Ophthalmic adverse drug reactions to systemic drugs: a systematic review.

PURPOSE: To perform a comprehensive and systematic review regarding ophthalmic adverse drug reactions (ADRs) to systemic drugs to: (i) systematically summarize existing evidence, (ii) identify areas, ophthalmic ADRs or drugs that lacked systematization or assessment (namely drugs with original studies characterizing specific ophthalmic ADRs but without causality assessment nor without meta-analysis). METHODS: Systematic review of several electronic databases (last search 1/7/2012): Medline, SCOPUS, ISI web of knowledge, ISI Conference Proceedings, International Pharmaceutical Abstracts and Google scholar. Search query included: eye, ocular, ophthalmic, ophthalmology, adverse and reaction. Inclusion criteria were: (i) Primary purpose was to assess an ophthalmic ADR to a systemic medication; (ii) Patient evaluation performed by an ophthalmologist; (iii) Studies that specified diagnostic criteria for an ocular ADR. Different types of studies were included and analyzed separately. Two independent reviewers assessed eligibility criteria, extracted data and evaluated risk of bias. RESULTS: From 562 studies found, 32 were included (1 systematic review to sildenafil, 11 narrative reviews, 1 trial, 1 prospective study, 6 transversal studies, 6 spontaneous reports and 6 case series). Drugs frequently involved included amiodarone, sildenafil, hydroxychloroquine and biphosphonates. Frequent ophthalmic ADRs included: keratopathy, dry eye and retinopathy. CONCLUSIONS: To increase evidence about ophthalmic ADRs, there is a need for performing specific systematic reviews, applying strictly the World Health Organization's (WHO) definition of ADR and WHO causality assessment of ADRs. Some ophthalmic ADRs may be frequent, but require ophthalmological examination; therefore, ophthalmologists' education and protocols of collaboration between other specialties whenever they prescribe high-risk drugs are suggestions for the future.

A survey of spontaneous reporting of adverse drug reactions in 10 years of activity in a pharmacovigilance centre in Portugal.

OBJECTIVE: Reporting of adverse drug reactions (ADRs) may differ between countries. METHODS: In a retrospective descriptive study we analysed the potential causative drugs and clinical situations related to spontaneously reported ADRs over 10 years to a regional pharmacovigilance centre in Portugal. KEY FINDINGS: We collected 3165 cases (36% of all national reports) of ADRs reported by doctors (54%), pharmacists (31%), and nurses (15%), 56% of which were classified as serious, 22% as unexpected and 13% as both serious and unexpected. According to World Health Organization causality criteria of ADRs related to drugs, 67% where probable, 20% possible, 7% conditional, 6% certain and 1% unclassifiable or unlikely. There was a predominance of females (66%, P < 0.005) both for total and serious ADRs. Physicians, while working in hospitals, reported more (68%) and more serious ADRs (75%) than those working in primary care (29%). Pharmacists working outside hospitals reported more (90%) than those working in hospitals. Drugs more frequently associated with ADRs were antibiotics (22%), followed by vaccines (16%), drugs acting on the nervous system (15%), non-steroidal anti-inflammatory drugs (14%) and those working on the cardiovascular system (11%). The most common systems, organs or disorders affected by ADRs were skin manifestations (21%), followed by general disorders (20%), gastrointestinal/hepatobiliary disorders (15%), nervous system disorders (11%) and immune system disorders (6%). CONCLUSIONS: Our study shows a general commitment of Portuguese health professionals to ADR reporting with a clear predominance of serious rather than non-serious ADRs. This study may help to improve the recognition of the general aspects of ADRs occurring in Portugal.

Detection of adverse drug reactions using hospital databases-a nationwide study in Portugal.

PURPOSE: This study aimed to detect and characterize adverse drug reactions (ADRs) that occurred during hospitalization (ADRIn ) and ADRs associated with admission (ADRAd ) in Portugal from 2000 to 2009. We also intended to compare the results of this methodology with spontaneous reporting. METHODS: We conducted a nationwide study using a hospital administrative database that included all acute care public hospitalizations in Portugal, from 2000 to 2009. We used International Classification of Diseases-9(th) Revision-Clinical Modification coding data for the detection of ADRs. Codes searched included "E" codes (E930 to E949.9, codes that exclude poisonings and errors) and five groups of diagnoses codes associated with high prevalence of ADR as found in a previous study: hypoglycemia, drug-induced neutropenia, hepatitis unspecified, anaphylactic shock due to drugs, and shock due to anesthesia. RESULTS: From 9 271 122 hospitalizations within that period, 116 720 ADRs were detected through the database methodology, representing 1.26% from all hospitalizations. Of the ADRs, 97.3% occurred during hospitalization (ADRIn ), whereas 2.7% were associated with admission. Age, female sex, and comorbidities such as pneumonia, heart failure, diabetes, and malignancies were associated with ADRs (all with differences statistically significant). There were 13 562 spontaneous reports from 2000 to 2009. CONCLUSIONS: Several methods have been used for the detection of ADRs, but they are difficult to apply at a national level. Spontaneous reporting is widely used but grossly underestimates the frequency of ADRs. The database methodology can be very useful to estimate ADRs frequency and to perform a simple characterization of ADRs nationwide.

