Incidence and reasons for discontinuation of first-line therapy in patients with multiple myeloma: results from a historical cohort, Brazil 2009-2020.

Multiple myeloma (MM) is an incurable hematological cancer requiring multiple lines of anti-myeloma regimens to promote disease remission and increase patient survival. The study assessed the incidence and reasons for discontinuation of first-line therapy in outpatients who started MM therapy in Belo Horizonte, Brazil from 2009 to 2020. A historical cohort study in which patients were followed from treatment initiation until discontinuation of first-line therapy. Discontinuation of first-line therapy was characterized as (i) discontinuation followed by a second-line therapy, and (ii) discontinuation that prevented patients from receiving a subsequent line of treatment. Non-parametric competing risk analysis with a 95% confidence interval estimated the cumulative incidences of discontinuation followed by a second-line therapy. The probability of discontinuation was compared according to selected variables using the Gray's test at a significance level of 5%. Approximately half of the participants (n = 260) were female and younger than 65 years. Discontinuation of first-line therapy followed by a second-line therapy accounted for 50.4% of the patients and occurred up to 30th month. The main reason for discontinuation not qualifying patients for receiving second-line therapy was to achieve a response to treatment. The maximum times for discontinuation not followed by a second-line therapy ranged from 12 to 20 months due to deaths or response to treatment. The probability of receiving second-line therapy was higher among patients initiating therapy in 2009-2014 and those not undergoing transplantation. In conclusion, discontinuation of first-line therapy followed by second-line treatment occurred as likely as the discontinuation not followed by a subsequent line.

Real-world effectiveness and safety of multiple myeloma treatments based on thalidomide and bortezomib: A retrospective cohort study from 2009 to 2020 in a Brazilian metropolis.

BACKGROUND: Multiple myeloma (MM) is an incurable cancer of plasma cells; the survival of which has improved over the years with the emergence of new treatments. In Brazil, the availability of treatment-regimens is different from developed countries. Real-world evidence with Brazilian patients is lacking. OBJECTIVES: Our aim was to evaluate the effectiveness and the safety of MM treatments in a Brazilian metropolis. METHODS: This was a retrospective cohort study with MM patients, beginning MM treatment from 2009 to 2020 (i.e., before bortezomib became available in public health services). Patients' medical records were revised to obtain clinical variables. The primary outcomes were Overall Survival (OS) and Progression Free Survival (PFS, measured as time to next treatment), and the secondary outcomes were Adverse Events (AE). Kaplan-Meier curves were obtained and the Cox proportional hazards model was performed for univariate and multivariate analyses. The incidence of AE was estimated and the chi-squared test was performed to evaluate the association between AE and MM regimens. RESULTS: In total, 278 patients participated in the study with median age of 64 years; 50.4 % were females, 55.8 % attended a private clinic, 34.9 % received autologous stem cell transplantation (ASCT) and 32.4 % were on polypharmacy. Most patients from public services used thalidomide-based regimens (40.3 %) and at private clinics used bortezomib-based regimens (38.1 %) as first-line treatment. Patients had a median OS of 99 months. Patients had median PFS of 28 months in first-line treatment, which was significantly different for age (p = 0.0055), polypharmacy (p = 0.0094) and ASCT (p < 0.0001). PFS was independently associated to polypharmacy and ASCT. The incidence of peripheral neuropathy (39.6 %) was high. In contrast, the incidence of severe AE was low. We found significant difference between first-line T + B-based regimens and leukopenia (p = 0.012). CONCLUSION: Our study showed that patients on polypharmacy and who did not receive ASCT had worse PFS. Similar to other Latin countries, most patients used thalidomide- and bortezomib-based regimens as first-line treatments having similar OS and PFS. Treatments were considered relatively safe, especially regarding serious AE.

Use of fall risk-increasing drugs in older adults with multiple myeloma: A cross-sectional study.

