed with NSCLC and exposed to pembrolizumab, between 23 June 2016 and 31 October 2018, as second or later lines of treatment for advanced disease were included. Patients were followed-up until death or cut-off date (30 April 2019). Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), event-free survival (EFS), and adverse events (AEs) leading to treatment discontinuation. The efficacy-effectiveness gap was evaluated comparing results with clinical trial data. RESULTS: A total of 181 patients were included. Median age was 63 years (range 33-94); 74.6% were male. Median treatment duration was 5.6 months (interquartile range: 1.4-10.4) and, at cut-off date, treatment had been discontinued in 141 patients, mainly due to disease progression. Median OS was 13.0 months (95% confidence interval [CI] 9.3-15.9) and 1-year OS was 53.1% (95% CI 45.2%-60.3%). Median PFS was 5.6 months (95% CI 4.6-7.2), median EFS was 4.7 months (95% CI 3.2-6.0), and treatment was discontinued due to AE in 8.3% of cases (n = 15). The efficacy-effectiveness gap seems to favor pembrolizumab use in clinical practice. CONCLUSION: Real-world data suggest the performance of pembrolizumab to reflect the clinical trial outcomes in previously treated NSCLC.

Stroke Severity and Maximum Inspiratory Pressure are Independently Associated with Functional Mobility in Individuals After Stroke.

BACKGROUND: Clinical changes after stroke can contribute to reduced mobility and negatively affect the survival of these individuals. The objective of this study was to verify factors associated with functional mobility in stroke individuals. METHODS: Crosssectional study carried out with stroke individuals in an outpatient clinic. Demographic and clinical data were collected and the following measures were applied: National Institute of Health Stroke Scale (NIHSS), modified Barthel Index, Trunk Impairment Scale, Functional Reach Test, Timed Up and Go Test, and the International Physical Activity Questionnaire. Respiratory muscle strength was assessed by measuring the maximum inspiratory pressure (MIP) and the maximum expiratory pressure (MEP).Variables with p < .05 in univariate logistic regression analysis were included in the multivariate logistic regression model, using the backward stepwise method. RESULTS: 53 individuals were enrolled with a mean age of 55 years (±13.43). 51% were male and the median NIHSS score was 2.25 (0-13). The final multivariate model included NIHSS (OR = 1.872; 95% CI 1.167-3.006; p = 0.009), physical therapy treatment (OR = 15.467; 95% CI 1.838-130.178; p = 0.012) and MIP (OR = 1.078; 95% CI 1.024-1.135; p = 0.004). CONCLUSION: Stroke severity and inspiratory muscle strength were factros associated with functional mobility in individuals after stroke, regardless stroke time.

[Prevalence of Outpatient Use of Medicines by the Elderly Population in Portugal: A Cross-Sectional Study]. / Prevalência da Dispensa de Medicamentos em Ambulatório na População Idosa em Portugal: Um Estudo Transversal.

INTRODUCTION: Like in other countries, the age pyramid in Portugal has been changing considerably, with a substantial increase in the size of the older population and a significant reduction in the number of young people. With aging, co-occurrence of several conditions becomes frequent, often leading to the use of multiple medications (polypharmacy). Polypharmacy in the older population is particularly relevant considering the physiological changes of the ageing process, which increase the risk of drug interactions, poor adherence to treatment, and adverse drug reactions, especially in the oldest-old population (85 years or older). As the size of the older population is likely to increase significantly, it is important to characterize the pattern of medicines' use by the elderly while also identifying cases of polypharmacy in order to obtain evidence that can be used to develop specific measures to tackle the high prevalence of use and its associated risks. To this end, the aim of this study was to characterize medication use by older individuals in Portugal. METHODS: Cross-sectional study with data from the National Health System's Control and Monitoring Center on reimbursed medicines that were prescribed and dispensed to individuals aged 65 years or older in 2019 in all community pharmacies of the Portuguese mainland. We performed a demographic and geographic analysis of the data by international nonproprietary name and therapeutic group. The number of reimbursed packages and the number of reimbursed packages per capita were the metrics used (data from Instituto Nacional de Estatística). RESULTS: A higher consumption of medicines was observed in women, increasing with age, except in the oldest olds, in which the sex difference tended to shrink. Use per capita showed an opposite trend, with the oldest-old men surpassing the oldest-old women (mean reimbursed packages: 55.5 in men versus 55.1 in women). In women, consumption was led by cardiovascular medicines (31%), followed by central nervous system medications (30%) and antidiabetics (13%); in men, 37% of TOP 10 consumption was due to cardiovascular medications, antidiabetics (16%) and drugs for benign prostatic hypertrophy (14%). CONCLUSION: In the elderly, there were sex differences in the pattern of medicines' use, and there were also significant age-related differences in 2019. To the best of our knowledge, our study is the first nationwide analysis of reimbursed medicines' consumption data in the elderly, which is essential to characterize the use of medicines in this age group in Portugal.