Methodologies for the detection of adverse drug reactions: comparison of hospital databases, chart review and spontaneous reporting.

PURPOSE: To evaluate a methodology for adverse drug reactions (ADRs) detection through hospital databases. METHODS: A retrospective analysis was conducted to identify ADRs using diagnostic codes from databases, later validated by chart review. An independent chart review was performed for comparison, as well as assessment of spontaneous reports. RESULTS: 325 ADRs were identified (prevalence of 2.41%, positive predictive value of 87.6%). Independent chart review identified 9% of ADRs at a cost of 35 person-hours (versus two person-hours in databases). There were seven spontaneous reports of ADRs. CONCLUSIONS: Although not frequently used, the detection of ADRs through databases is a relatively less expensive, fast and effective methodology that can improve current pharmacovigilance systems.

Frequency of adverse drug reactions in hospitalized patients: a systematic review and meta-analysis.

PURPOSES: To perform a comprehensive systematic review of prospective studies about frequency of adverse drug reactions (ADRs) occurring during hospitalization (ADR(In) ), including a thorough study quality assessment, meta-analysis and heterogeneity evaluation. METHODS: Systematic review of several databases: Pubmed, EMBASE, CINAHL, Cochrane, ISI, International Pharmaceutical Abstracts, Scirus, NHS economic, and others, as well as manual search. Inclusion criteria were: prospective studies (assessing all patients before discharge, by a specialized team, at least once a week); with data about ADRs occurring during hospitalization, using WHO's or similar definition of ADR. Two independent reviewers assessed eligibility criteria, extracted data, and evaluated risk of bias. RESULTS: From 4139 studies initially found, 22 were included. Meta-analysis indicate that ADRs may occur in 16.88% (CI95%: 13.56,20.21%) of patients during hospitalization; however, this estimate has to be viewed with caution because there was significant heterogeneity (I² = 99%). The most significant moderators of heterogeneity were risk of bias, population, ward, and methodology for ADR identification. Low risk of bias studies adjusted for population (pediatric versus adult) had I² = 0%. CONCLUSIONS: These data are useful as a broad characterization of in-hospital ADRs and their frequency. However, due to heterogeneity, our estimates are crude indicators. The wide variation in methodologies was one of the most important moderators of heterogeneity (even among studies using intensive monitoring). We suggest criteria to standardize methodologies and reduce the risk of bias.

[Analysis of maternal and child health indicators: the parallel between Portugal and Brazil]. / Análise de indicadores da saúde materno-infantil: paralelos entre Portugal e Brasil.

PURPOSE: To analyze comparatively the conditions of birth in Portugal and Brazil from 1975 to 2007. METHODS: Indicators of maternal and child health: rates of maternal death and neonatal mortality, cesarean rate and public spending on health were retrospectively collected from electronic databases of health information from the Unified Health System (DATASUS) and the National Institute of Statistics of Portugal (INE), among others. Their values were descriptively analyzed in terms of trends and the temporal sanitary scenarios were presented and discussed, comparing, when possible, the information from the two countries. RESULTS: Births in Portugal were characterized by lower maternal mortality (12.2 x 76.2/100.000) and neonatal mortality (2.2 x 14.6/1000), compared to Brazil, considering the average of the years from 2004 to 2007. The history of the conquest of maternal and child indicators of excellence in Portugal involved a phase that paralleled the significant socio-economic improvements and the increasing contribution of public health, followed by another from the 1990 s, involving better equipped health care units. In Brazil, rates of maternal and neonatal mortality are declining, but satisfactory values have not yet been achieved. The historical difference in the amount of social spending on health, both in current and historical values, was a crucial difference between countries. Despite the disparities in maternal and neonatal outcomes, cesarean section rates were equally ascendant (34.5% in Portugal and 45.5% in Brazil), considering the average for the period from 2004 to 2007. CONCLUSION: The indicators of maternal and neonatal death in Portugal and Brazil have aligned themselves to social, economic and contributions of public investments in health. The increasing rates of caesarean section do not explain the discrepancies in maternal and neonatal outcome between countries.

