Pain in people seeking and receiving opioid agonist treatment: A systematic review and meta-analysis of prevalence and correlates.

BACKGROUND AND AIMS: People with opioid use disorder (OUD) commonly experience pain including chronic pain. Despite the high prevalence, few studies have systematically examined the prevalence and correlates of pain among people seeking or receiving opioid agonist treatment (OAT) for OUD. This review aimed to determine the prevalence of pain in this population globally, and estimate the association between chronic pain and other demographic and clinical characteristics. METHODS: Electronic searches were conducted in three databases (Medline, Embase and PsycINFO) from the inception until October 2022. Eligible studies reported prevalence rates of current and/or chronic pain. Meta-analyses examining the main prevalence estimates were conducted by Stata SE 18.0, and comorbid clinical conditions were analysed by Review Manager 5.4. RESULTS: Fifty-six studies (n participants = 35 267) from sixty-seven publications were included. Prevalence estimates of current and chronic pain were reported in 27 (48.2%) and 40 studies (71.4%), respectively. Most studies were conducted in North America (71.4%, n = 40) and used cross-sectional designs (64.3%, n = 36). Meta-analyses revealed a pooled prevalence of 60.0% (95% confidence interval [CI]: 52.0-68.0) for current pain and 44.0% [95% CI: 40.0-49.0] for chronic pain. Chronic pain was positively associated with older age (mean deviation of mean age: 2.39 years, 95% CI: 1.40-3.37; I2 = 43%), unemployment (odds ratio [OR] = 0.57, 95% CI: 0.42-0.76; I2 = 78%), more severe mental health symptoms (e.g. more severe depression (standardised mean difference [SMD] of mean scores: 0.45, 95% CI: 0.20-0.70; I2 = 48%) and anxiety symptoms (SMD: 0.52, 95% CI: 0.17-0.88; I2 = 67%), and hepatitis C (OR = 1.41, 95% CI: 1.03-1.94; I2 = 0%). No association was observed between chronic pain and the onset and type of OAT, geographic location, study design, survey year, participant age or use of specific pain assessment tools. CONCLUSIONS: There appears to be a high prevalence of pain among people seeking or receiving opioid agonist treatment for opioid use disorder compared with the general population, with positive associations for older age, unemployment, hepatitis C and the severity of some mental health symptoms.

Comparison of Neurovascular Structures at Risk During Ankle Arthroscopy: A Cadaveric Study.

BACKGROUND: Arthroscopy has become increasingly common for diagnosis and treatment of ankle joint pathology. The four most common portals used for ankle arthroscopy are the anteromedial, anterolateral, posteromedial, and posterolateral. Anatomy of neurovascular structures along the ankle can significantly vary. METHODS: The distance of neurovascular structures was compared with anatomical landmarks of ankle arthroscopic portals to verify safe zones for scope insertion. Twenty-six fresh frozen cadavers were used, with dissection of standard anatomical landmarks and neurovascular structures. Portals were made and verified with a 2.7-mm arthroscope. RESULTS: Significant differences were found in mean distances between anatomical landmarks except for the peroneus tertius tendon to the intermediate dorsal cutaneous nerve (P = .181; all others, P < .0001). In quantifying a scope space, the anteromedial and anterolateral portals had the largest margin of error at 0.82 cm and 1.04 cm, respectively. The saphenous nerve and vein were an average of 1.39 cm and 1.23 cm, respectively, from the anteromedial portal. The peroneus tertius tendon was an average of 0.23 cm from the intermediate dorsal cutaneous nerve. The tibialis anterior tendon was an average of 1.10 cm lateral to the medial gutter; the peroneus tertius tendon, 1.31 cm medial to the lateral gutter; and the Achilles tendon, 0.94 and 0.73 cm from the medial and lateral gutters, respectively. CONCLUSIONS: Among common ankle arthroscopic approaches, the anterolateral portal features the highest anatomic variability. These data support the standard protocol of beginning with the anteromedial portal to facilitate visualization of lateral-sided anatomy before anterolateral portal placement.

Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE): protocol for a helix-counterbalanced randomised controlled trial.