Introdução: À semelhança de outros países, a pirâmide etária em Portugal tem sofrido alterações profundas, com um expressivo aumento na dimensão da população idosa. A multimorbilidade que surge com o envelhecimento leva, frequentemente, à utilização concomitante de vários medicamentos. A polimedicação é particularmente importante no idoso devido às alterações fisiológicas associadas ao processo de envelhecimento, que aumentam o risco de interações medicamentosas, de fraca adesão à terapêutica e de reações adversas à medicação, em particular nos indivíduos muito idosos (85 ou mais anos). Dado que a dimensão da população idosa poderá aumentar significativamente, importa caracterizar o padrão de consumo de medicamentos pelos idosos, identificando também os casos de polifarmácia, de forma a gerar-se evidência que permita o desenvolvimento de medidas específicas de combate à elevada prevalência de utilização e riscos associados. Assim, o objetivo desta análise preliminar foi determinar a prevalência e caracterizar do padrão de utilização de medicamentos pelos idosos em Portugal, desagregando por faixa etária, sexo e localização geográfica. Métodos: Estudo transversal com dados relativos aos medicamentos comparticipados e dispensados nas farmácias comunitárias de Portugal Continental em 2019, aos utentes com mais de 65 anos. Efetuou-se análise descritiva demográfica e geográfica, por denominação comum internacional e grupo terapêutico. A utilização foi estudada através do número de embalagens comparticipadas dispensadas e número de embalagens comparticipadas dispensadas per capita (dados do Instituto Nacional de Estatística). Resultados: Observou-se uma dispensa superior nas mulheres, a qual foi aumentando com a idade, à exceção dos idosos 85+, nos quais a diferença tendeu a diminuir. No que diz respeito ao número de embalagens comparticipadas dispensadas per capita, a tendência foi inversa, com os homens muito idosos a ultrapassarem as mulheres 85+ (média de embalagens: 55,5 nos homens versus 55,1 nas mulheres). Nas mulheres, os medicamentos mais consumidos foram os do foro cardiovascular (31%), seguidos dos prescritos para o sistema nervoso central (30%) e antidiabéticos (13%). Nos homens, o ranking foi liderado também pelos medicamentos para o aparelho cardiovascular (37%); contudo, em segundo lugar surgem os antidiabéticos (16%), seguidos dos medicamentos para a hiperplasia benigna da próstata (14%). Conclusão: Existiram diferenças de sexo e idade relevantes no padrão de dispensa de medicamentos comparticipados nos idosos portugueses em 2019. Esta é a primeira análise publicada de âmbito nacional à dispensa de medicamentos em idosos, sendo essencial para caracterizar o perfil de utilização de medicamentos pelos seniores em Portugal.

Real-world effectiveness of palbociclib plus fulvestrant in advanced breast cancer: Results from a population-based cohort study.