Análise de indicadores da saúde materno-infantil: paralelos entre Portugal e Brasil / Analysis of maternal and child health indicators: the parallel between Portugal and Brazil

OBJETIVO: Analisar comparativamente as condições de nascimento em Portugal e no Brasil, no período entre 1975 a 2007. MÉTODOS: Os indicadores de saúde materno-infantis, razão de morte materna, mortalidade neonatal, taxa de cesarianas e gastos públicos em saúde, foram retrospectivamente coletados nas bases eletrônicas de informação do Sistema Único de Saúde (DATASUS), Instituto Nacional de Estatística de Portugal (INE), entre outras. Seus valores foram analisados descritivamente quanto a sua tendência e os cenários sanitários nos quais transcorreram foram apresentados e discutidos, comparando-se, sempre que possível, as informações dos dois países. RESULTADOS: Os nascimentos em Portugal caracterizaram-se por baixa mortalidade materna (12,2x76,2/100.000) e mortalidade neonatal (2,2x14,6/1000), comparativamente ao Brasil, na média dos anos 2004 a 2007. O histórico da conquista de indicadores materno-infantis de excelência em Portugal envolveu uma fase que transcorreu paralela às expressivas melhorias socioeconômicas e ao aporte crescente de recursos públicos em saúde, seguida de outra a partir da década de 1990, simultânea ao melhor aparelhamento das unidades de assistência à saúde. No Brasil, os índices de mortalidade materna e neonatal estão em queda, mas valores satisfatórios ainda não foram conquistados. A diferença histórica no montante do gasto público em saúde foi uma discrepância importante entre os países. A despeito das disparidades nos resultados maternos e neonatais, as taxas de cesariana mostraram-se igualmente ascendentes (34,5 por cento em Portugalx45,5 por cento no Brasil), na média do período 2004 a 2007. CONCLUSÃO: Os indicadores da morte materna e neonatal em Portugal e no Brasil alinharam-se às diferenças sociais, econômicas e aos aportes de investimentos públicos em saúde. As crescentes taxas de cesariana não explicam as discrepâncias no resultado materno e neonatal entre os países.

PURPOSE: To analyze comparatively the conditions of birth in Portugal and Brazil from 1975 to 2007. METHODS: Indicators of maternal and child health: rates of maternal death and neonatal mortality, cesarean rate and public spending on health were retrospectively collected from electronic databases of health information from the Unified Health System (DATASUS) and the National Institute of Statistics of Portugal (INE), among others. Their values were descriptively analyzed in terms of trends and the temporal sanitary scenarios were presented and discussed, comparing, when possible, the information from the two countries. RESULTS: Births in Portugal were characterized by lower maternal mortality (12.2x76.2/100.000) and neonatal mortality (2.2x14.6/1000), compared to Brazil, considering the average of the years from 2004 to 2007. The history of the conquest of maternal and child indicators of excellence in Portugal involved a phase that paralleled the significant socio-economic improvements and the increasing contribution of public health, followed by another from the 1990s, involving better equipped health care units. In Brazil, rates of maternal and neonatal mortality are declining, but satisfactory values have not yet been achieved. The historical difference in the amount of social spending on health, both in current and historical values, was a crucial difference between countries. Despite the disparities in maternal and neonatal outcomes, cesarean section rates were equally ascendant (34.5 percent in Portugal and 45.5 percent in Brazil), considering the average for the period from 2004 to 2007. CONCLUSION: The indicators of maternal and neonatal death in Portugal and Brazil have aligned themselves to social, economic and contributions of public investments in health. The increasing rates of caesarean section do not explain the discrepancies in maternal and neonatal outcome between countries.

Association of anxiety with asthma: subjective and objective outcome measures.

BACKGROUND: The relationship between anxiety and asthma is currently being intensively studied. OBJECTIVE: The authors examined anxiety that influences and is influenced by this complex disease. METHOD: The authors conducted a cross-sectional study of adults with asthma at a hospital outpatient department, excluding known psychiatric patients. A sample of 195 patients, mostly middle-aged women with moderate/severe asthma, underwent pulmonary function and airway-inflammation tests and were given anxiety rating questionnaires. RESULTS: A high level of anxiety was present in 70% of the patients. Anxiety was associated with worse subjective asthma outcomes and increased use of medication/healthcare services, but with decreased airway inflammation, and was not associated with lung function. CONCLUSION: Anxiety seems to influence patients' perception/awareness of asthma symptoms.