INTRODUCTION: Clinical practice guidelines recommend against the routine use of psychotropic medications in residential aged care facilities (RACFs). Knowledge brokers are individuals or groups who facilitate the transfer of knowledge into practice. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of using knowledge brokers to translate Australia's new Clinical Practice Guidelines for the Appropriate Use of Psychotropic Medications in People Living with Dementia and in Residential Aged Care. METHODS AND ANALYSIS: The Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE) trial is a helix-counterbalanced randomised controlled trial. The 12-month trial will be conducted in up to 19 RACFs operated by four Australian aged care provider organisations in Victoria, New South Wales, Western Australia and Queensland. RACFs will be randomised to receive three levels of implementation strategies (knowledge broker service, pharmacist-led quality use of medications education activities and distribution of the Guidelines and supporting materials) across three medication contexts (antipsychotics, benzodiazepines and antidepressants). Implementation strategies will be delivered by an embedded on-site aged care pharmacist working at a system level across each participating RACF. All RACFs will receive all implementation strategies simultaneously but for different medication contexts. The primary outcome will be a composite dichotomous measure of 6-month RACF-level concordance with Guideline recommendations and good practice statements among people using antipsychotics, benzodiazepines and antidepressants for changed behaviours. Secondary outcomes will include proportion of residents with Guideline concordant use of antipsychotics, benzodiazepines and antidepressants measured at the RACF-level and proportion of residents with psychotropic medication use, hospitalisation, falls, falls with injury, polypharmacy, quality of life, activities of daily living, medication incidents and behavioural incidents measured at the RACF-level. DISCUSSION: The EMBRACE trial investigates a novel guideline implementation strategy to improve the safe and effective use of psychotropic medications in RACFs. We anticipate that the findings will provide new information on the potential role of knowledge brokers for successful and cost-effective guideline implementation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623001141639. Registered 6 November 2023 - retrospectively registered, https://www.anzctr.org.au/TrialSearch.aspx .

Trajectories of prescription opioid tapering in patients with chronic non-cancer pain: a retrospective cohort study, 2015-2020.

OBJECTIVE: To identify common opioid tapering trajectories among patients commencing opioid taper from long-term opioid therapy for chronic non-cancer pain and to examine patient-level characteristics associated with these different trajectories. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: Patients prescribed opioid analgesics between 2015 and 2020. METHODS: Group-based trajectory modeling and multinomial logistic regression analysis were conducted to determine tapering trajectories and to examine demographic and clinical factors associated with the different trajectories. RESULTS: A total of 3369 patients commenced a taper from long-term opioid therapy. Six distinct opioid tapering trajectories were identified: low dose / completed taper (12.9%), medium dose / faster taper (12.2%), medium dose / gradual taper (6.5%), low dose / noncompleted taper (21.3%), medium dose / noncompleted taper (30.4%), and high dose / noncompleted taper (16.7%). A completed tapering trajectory from a high opioid dose was not identified. Among patients prescribed medium opioid doses, those who completed their taper were more likely to have higher geographically derived socioeconomic status (relative risk ratio [RRR], 1.067; 95% confidence interval [CI], 1.001-1.137) and less likely to have sleep disorders (RRR, 0.661; 95% CI, 0.463-0.945) than were those who didn't complete their taper. Patients who didn't complete their taper were more likely to be prescribed strong opioids (eg, morphine, oxycodone), regardless of whether they were tapered from low (RRR, 1.444; 95% CI, 1.138-1.831) or high (RRR, 1.344; 95% CI, 1.027-1.760) doses. CONCLUSIONS: Those prescribed strong opioids and high doses appear to be less likely to complete tapering. Further studies are needed to evaluate the clinical outcomes associated with the identified trajectories.

Opioid characteristics and nonopioid interventions associated with successful opioid taper in patients with chronic noncancer pain.