BACKGROUND: Real-world (RW) data may provide valuable information on the effectiveness and safety of medicines, which is particularly relevant for clinicians, patients and third-party payers. Evidence on the effectiveness of palbociclib plus fulvestrant is scarce, which highlights the need of additional studies. The aim of this study was to evaluate the effectiveness of palbociclib plus fulvestrant in advanced breast cancer (ABC). MATERIALS AND METHODS: We conducted a population-based retrospective cohort study and cases of interest were identified through the Portuguese National Cancer Registry database and additional data sources. Patients aged≥18 years, diagnosed with ABC and exposed to palbociclib plus fulvestrant between May 31, 2017 and March 31, 2019 were included. Patients were followed-up until death or cut-off date (February 28, 2021). Primary outcome was rw-progression-free survival (rwPFS). Secondary outcomes were rw-overall survival (rwOS), rw-time to palbociclib failure (rwTPF) and rw-time to next treatment (rwTTNT). RESULTS: A total of 210 patients were included. Median age was 58 years (range 29-83) and 99.05% were female. Median follow-up time was 23.22 months and, at cut-off date, treatment had been discontinued in 189 patients, mainly due to disease progression (n = 152). Median rwPFS was 7.43 months (95% confidence interval [CI] 6.28-9.05) and 2-year rwPFS was 16.65% (95%CI 11.97-22.00). Median rwOS was 24.70 months (95%CI 21.58-29.27), median rwTPF was 7.5 months (95%CI 6.51-9.08) and median rwTTNT was 11.74 months (95%CI 10.33-14.08). CONCLUSION: Palbociclib plus fulvestrant seems an effective treatment for ABC in real-world context. Compared to registrations studies, rwPFS and rwOS were shorter in real-life setting.

Cross-national comparison of paediatric antibiotic use in Norway, Portugal and Hungary.

A cross-national comparison was performed on paediatric (0-19 years) antibiotic use in Hungary, Norway and Portugal to explore and compare the scale and pattern of paediatric antibiotic use in these three European countries. Ambulatory care systemic antibiotic use (ATC: J01) was retrieved from national databases for year 2014. The main outcome measure was number of antibacterial packages per child inhabitant per year (packages/child/year) and was further stratified by age groups. Paediatric antibiotic use peaked in Hungary with 1.3 packages/child/year, followed by Portugal (0.8) and Norway (0.3). This ranking was retained and was most prominent in the 5- to 9-year and 10- to 14-year age groups. The pattern of antibiotic use in different paediatric age groups varied also substantially between countries. Narrow-spectrum penicillins were much commonly used in Norway in all paediatric age subgroups in comparison with Hungary and Portugal. Newer, broad-spectrum cephalosporins and macrolides were widely prescribed for Hungarian and Portuguese children in all paediatric subgroups in contrast to Norway, while tetracyclines were commonly prescribed for Norwegian adolescents. The scale and pattern of paediatric antibiotic use in Hungary and Portugal were very different compared with Norway. The high antibiotic exposure and the high consumption of broad-spectrum penicillins begin in childhood in Hungary and Portugal which underpins the responsibility of paediatric GPs.

Vulnerabilidade clínico-funcional de idosos acompanhados por uma unidade de cuidados primários à saúde / Clinical-functional vulnerability of older adults assisted in a primary health care unit