OBJECTIVE: To investigate the use of fall risk-increasing drugs (FRIDs) and associated factors and to assess the use of medicines that induce neuropathy in older adults with multiple myeloma (MM). METHODS: Cross-sectional study with older adults with MM treated at the outpatient oncology and hematology services in a southeastern Brazilian capital. FRIDs were classified according to the Screening Tool of Older Persons Prescription in older adults with high fall risk (STOPPFall). The high risk of falling was defined using the Medication Fall Risk Score scale, and the medicines that induce neuropathy were identified according to Vilholm et al. (2014) and Jones et al. (2019). Univariate and multivariate analyses were performed to verify the association between variables. RESULTS: Approximately 54.2% of the 153 older adults included in the study were female, and the median age was 70.9 years (IQR = 13; min = 60 and max:92). Around 71.3% used FRIDs, and diuretics (25.6%), antidepressants (20.5%), and opioids (19.9%) were the most used. A total of 32.7% had a high risk of falling. Polypharmacy was associated with a higher risk of using FRIDs. Statins used concomitantly with immunomodulators or bortezomib were the most used neuropathyinducing drugs, increasing fourfold the likelihood of reporting peripheral neuropathy. CONCLUSION: The frequency of use of FRIDs is high in older adults with MM and is positively associated with polypharmacy.

"Real-world" effectiveness of methylphenidate in improving the academic achievement of Attention-Deficit Hyperactivity Disorder diagnosed students-A systematic review.

WHAT IS KNOWN AND OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) symptoms usually impairs academic achievement and can trigger the onset of medication. Methylphenidate is a drug widely prescribed to treat ADHD. However, systematic reviews of randomized clinical trials suggest that it does not lead to great improvements in academic performance. Thus, we aimed to evaluate the evidence on the "real-world" effectiveness of methylphenidate in improving the academic achievement of ADHD students. METHODS: We conducted a systematic review of observational studies retrieved from five electronic databases, besides a manual search and search in grey literature. Studies evaluating treatment with methylphenidate compared to no treatment or other pharmacological/non-pharmacological alternatives used in ADHD were included. The risk of bias of the selected studies was assessed using adapted versions of the Newcastle-Ottawa Scale. RESULTS AND DISCUSSION: Nine studies (from ten reports) were included in the review: four cohorts, two before-and-after designs and three cross-sectional studies. They involved 12,269 children and adolescents aged 6-18 years. The doses of methylphenidate ranged from 10 to 72 mg/day, and the duration of the treatment from 2.6 months to 4.25 years. Five of these studies concluded that methylphenidate improves academic performance. However, three of the four lowest-bias risk studies concluded that the drug is ineffective. Five studies assessed the long-term use of methylphenidate, and four of them concluded that it does not result in better outcomes in the school setting. Most included studies had considerable limitations and significant heterogeneity regarding methodological design and academic performance measurement criteria. WHAT IS NEW AND CONCLUSION: Although some studies indicate that the short-term use of methylphenidate may improve outcomes in the school environment, the available evidence does not support the establishment of adequate conclusions about the real benefits of methylphenidate in the academic improvement of ADHD students.

Use of psychotropic drugs among workers on leave due to mental disorders.

OBJECTIVE: To describe the use of psychotropic drugs among civil servants with registered absenteeism due to mental disorders, and to investigate associations with duration of leave of absence. METHODS: A cross-sectional study with civil servants on leave of absence due to mental disorders, between January and December 2017. Demographic, occupational and clinical variables were extracted from secondary data. Non-parametric tests were used to investigate correlations between use of psychotropic drugs and leave duration. Cluster analysis was used to investigate associations between occupational characteristics and illness profile. RESULTS: Antidepressants were the most commonly used drugs (82.9%). Central tendency values for days on leave differed according to the number of psychotropic drugs used. In cluster analysis, a particular cluster (servants of intermediate age group and work experience - mean of 46 years and 15 years, respectively) stood out regarding use of antidepressants, severity of depression and frequency and duration of leave of absence. CONCLUSION: Leave of absence due to mental disorders was associated with higher rates of psychotropic drug use. The group of servants identified in this study may be a primary target for health promotion, prevention and recovery actions at the organization.

Validation of an Instrument for Measuring Adherence to Treatment With Immunomodulators in Patients With Multiple Myeloma.