ABSTRACT: Current research indicates that tapering opioids may improve pain and function in patients with chronic noncancer pain. However, gaps in the literature remain regarding the choice of opioid and nonopioid interventions to support a successful taper. This study used an Australian primary care data set to identify a cohort of patients on long-term opioid therapy commencing opioid taper between January 2016 and September 2019. Using logistic regression analysis, we compared key clinical factors associated with differing taper outcomes. Of a total of 3371 patients who commenced taper, 1068 (31.7%) completed taper within 12 months. In the 3 months after commencement of taper, compared with those who did not complete taper, patients who successfully completed opioid taper were less likely to be prescribed buprenorphine (odds ratio [OR] 0.691; 95% CI: 0.530-0.901), fentanyl (OR, 0.429; 95% CI: 0.295-0.622), and long-acting (LA) opioids, including methadone (OR, 0.349; 95% CI: 0.157-0.774), oxycodone-naloxone (OR, 0.521; 95% CI: 0.407-0.669), and LA tapentadol (OR, 0.645; 95% CI: 0.461-0.902), but more likely to be prescribed codeine (OR, 1.308; 95% CI: 1.036-1.652). Compared with those who did not complete taper, patients who successfully tapered were less likely to be prescribed any formulations of oxycodone (short-acting [SA]: OR, 0.533; 95% CI: 0.422-0.672, LA: OR, 0.356; 95% CI: 0.240-0.530) and tramadol (SA: OR, 0.370; 95% CI: 0.218-0.628, LA: OR, 0.317; 95% CI: 0.234-0.428). The type of opioid prescribed in the months after commencement of taper seems to influence the taper outcomes. These findings may inform prospective studies on opioid taper.

Identifying Prescription-Opioid-Related Risks Using Prescription Drug Monitoring Programs' Algorithms and Clinical Screening Tools.

BACKGROUND: Pharmacists adopt various approaches to identifying prescription-opioid-related risks and harms, including prescription drug monitoring programs (PDMPs) and clinical screening tools. This study aims to compare 'at-risk' patients according to the published Australian PDMP algorithms with the validated Routine Opioid Outcome Monitoring (ROOM) clinical screening tool. METHODS: Data were used from an implementation study amongst people who had been prescribed regular opioids. We examined the results from ROOM and the patients' dispensing history over the previous 90 days. A chi-squared test was used to examine the association between risk according to (i) a PDMP alert and a clinical risk per ROOM; (ii) a PDMP alert and positive screening for opioid use disorder; and (iii) a PDMP 'high-dose' alert (average of >100 mg OME/day in the past 90 days) and any ROOM-validated risk. RESULTS: No significant associations were found between being 'at-risk' according to any of the PDMP alerts and clinical risk as identified via the ROOM tool (x2 = 0.094, p = 0.759). There was only minimal overlap between those identified as 'at-risk' via PDMP alerts and those meeting the clinical risk indicators; most patients who were 'at-risk' of clinical opioid-related risk factors were not identified as 'at-risk' based on PDMP alerts. CONCLUSIONS: PDMP alerts were not predictive of clinical risk (as per the ROOM tool), as many people with well-established clinical risks would not receive a PDMP alert. Pharmacists should be aware that PDMPs are limited to identifying medication-related risks which are derived using algorithms; therefore, augmenting PDMP information with clinical screening tools can help create a more detailed narrative of patients' opioid-related risks.

Cohort profile: Using primary care data to understand Opioid Prescribing, Policy Impacts and Clinical Outcomes (OPPICO) in Victoria, Australia.

PURPOSE: The OPPICO cohort is a population-based cohort based on non-identifiable electronic health records routinely collected from 464 general practices in Victoria, Australia, created with the aim of understanding opioid prescribing, policy impacts and clinical outcomes. The aim of this paper is to provide a profile of the study cohort by summarising available demographic, clinical and prescribing characteristics. PARTICIPANTS: The cohort described in this paper comprises people who were aged at least 14 years at cohort entry, and who were prescribed an opioid analgesic at least once at participating practices for a total of 1 137 728 person-years from 1 January 2015 to 31 December 2020. The cohort was formed using the data collected from electronic health records through the Population Level Analysis and Reporting (POLAR) system. The POLAR data primarily consist of patient demographics, clinical measurements, Australian Medicare Benefits Scheme item numbers, diagnoses, pathology testing and prescribed medications. FINDING TO DATE: In total, the cohort consists of 676 970 participants with 4 389 185 opioid prescription records from 1 January 2015 to 31 December 2020. Approximately half (48.7%) received a single opioid prescription, and 0.9% received more than 100 opioid prescriptions. The mean number of opioid prescriptions per patient was 6.5 (SD=20.9); prescriptions for strong opioids accounted for 55.6% of all opioid prescriptions. FUTURE PLANS: The OPPICO cohort data will be used for various types of pharmacoepidemiological research, including examining the impact of policy changes on coprescription of opioids with benzodiazepines and gabapentin, and monitoring trends and patterns of other medication utilisation. Through data-linkage between our OPPICO cohort and hospital outcome data, we will examine whether policy changes for opioid prescribing lead to changes in prescription opioid-related harms, and other drug and mental health-related outcomes. TRIAL REGISTRATION NUMBER: EU PAS Register (EUPAS43218, prospectively registered).