OBJETIVO: Identificar os fatores associados à condição de vulnerabilidade clínico-funcional de idosos soteropolitanos acompanhados em uma unidade de cuidados primários à saúde. MÉTODOS: Estudo transversal conduzido com pessoas com idade igual ou superior a 60 anos cadastradas em uma unidade docente-assistencial em Salvador, Bahia. Foram excluídas as que não tinham histórico de acompanhamento regular ambulatorial ou com prontuário inativo há mais de cinco anos. Foram coletados dados sociodemográficos e aplicado o Índice de Vulnerabilidade Clínico Funcional (IVCF-20) entre novembro de 2019 a março de 2021. Os idosos foram classificados como robustos ou não-robustos e análises bivariadas foram realizadas com o intuito verificar as diferenças entre os grupos. As variáveis que apresentaram associações com p<0,10 foram incluídas no modelo regressão de Poisson e foram feitos os ajustes para possíveis confundidores. RESULTADOS: Participaram do estudo 102 idosos e foi verificado que a capacidade aeróbica e/ou muscular comprometida (RP=2,91; IC95% 1,50 ­6,18), a presença de comorbidades múltiplas (RP=2,79; IC95% 1,51­ 5,48), a incontinência esfincteriana (RP=1,86; IC95% 1,04 ­ 3,30) e a piora do esquecimento (RP=1,88; IC95% 1,04 ­ 3,55) foram os fatores independentemente associados à vulnerabilidade clínicofuncional. CONCLUSÃO: Os resultados do estudo permitem concluir que o comprometimento da capacidade aeróbica, a presença de comorbidades múltiplas, incontinência esfincteriana e perda de memória encontram-se associados à condição de vulnerabilidade clínico-funcional de idosos soteropolitanos acompanhados por uma unidade de cuidados primários à saúde. Essas informações devem ser consideradas no planejamento dos cuidados no âmbito da Atenção Primária à Saúde e da atenção integral.

OBJECTIVE: To identify the factors associated with the condition of clinical-functional vulnerability of elderly people in Salvador followed in a primary health care unit. METHODS: Crosssectional study conducted with people aged 60 or over registered in a teaching-assistance unit in Salvador, Bahia. Those who had no history of regular outpatient follow-up or had inactive medical records for more than five years were excluded. Sociodemographic data were collected and the Clinical-Functional Vulnerability Index (IVCF-20) was applied between November 2019 and March 2021. The elderly were classified as robust or non-robust and bivariate analyzes were carried out with the aim of verifying the diferences between the groups. The variables that presented associations with p<0.10 were included in the Poisson regression model and adjustments were made for possible confounders. RESULTS: 102 elderly people participated in the study and it was found that their aerobic and/or muscular capacity was compromised (RP=2.91; IC95% 1.50 ­ 6.18), the presence of multiple comorbidities (PR=2.79; IC95 % 1.51 ­ 5.48), sphincter incontinence (RP=1.86; 95%CI 1.04 ­ 3.30) and worsening forgetfulness (PR=1.88; 95%CI 1.04 ­ 3, 55) were the factors independently associated with clinical-functional vulnerability. CONCLUSION: The results of the study allow us to conclude that the impairment of aerobic capacity, the presence of multiple comorbidities, sphincter incontinence and memory loss are associated with the condition of clinical-functional vulnerability of elderly people in Salvador accompanied by a primary health care unit. This information must be considered when planning care within the scope of Primary Health Care and comprehensive care.

Proposal for a regulation on health technology assessment in Europe - opinions of policy makers, payers and academics from the field of HTA.

INTRODUCTION: In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): 'Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU'. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States. Areas covered: This paper presents the consolidated views and considerations on the original Proposal as set by the European Commission of a number of policy makers, payers, experts from pricing and reimbursement authorities and academics from across Europe. Expert commentary: The Proposal has since been extensively discussed at Council and while good progress has been achieved, there are still divergent positions. The European Parliament gave a number of recommendations for amendments. If the Proposal is approved, it is important that a balanced, improved outcome is achieved for all stakeholders. If not approved, the extensive contribution and progress attained should be sustained and preserved, and the best alternative solutions found.

Rational use of blood glucose test strips for self-monitoring in patients with diabetes mellitus: Economic impact in the Portuguese healthcare system.