Background: Validate the Treatment Adherence Measure (TAM) instrument in outpatients with MM concerning construct validity, reliability and the ceiling and floor effects. Methods: This cross-sectional study included patients diagnosed with MM previously treated with an immunomodulator for at least one month, aged 18 or over, and followed-up in the investigated outpatient clinics. Adherence to immunomodulators was measured by TAM. The TAM's reliability was assessed using Cronbach's alpha; The association between adherence and health-related quality of life was investigated to analyze the divergent and convergent construct, measured by the Quality of Life Questionnaire core (QLQ-C30) and the Quality of Life Questionnaire Multiple Myeloma module (QLQ-MY20). The presence of a ceiling or floor effect in the TAM was also analyzed. Results: Eighty-four patients were included in the study, achieving 97.6% adherence. Cronbach's alpha was 0.41, and the hypothesis of convergent construct validity was confirmed, with statistical significance, in contrast to the hypothesis of divergent construct validity. The presence of the ceiling effect in TAM suggested that this instrument does not allow changes to be detected in individuals concerning adherence to IMiDs. Conclusion: TAM instrument did not show satisfactory validity and reliability to measure MM's adherence. MM patients treated at oncohematological outpatient clinics in a metropolitan region of southeastern Brazil showed high adherence to IMiDs.

Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial. OBJECTIVES: To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults. SEARCH METHODS: In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI. MAIN RESULTS: We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest. AUTHORS' CONCLUSIONS: We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.

Use of psychotropic drugs among workers on leave due to mental disorders / Uso de psicofármacos entre trabalhadores em afastamento laboral por transtornos mentais

ABSTRACT Objective To describe the use of psychotropic drugs among civil servants with registered absenteeism due to mental disorders, and to investigate associations with duration of leave of absence. Methods A cross-sectional study with civil servants on leave of absence due to mental disorders, between January and December 2017. Demographic, occupational and clinical variables were extracted from secondary data. Non-parametric tests were used to investigate correlations between use of psychotropic drugs and leave duration. Cluster analysis was used to investigate associations between occupational characteristics and illness profile. Results Antidepressants were the most commonly used drugs (82.9%). Central tendency values for days on leave differed according to the number of psychotropic drugs used. In cluster analysis, a particular cluster (servants of intermediate age group and work experience - mean of 46 years and 15 years, respectively) stood out regarding use of antidepressants, severity of depression and frequency and duration of leave of absence. Conclusion Leave of absence due to mental disorders was associated with higher rates of psychotropic drug use. The group of servants identified in this study may be a primary target for health promotion, prevention and recovery actions at the organization.

RESUMO Objetivo Descrever a utilização de psicofármacos por servidores públicos com registro de absenteísmo por transtornos mentais, e analisar sua associação com a duração do afastamento do trabalho. Métodos Estudo transversal com servidores públicos em afastamento laboral por transtornos mentais, entre janeiro a dezembro de 2017. Variáveis demográficas, ocupacionais e clínicas foram obtidas a partir de dados secundários. Foram empregados testes não paramétricos para avaliar a correlação entre o uso de psicofármacos e o tempo de afastamento. A análise de cluster foi utilizada para verificar a associação entre as características ocupacionais e o perfil de adoecimento do servidor. Resultados Os antidepressivos foram os medicamentos mais utilizados (82,9%). Observaram-se diferenças nos valores centrais de dias de afastamentos por número de psicofármacos utilizados. Na análise de cluster , um dos conglomerados (servidores com idade e tempo de trabalhos intermediários - média 46 anos de idade e 15 anos de trabalho) destacou-se em relação à utilização de antidepressivos, gravidade do quadro depressivo, frequência e duração do afastamento. Conclusão O afastamento laboral por transtornos mentais esteve associado à maior utilização de psicofármacos. O grupo de servidores identificado pode ser alvo prioritário de ações de promoção, prevenção e recuperação da saúde na instituição.

HIV pre-exposure prophylaxis (PrEP) awareness and acceptability among trans women: a review.

Transgender (trans) women are disproportionally burdened by the HIV epidemic due to complex structural, psychosocial and biological factors. HIV pre-exposure prophylaxis (PrEP) is a biomedical prevention approach for people at substantial risk of acquiring HIV. This literature review assessed awareness, willingness to use, and barriers and facilitators for PrEP acceptability among trans women. A search was conducted through five databases and included studies with primary data and disaggregate results for trans women. Of 255 retrieved citations, 17 met the inclusion criteria and were included. Low to moderate knowledge about PrEP was observed among studies. However, willingness to use PrEP was predominantly high. Frequent barriers to PrEP acceptability included concerns about side effects, cost, hormone therapy, adherence, PrEP-related stigma and interaction with healthcare workers. Facilitators included perceived reduction of HIV risk, fear of HIV/AIDS and reduced dependence on partners. Findings suggest elevated interest in PrEP and highlight important barriers and facilitators that should be specifically addressed to optimize PrEP uptake and use among this highly vulnerable population.