What are the research priorities for optimising the safe and effective use of opioids in Australian general practice?

INTRODUCTION: Persistent high rates of prescription opioid use and harms remain a concern in Australia, Europe and North America. Research priority setting can inform the research agenda, strategic responses and evidence-based interventions. The objective of this study was to establish research priorities related to the safe and effective use of prescription opioids in general practice. METHODS: Consumers, clinicians and policy makers were invited to participate in a structured consensus workshop in May 2021. A modified nominal group technique was used to explore research priorities for the safe and effective use of opioids in Australian general practice. Research priorities were identified, consolidated and prioritised using a structured process. RESULTS: Seventeen consumer, medical, pharmacy, nursing, allied health and policy participants generated 26 consolidated priorities across three domains: (i) consumer-focused priorities; (ii) clinician and practice-focused priorities; and (iii) system and policy-focused priorities. The highest ranked research priorities in each of the domains were consumer characteristics that influence opioid prescribing and outcomes, opioid deprescribing strategies, and system-level barriers to prescribing alternatives to opioids, in the consumer, clinician and practice, and system and policy domains, respectively. DISCUSSION AND CONCLUSION: The priorities reflect opportunities for research priority setting within Australian general practice. The priorities provide a map for future qualitative and quantitative research that will inform safe and effective opioid prescribing.

COVID-19 restrictions and the incidence and prevalence of prescription opioid use in Australia - a nationwide study.

The COVID-19 pandemic has disrupted seeking and delivery of healthcare. Different Australian jurisdictions implemented different COVID-19 restrictions. We used Australian national pharmacy dispensing data to conduct interrupted time series analyses to examine the incidence and prevalence of opioid dispensing in different jurisdictions. Following nationwide COVID-19 restrictions, the incidence dropped by -0.40 (95% confidence interval [CI]: -0.50, -0.31), -0.33 (95% CI: -0.46, -0.21) and -0.21 (95% CI: -0.37, -0.04) per 1000 people per week and the prevalence dropped by -0.85 (95% CI: -1.39, -0.31), -0.54 (95% CI: -1.01, -0.07) and -0.62 (95% CI: -0.99, -0.25) per 1000 people per week in Victoria, New South Wales and other jurisdictions, respectively. Incidence and prevalence increased by 0.29 (95% CI: 0.13, 0.44) and 0.72 (95% CI: 0.11, 1.33) per 1000 people per week, respectively in Victoria post-lockdown; no significant changes were observed in other jurisdictions. No significant changes were observed in the initiation of long-term opioid use in any jurisdictions. More stringent restrictions coincided with more pronounced reductions in overall opioid initiation, but initiation of long-term opioid use did not change.

Using primary care data to understand opioid prescribing, policy impacts and clinical outcomes: A protocol for the OPPICO study.

INTRODUCTION: Prescription opioid use in Australia has increased over the last 3 decades. The majority of opioids are prescribed and dispensed in primary care, however, there are few studies that are specific to opioid prescribing in this setting. Evidence about the impact of key government policy strategies to optimize opioid prescribing in primary care is limited. The aim of this study is to examine the impact of recent policy changes and clinical guidelines on opioid prescribing in primary care. METHODS AND ANALYSIS: Longitudinal analysis of people prescribed opioid analgesics using Population Level Analysis and Reporting (POLAR) data. POLAR is a primary care dataset comprising 464 primary health care practices in Victoria, Australia. People prescribed opioid analgesics between 2015 and 2020 will be included. The impact of opioid policies and guideline recommendations will be evaluated using interrupted time series models. Group- based trajectory modelling and multivariate regression will be used to identify patterns of opioid cessation and the provision of corresponding non-opioid interventions. ETHICS AND DISSEMINATION: The study has received Monash University Human Research Ethics Committee approval (ID 24139). Permission to access, collate and use POLAR data is granted from Outcome Health as the data custodians. The results of this study will be disseminated through publication in international journals, presented at national and international scientific conferences, and disseminated to consumers, policy makers, primary care providers and primary health networks. PROTOCOL REGISTRATION DETAILS: EU PAS Register (EUPAS43218).