AIMS: Self-monitoring of blood glucose is important for diabetes management in insulin-treated patients, but its effectiveness in patients treated with oral glucose lowering drugs only is not fully supported by current evidence. This paper aims to characterise the prescription patterns of blood glucose test strips (BGTS) in Portugal and estimate the potential cost-savings from the rational use of BGTS. METHODS: A retrospective analysis of the Portuguese database of electronic medical prescriptions to assess the patterns of BGTS prescription. The database was searched for prescription, from 01 January 2016 to 31 December 2016, of insulin and other antidiabetics, as well as the associated prescriptions of BGTS. RESULTS: 894,637 patients were prescribed antidiabetic medicines during 2016, 82.7% of which were prescribed oral glucose lowering drugs only. BGTS were prescribed to 456,179 patients, being more frequently prescribed in insulin-treated patients. Still, 42.8% of patients treated with oral glucose lowering drugs only were also prescribed BGTS, with large proportion of those being prescribed antidiabetic drugs with lower risk of causing hypoglycaemia and, even so, >200 BGTS/year. Several scenarios for a more rational use of BGTS were estimated to result in cost-savings of up to €9.5 million per year. CONCLUSIONS: BGTS were prescribed to more than a third of patients treated with oral glucose lowering drugs only, despite accumulating evidence of their limited effectiveness in this population, resulting in substantial economic burden to the healthcare system. Given the estimated potential cost-savings, rational use of BGTS should be encouraged in Portugal.

Anti-hypertensive drug utilization in Continental Portugal (1999-2004).

INTRODUCTION: The estimated prevalence of arterial hypertension (HT) in Portugal in 2003 was 43%, with only 28.8% of patients undergoing antihypertensive treatment having their blood pressure controlled. In the light of this fact, if HT is detected early and adequately controlled, there is great potential for reducing cardiovascular morbidity and mortality. OBJECTIVES: This study aimed to analyze patterns of antihypertensive drug utilization in Portugal at the regional and national level, to compare them with other countries, and to evaluate trends in certain indicators regarding use of these drugs. METHODS: Data on antihypertensive drug utilization refer to drugs prescribed and dispensed in the ambulatory population covered by the Portuguese national health service, from January 1, 1999 to June 30, 2004. Data were expressed in defined daily doses (DDD) per 1000 inhabitants per day (DID). RESULTS: Use of antihypertensives increased from 183 DID in the first half of 1999 to 256 DID in the first half of 2004, an increase of 40%. Angiotensin-converting enzyme inhibitors were the most frequently prescribed drug class, being used by 31% of the study population, followed by diuretics (16%) and calcium channel blockers (14%). Angiotensin receptor blockers (ARBs) accounted for most of the growth in antihypertensive use, although they represent the most expensive therapeutic option. This pattern of use had a strong impact on antihypertensive drug expenditure, which increased 60% over the study period. ARBs, plain or in combination formulations, accounted for 55% and 71% of the increase in utilization and expenditure respectively. DISCUSSION: From the standpoint of health gains, the significant rise in antihypertensive drug utilization represents a potentially favorable development in terms of increased numbers of patients undergoing drug treatment. Compared to other European countries, the data showed greater use of drugs that act on the renin-angiotensin system in Portugal and less use of diuretics and beta-blockers. Most national and international guidelines recommend diuretics as first-line agents in HT treatment. Considering that these drugs have the lowest daily treatment cost, a high, and increasing, rate of utilization would be expected, but this is not the case in Portugal. CONCLUSIONS: This study reveals not only significant differences in antihypertensive drug utilization at the regional level in Portugal but also a lack of adherence to national and international guidelines, and therefore more attention should be paid to their implementation in order to improve health gains.

Increased intracranial volume: a clue to the etiology of idiopathic normal-pressure hydrocephalus?