Effectiveness of second-line antiretroviral therapy: the impact of drug switches.

Including antiretroviral drug switches as a measure of ART failure could be more suitable than conventional measures to evaluate health outcomes in "real-world" settings. This is part of a historical cohort of HIV-infected adults who initiated ART from 2001-2005, and were followed up for a maximum of five years in three HIV/AIDS centers in Belo Horizonte, Brazil. Follow-up information included data from 2001-2010. All patients switched from first-line ART were included. Second-line ART effectiveness was measured as the time-to-ART failure. Failure was defined simulating two scenarios: (1) Clinical, immunological and virological failure (scenario 1); and scenario 1 plus ART switches (scenario 2). Descriptive analysis, Kaplan-Meier curves, log-rank test, and Cox proportional hazards model were performed. We identified 119 eligible patients; most had protease inhibitor (PI)-based regimens prescribed as second-line. The incidence of failure was different for the two scenarios (29.4% vs. 54.6% for scenario 1 and 2, respectively; p < 0.001). The main identifiers of failure were increase in viral load (31.1%) for scenario 1 and ART switches (42.8%) for scenario 2. Median duration on second-line ART was 36.8 vs. 19.8 months for scenario 1 and 2, respectively. In the Cox analysis of scenario 2, increased risk was found for patients given PI-based second-line regimens (HR = 2.26; 95% CI: 1.09-3.17). There is a high incidence of ART failure associated with PI-based regimens when ART switches are considered as an indicator of failure. This demonstrates the impact of ART switches in representing lack of ART effectiveness.

Incidence and Predictors of Antiretroviral Treatment Modification in HIV-Infected Adults: A Brazilian Historical Cohort from 2001 to 2010.

This study estimated the incidence of and time to first antiretroviral therapy (ART) modification. This longitudinal analysis comprised a sample of 236 patients from three HIV/AIDS referral centers in Belo Horizonte, Brazil-part of a major historical cohort. Inclusion criteria were as follows: having been treatment-naive patient ≥18 years old who initiated ART between 2001 and 2005 in these three referral centers. The main endpoint was time to first ART modification. Patients were followed up for five years, covering the period 2001-2010, during which time Pearson's chi-square test was performed to compare ART modification between groups. Kaplan-Meier inverse survival curves were employed to describe the probability of ART modification and Cox proportional hazard regression was used to estimate the adjusted hazard ratio (aHR) of ART modification. Among 247 patients from the major cohort, 236 were eligible. Median follow-up time was 37.2 months and the contribution in person-months was 7,615.4 months. A total of 108 (45.8%) patients had their ART regimen modified at least once (incidence rate: 1.42 per 100 person-months). Adverse drug reactions were the main reason for ART modification. Women (aHR = 1.62; p = 0.022) and patients on protease inhibitor- (PI-) based regimens (aHR = 2.70; p < 0.001) were at higher risk of ART modification.

Assessment of primary health care from the perspective of patients hospitalized for ambulatory care sensitive conditions.

BACKGROUND: The hospitalization for ambulatory care sensitive conditions (ACSC) has been used to assess the effectiveness of primary health care (PHC). Due to the existence of different models of organization of PHC in Brazil, it is important to develop indicators and tools for their assessment. OBJECTIVE: Assessment PHC from the perspective of patients hospitalized for ACSC. METHODS: A cross-sectional study was carried out. The patients were interviewed for assessment of PHC quality using the primary care assessment tool and a questionnaire. Descriptive analyses were performed and the Primary Health Care Index (PHCI) was calculated according to the health service modality, either the traditional primary health care (TPHC) or the Family Health Program (FHP). The PHCI of the two health care models were compared. RESULTS: A total of 314 ACSC patients were interviewed 26.4% from the FHP and 73.6% from the TPHC. In general, the PHCI dimension with the lowest score was health service access. There was no significant difference in the general PHCI for the two modalities of services (P = 0.16); however, comprehensiveness was better assessed in the TPHC, while longitudinality, family focus and community orientation were better evaluated by FHP users (P ≤ 0.05). CONCLUSION: The FHP was found to be better qualified to establish longitudinality in the community, an important dimension for continued care. However, promoting access to and consolidating a proactive care model focussed on family shows to be a great challenge for the implementation of a quality and resolutive PHC in large urban centres.