Opioid prescribing in the emergency department of a tertiary hospital: A retrospective audit of hospital discharge data.

OBJECTIVE: EDs are a common source of prescription opioids on discharge. We explored opioid prescribing practices in an ED at a tertiary hospital in Victoria, Australia. METHODS: A retrospective audit over a 6 month period of patients discharged from the ED to the community with the maximum allowable quantities of prescription opioids. RESULTS: There was a total of 3301 patient-episodes discharged with a prescription from the ED. Of these, 766 (23.2%, 95% confidence interval [CI] 21.8-24.6) were prescribed opioids, with over half discharged with the maximum allowable quantities of prescription opioids. Immediate-release opioids were prescribed in 362 (85.8%, 95% CI 82.5-89.1) patient-episodes, a combination of immediate-release and slow-release preparations were prescribed in 29 (6.9%, 95% CI 4.5-9.3) and 31 (7.3%, 95% CI 4.8-9.8) were prescribed as slow-release opioids alone. Co-prescription of other analgesia with opioids occurred in 152 (36.0%, 95% CI 31.4-40.6) patient-episodes. Possible drug interactions between opioids and other medications were noted in 117 (27.7%, 95% CI 23.4-32.0) patient-episodes. Discharge summaries were prepared for 360 (85.3%, 95% CI 81.9-88.7) patient-episodes, but only 171 (40.5%, 95% CI 35.8-45.2) included a plan to address the opioids, be that an opioid-weaning regimen, analgesia review or referral to a pain specialist on discharge. CONCLUSION: Opioid prescribing was common in this ED, with almost one-quarter of discharge prescriptions being for a prescription opioid. This audit highlights potential areas for practice improvement including review of the quantity of opioid tablets prescribed as well as an opioid plan on discharge from the ED.

Short-term use of telmisartan attenuates oxidation and improves Prdx2 expression more than antioxidant ß-blockers in the cardiovascular systems of spontaneously hypertensive rats.

Reactive oxygen species (ROS) and antioxidant enzymes are required to maintain homeostasis. The loss of this balance can cause excessive ROS production and damage to the cardiovascular tissues. Angiotensin II receptor blockers (ARBs) and ß-blockers with antioxidant effects may inhibit ROS in the cardiovascular system. In this study, we directly compared the effects of ARBs and ß-blockers with antioxidant properties on cardiovascular protection and the regulation of endothelial progenitor cell (EPC) numbers in the setting of oxidative stress in hypertensive rats. To compare the effects of the drugs, animals were divided into the following groups: Wistar-Kyoto rats (WKY), untreated spontaneously hypertensive rats (SHR) and SHR treated with tempol (TEMP, 5 mg kg(-1) per day), trichlorothiazide (TCTZ, 1.6 mg kg(-1) per day), atenolol (25 mg kg(-1) per day), nebivolol (NEBL, 5 mg kg(-1) per day), carvedilol (CVDL, 30 mg kg(-1) per day) or telmisartan (TERT, 5 mg kg(-1) per day). Following 2 weeks of treatment, blood pressures (BPs) and aortic wall thicknesses were similarly reduced in each antihypertensive drug-treated group. Superoxide anion and malondialdehyde levels were significantly reduced following treatment with NEBL, CVDL and TERT. Additionally, the expression levels of NADPH oxidase subunits were also reduced in the TERT-, CVDL- and NEBL-treated groups. Furthermore, these drugs improved both EPC numbers and the expression levels of peroxiredoxin 2 (Prdx2), an antioxidant enzyme, in the heart and kidneys but not the aorta. Cardiac Prdx2 expression, in particular, was markedly improved by TERT, NEBL and CVDL treatment, and renal Prdx2 expression was enhanced by TEMP. Our data indicate that short-term treatment with TERT may have more beneficial effects on cardiovascular protection, EPC number improvements and Prdx2 expression compared with CVDL and NEBL. In conclusion, TERT may positively modulate the balance between oxidative stress and antioxidant properties and demonstrate capabilities beyond its BP-lowering effects.

The effect of vitronectin on the differentiation of embryonic stem cells in a 3D culture system.