BACKGROUND AND PURPOSE: The etiology of idiopathic normal-pressure hydrocephalus (NPH) is unknown. The purpose of this study was to examine the hypothesis that NPH begins in infancy as benign external hydrocephalus due to decreased uptake of CSF by the arachnoid villi. Since this occurs before the sutures fuse, a secondary hypothesis is that the intracranial volumes of patients with NPH should be larger than those of healthy individuals. METHODS: Intracranial volumes of 51 patients with clinically suspected NPH were compared with those of age- and sex-matched control subjects. All patients underwent phase-contrast CSF velocity MR imaging. They had aqueductal CSF stroke volumes of at least 60 microL, which was 50% higher than previously published normal values. Intracranial volumes were measured and compared between groups. RESULTS: The average intracranial volume for men with NPH (n = 22) was 1682 mL compared with 1565 for male control subjects (n = 55). The NPH volume averaged 118 mL (7.5%) larger than the control volume (P = .003). The average intracranial volume for women with NPH (n = 29) was 1493 mL compared with 1405 mL for female control subjects (n = 55). The NPH volume was 88 mL (6.3%) larger than the control volume (P = .002). CONCLUSION: Patients with NPH have intracranial volumes significantly larger than normal, suggesting that the initial insult occurs before the sutures fuse at 1 year of age. The patients somehow remain asymptomatic until their later years, when a second insult must occur, leading to symptomatic NPH.

Association between cardiovascular disease and socioeconomic level in Portugal.

INTRODUCTION: Cardiovascular disease is the leading cause of morbidity, mortality and disability in Portugal. Socioeconomic level is known to influence health status but there is scant evidence on socioeconomic inequalities in cardiovascular disease in Portugal. AIM: To analyze the distribution of cardiovascular disease in the Portuguese population according to socioeconomic status. METHODS: We conducted a cross-sectional study using data from the fourth National Health Survey on a representative sample of the Portuguese population. Socioeconomic inequalities in cardiovascular disease, risk factors and number of medical visits were analyzed using odds ratios according to socioeconomic status (household equivalent income) in the adult population (35-74 years). Comparisons focused on the top and bottom 50% and 10% of household income distribution. RESULTS: Of the 21 807 individuals included, 53.3% were female, and mean age was 54 ± 11 years. Cardiovascular disease, stroke, ischemic heart disease, hypertension, diabetes, obesity and physical inactivity were associated with lower socioeconomic status, while smoking was associated with higher status; number of medical visits and psychological distress showed no association. When present, inequality was greater at the extremes of income distribution. CONCLUSIONS: The results reveal an association between morbidity, lifestyle and socioeconomic status. They also suggest that besides improved access to effective medical intervention, there is a need for a comprehensive strategy for health promotion and disease prevention that takes account of individual, cultural and socioeconomic characteristics.

[Benzodiazepine's utilization in continental Portugal (1999-2003)]. / Utilização de benzodiazepinas em Portugal continental (1999-2003).

INTRODUCTION: Portugal has one of the highest levels of benzodiazepine's utilization at European level. This issue was highlighted on the latest International Narcotics Control Board report, which advises Portugal to analyse the actual procedures on prescription and utilization of these drugs. This study aimed to analyse Portuguese benzodiazepine's utilization patterns and trends at regional and national level, and analyse its relation with factors known to affect the utilization of these drugs. METHODOLOGY: Drug utilization data refers to the drugs prescribed and dispensed in the ambulatory to the population covered by the National Health Service, from 1st January 1999 to 31st December 2003. Data was expressed in Defined Daily Dose (DDD) per 1000 inhabitants per day (DHD). RESULTS: In the Portuguese National Health Service during the period in study there was a decrease of 1.2% on benzodiazepine's utilization. Nevertheless, it was observed an increase on anxyolitics benzodiazepine's utilization (3.8%;72.66 DHD), although hypnotics benzodiazepine's suffered a marked decrease (-21.9%;13.15 DHD). The expenditure has not followed the utilization's trend, and in the period in study the retail sale price expenditure increased 12%. Anxyolitic benzodiazepine's utilization accounted for 85% of the growth on expenditure observed in this study. At national level there were some asymmetries either on utilization's level or on drug utilization's pattern. In 2003, Faro, Bragança and Viana do Castelo were the sub-regions with the lowest utilization level and Portalegre and Evora the ones with the highest levels. Lisbon presented the highest decrease either on percentual (-13.8%) or on absolute (-13.45 DHD) values. DISCUSSION: Benzodiazepine's utilization in Portugal was considered of concern by International Narcotics Control Board. Therefore the stabilization on utilization, with even a small decrease, should be considered potentially positive. The asymmetries either on utilization's level or on drug utilization's pattern do not seem to be totally attributable to age-structure, unemployment levels or the percentage of retired people, as there wasn't a statistical significant relation between these variables. For this reason the variations on Benzodiazepine's utilization in Portugal seem to be attributed to a combination of different factors, which emphasize the need of more initiatives conducted to health care professionals and patients, in order to diminish the chronic use of these drugs.