Availability of data on adverse reactions to antiretroviral drugs in medical charts according to the Naranjo algorithm: an example of a Brazilian historical cohort.

BACKGROUND AND OBJECTIVE: Although not designed for research purposes, medical charts can be a unique source for obtaining information on long-term adverse drug reactions. This study aimed to assess the availability of key information on paper-based patient medical records needed to detect long-term adverse reactions to antiretroviral therapy (ART). METHODS: This is an ongoing historical cohort study carried out in three public HIV/AIDS referral centers in Belo Horizonte, Brazil. Medical charts of treatment-naïve HIV-infected adult patients initiating ART between 2001 and 2005 were reviewed for a follow-up period of up to 5 years after the first ART prescription. Descriptive analysis was performed by estimating the absolute and relative frequencies of selected variables. The Naranjo algorithm was employed to assess the availability of data on long-term adverse outcomes in medical charts. RESULTS: A total of 233 medical charts were eligible for study and 26.1% contained at least one long-term adverse reaction, corresponding to 45 cases of dyslipidemia (19.3%), 16 (6.9%) of lipodystrophy and 5 of type 2 diabetes mellitus (2.1%). Temporal relationship and ART switch could be better documented from medical charts. Information on reasons for ART switching and alternative causes for adverse reactions was very lacking. CONCLUSIONS: Specific tools should be developed and included in medical routines to improve adverse reaction reporting by physicians and other health professionals. This could be implemented simultaneously with the transition from paper to electronic medical charts in Brazil, facilitating the identification of long-term adverse reactions to antiretroviral drugs in epidemiological studies and in clinical practice.

Lipodystrophy among patients with HIV infection on antiretroviral therapy: a systematic review protocol.

INTRODUCTION: Lipodystrophy is a frequent and disfiguring adverse effect of antiretroviral therapy (ART) in patients with HIV. It affects the quality of life of the patient and adherence to treatment, and generates new needs for comprehensive healthcare services. The aim of this study will be to conduct a systematic review of the literature from observational studies and describe lipodystrophy among patients with HIV infection during current or previous use of ART. METHODS AND ANALYSIS: A systematic review of observational studies published in MEDLINE, CINAHL, LILACS, EMBASE and International Pharmaceutical Abstracts will be carried out. Citations of included studies will be checked to identify additional studies not identified in the electronic searches. It will include any observational study that considered lipodystrophy as the primary or secondary outcome and that had enrolled adolescent and adult patients with HIV infection who were on current or previous ART for at least 6 months. Data extraction and analysis will be performed independently by two reviewers. The extracted data will be discussed, decisions documented and, where necessary, the authors of the studies will be contacted for clarification. Measures of frequency, prevalence and incidence of lipodystrophy will be stratified according to definition, method of diagnosis and risk factors of the outcome. ETHICS AND DISSEMINATION: Ethics is not required given this is a protocol for a systematic review. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. Updates of the review will be conducted to inform and guide healthcare practice. PROTOCOL REGISTRATION: PROSPERO-42013005450.

Allergic contact dermatitis due to beta-blockers in eye drops: a retrospective analysis of multicentre surveillance data 1993-2004.

Topically applied ophthalmic drugs are a potential cause of allergic contact dermatitis of the periorbital region. The objectives of this study were to assess the frequency and spectrum of contact allergy to topically applied beta-blocker containing eye drops. Data of the Information Network of Departments of Dermatology (IVDK) collected between 1993 and 2004 was analysed. Out of 112,430 patch-tested patients, 332 had been tested with their own topical anti-glaucoma eye drops containing different beta-blockers because of suspected allergic contact dermatitis. The frequency of positive test reactions was related to exposure intensity, as estimated by annual prescription rates in Germany. A total of 43/332 (12.95%) showed at least one positive patch test reaction. Positive reactions were observed to products containing timolol (n = 21), metipranolol (n = 13) and levobunolol (n = 11) without conceivable cross-reactivity. Whereas exposure to beta-blocker-containing eye drops remained stable over the years, as estimated by the prescription rates, a slight, non-significant increase in positive patch-reactions to these substances was noted. This is the first systematic analysis of a large set of data on patients' own beta-blocker topical medications, the results indicating that contact allergy should be considered as important, if rare, adverse event caused by this family of drugs.