While stem cell niches in vivo are complex three-dimensional (3D) microenvironments, the relationship between the dimensionality of the niche to its function is unknown. We have created a 3D microenvironment through electrospinning to study the impact of geometry and different extracellular proteins on the development of cardiac progenitor cells (Flk-1(+)) from resident stem cells and their differentiation into functional cardiovascular cells. We have investigated the effect of collagen IV, fibronectin, laminin and vitronectin on the adhesion and proliferation of murine ES cells as well as the effects of these proteins on the number of Flk-1(+) cells cultured in 2D conditions compared to 3D system in a feeder free condition. We found that the number of Flk-1(+) cells was significantly higher in 3D scaffolds coated with laminin or vitronectin compared to colIV-coated scaffolds. Our results show the importance of defined culture systems in vitro for studying the guided differentiation of pluripotent embryonic stem cells in the field of cardiovascular tissue engineering and regenerative medicine.

Diagnóstico da Síndrome de Turner: a experiência do Instituto Estadual de Diabetes e Endocrinologia - Rio de Janeiro, de 1970 a 2008 / Diagnosis of Turner's Syndrome: the experience of the Rio de Janeiro State Institute of Diabetes and Endocrinology between 1970 and 2008

OBJETIVOS: descrever a experiência no diagnóstico da Síndrome de Turner (ST), focalizando a distribuição dos cromossomos, a idade, os sinais e sintomas característicos, conforme as fases da vida (lactância, infância, adolescência e adulta). MÉTODOS: estudo descritivo com 178 pacientes, atendidos de 1970 até 2008. Para análise estatística das diferenças percentuais usou-se o Epi-Info-2000 e para as diferenças entre as médias de idades o teste t de Student e o ANOVA. RESULTADOS: os cariótipos encontrados foram: 79 com 45,X (35,4 por cento), 36 com isocromossomo Xq (20,2 por cento) e 63 com outros mosaicos (35,4 por cento). A média de idade do diagnóstico foi de 12,6 anos, sendo menor naquelas com 45,X. Tiveram o diagnóstico feito na lactância 11,3 por cento das pacientes, 25,3 por cento na infância, 51,1 por cento na adolescência e 12,4 por cento na fase adulta. Daquelas diagnosticadas antes dos cinco anos de idade, 70,6 por cento apresentaram 45,X. Os sinais que levaram à suspeita diagnóstica na lactância foram o pescoço alado e o linfedema congênito de pés/mãos associados às dismorfias típicas; na infância e adolescência foi a baixa estatura. Cubitus valgus foi encontrado em 72,5 por cento das pacientes e orelhas anômalas em 65 por cento das pacientes diagnosticadas com menos de um ano de idade. CONCLUSÃO: o diagnóstico da ST é desnecessariamente atrasado, levando-se em consideração que algumas características típicas podem já estar presentes desde o nascimento.

OBJECTIVES: to describe the Rio de Janeiro State Institute of Diabetes and Endocrinology's experience in diagnosing Turner Syndrome (TS), focusing on the distribution of chromosomes, age, and typical signs and symptoms, according to life stage (breast feeding, childhood, adolescence and adulthood). METHODS: a descriptive study was conducted of 178 patients, attending the Institute between 1970 and 2008 for the purposes of statistical analysis of the percentage differences using Epi-Info-2000 and of the differences between the mean ages using Student's t test and ANOVA Results: the caryotypes found were: 79 with 45,X (35.4 percent), 36 with isochromosome Xq (20.2 percent) and 63 with other mosaics (35.4 percent). The mean age on diagnosis was 12.6 years, this figure being lower in patients with 45,X. The syndrome was diagnosed during breast feeding in 11.3 percent of patients, during childhood in 25.3 percent, during adolescence in 51.1 percent, and in 12.4 percent in adulthood. In those diagnosed before the age of five years, 70,6 percent had 45,X, signs that led to a suspected diagnosis during breast feeding were a webbed neck and congenital lymphedema in the hands and feet associated with typical dysmorphias. In childhood and adolescence the sign was short stature. Cubitus valgus was found in 72.5 percent of patients and abnormal ears in 65 percent of those diagnosed at an age of less than one year. CONCLUSION: diagnosis of TS does not necessarily have to be late, as some typical characteristics may already be present at birth.