[Information sources and prescribing in the Lisbon region]. / Fontes de informação e prescrição médica na região de Lisboa.

INTRODUCTION: Quality in prescribing and rational use of drugs requires that physicians are kept up to date with developments in the medical literature and have knowledge of newly available drugs. This study aimed to examine, quantitatively, the sources of drug information that are used by physicians and to verify if there are differences according to work setting, namely health centers and hospitals. METHODS: Cross-sectional descriptive analysis based on the application of a self-administered anonymous questionnaire developed specifically for the study. The 71 physician respondents were drawn from one public hospital (60.9%) and three public health centers (39.1%) in the Lisbon region. Respondents were asked to rate information sources in terms of their importance for prescribing and to report their use of these sources both in their general drug adoption procedures, in the adoption of one of a number of target 'new' drugs and in the evaluation of the therapeutic, pharmacological and economic value of drugs. RESULTS: Commercial sources were cited more frequently than professional or official sources of information in the process of adopting new drugs for prescribing. In evaluating the therapeutic and economic value of a new drug, doctors used primarily studies disseminated by the pharmaceutical industry. Official sources of information were only used widely in case of uncertainties in the dose and dose regime of drugs. The use of sources of information varied with physician's characteristics and with the place of work, with primary care doctors revealing more frequent use of commercial sources. CONCLUSION: Doctors working in hospitals and health centers use commercial sources above all others. There are, however, some differences according to work setting. In combining scientific information with interpersonal communication, the pharmaceutical industry appears to have a more effective strategy for communicating information to doctors. Health authorities should take this knowledge on board when drawing up strategies for improving the quality of prescribing, thereby assuring that the best quality information is used in clinical practice.

Whole-body CT screening: spectrum of findings and recommendations in 1192 patients.

PURPOSE: To retrospectively determine the frequency and spectrum of findings and recommendations reported with whole-body computed tomographic (CT) screening at a community screening center. MATERIALS AND METHODS: This HIPAA-compliant study received institutional review board approval, with waiver of informed consent. The radiologic reports of 1192 consecutive patients who underwent whole-body CT screening of the chest, abdomen, and pelvis at an outpatient imaging center from January to June 2000 were reviewed. Scans were obtained with electron-beam CT without oral or intravenous contrast material. Reported imaging findings and recommendations were retrospectively tabulated and assigned scores. Descriptive statistics were used (means, standard deviations, and percentages); comparisons between subgroups were performed with univariate analysis of variance and chi(2) or Fisher exact tests. RESULTS: Screening was performed in 1192 patients (mean age, 54 years). Sixty-five percent (774 of 1192) were men and 35% (418 of 1192) were women. Nine hundred three (76%) of 1192 patients were self referred, and 1030 (86%) of 1192 subjects had at least one abnormal finding described in the whole-body CT screening report. There were a total of 3361 findings, with a mean of 2.8 per patient. Findings were described most frequently in the spine (1065 [32%] of 3361), abdominal blood vessels (561 [17%] of 3361), lungs (461 [14%] of 3361), kidneys (353 [11%] of 3361), and liver (183 [5%] of 3361). Four hundred forty-five (37%) patients received at least one recommendation for further evaluation. The most common recommendations were for additional imaging of the lungs or the kidneys. CONCLUSION: With whole-body CT screening, findings were detected in a large number of subjects, and most findings were benign by description and required no further evaluation. Thirty-seven percent of patients had findings that elicited recommendations for additional evaluation, but further research is required to determine the clinical importance of these findings and the effect on patient care.