Discursos médicos em construção: um estudo com residentes em Obstetrícia/Ginecologia do Instituto Fernandes Figueira/Fiocruz / Construction of medical discourse: an institutional case study with Obstetrics/Gynecology residents at the Fernandes Figueira Institute, Oswaldo Cruz Foundation

Este estudo discute a construção do discurso especializado, a partir do verbalizado por médicos após dois anos de residência médica em Obstetrícia/Ginecologia no Instituto Fernandes Figueira, Fundação Oswaldo Cruz. A pesquisa foi operacionalizada em duas etapas: observação participante de reuniões clínicas da Obstetrícia e da Ginecologia e construção de fontes orais. Foi realizada análise semiótica das notas de campo e do material transcrito das entrevistas. Os resultados giram em torno de dois eixos: a caracterização do perfil do médico obstetra/ginecologista e a convivência com o normal e o estranho no contato com as pacientes, como integrantes da construção do discurso especializado, no ambiente escolhido para a pesquisa. Conclui-se que a residência conduz ao discurso especializado, escudado, principalmente, na utilização de exames complementares, como os que fornecem imagens, visto que tais exames são percebidos como revelando objetivamente o corpo real. Tal fato infunde segurança nos residentes, mas, por outro lado, afasta-os da atenção à escuta da história da paciente e da composição da narrativa médica, fragmentando o processo de exercício da semiologia clínica.

This study discusses the construction of a specialized discourse, based on the experience of Ob-Gyn medical residents at the Fernandes Figueira Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. The research consisted of two steps: participant observation in Obstetrics and Gynecology meetings, and the construction of oral sources. The methodology included a semiotic analysis of field notes and interviews. The results focus on two key aspects: characterization of the profile of obstetricians/gynecologists and contact with normalcy and strangeness with patients, as part of the construction of the specialized discourse within the setting chosen for the research. The study concludes that Ob-Gyn residency leads to a specialized discourse, backed mainly by the use of complementary tests such as imaging, since such tests are perceived as objectively revealing the real body. This fact gives residents confidence, but it can also distract them from listening to the patient's history and constructing the clinical narrative, thus fragmenting the exercise of clinical semiology.

[Revisiting establishments of the etiology of Turner syndrome]. / Revisitando o desvendamento da etiologia da síndrome de Turner.

Based on an interview with José Carlos Cabral de Almeida, who took part in the investigative process, the article explores the research that culminated in the establishment of the genetic etiology of Turner syndrome. Cabral de Almeida also discusses other work that he sees as landmarks in the birth of cytogenetics and offers his current view of the development of clinicalgenetics and the important role played by cytogenetics, which affords more precise means of diagnosis, prognosis, and control ofgenetic disorders. In its conclusion, the article points to pioneer work that continues to impact medical genetics, especially the study of human chromosomes, still fundamental to the success of linking human genetics and disease processes.

Doença de Hirschsprung: experiência com uma série de 55 casos / Hirschsprung's disease: experiment with a serie of 55 cases

OBJETIVOS: analisar aspectos clínicos de pacientes com Doença de Hirschprung (DH). MÉTODOS: realizou-se estudo de caso institucional, retrospectivo, via revisão de prontuários de pacientes com DH atendidos no Instituto Fernandes Figueira entre 1993 e 2003. RESULTADOS: Em um total de 55 pacientes, 98 por cento apresentaram sintomas neonatais, sendo 47,2 por cento diagnosticados nesse período; em 88,9 por cento o enema baritado foi conclusivo; 69 por cento tinham DH de segmento curto; 16,3 por cento síndrome de Down; 15,2 por cento outras anomalias congênitas; 40 por cento foram rastreados para mutações RET associadas a neoplasias endócrinas múltiplas (MEN2A), não sendo detectada nenhuma; 63,6 por cento fizeram abaixamento estagiado do colon/íleo; 12,72 por cento abaixamento endoretal transanal primário; as principais complicações cirúrgicas foram sepse, enterocolite e obstrução intestinal; distúrbios da defecação foram detectados anos pós-cirurgia; a taxa de letalidade foi 9,25 por cento; os óbitos relacionaram-se a enterocolite e sepse pós-operatórias. CONCLUSÃO: embora apresentasse sintomas neonatais, a maioria dos pacientes foi diagnosticada tardiamente. Enterocolite foi a principal causa de morbimortalidade. Distúrbios da defecação ocorrem com frequência, demandando follow-up prolongado. Embora rara, a associação com MEN2A precisa ser investigada devido à agressividade da doença. A heterogeneidade clínica e genética da DH exige atuação de equipe multidisciplinar.

OBJECTIVES: to analyze clinical features of patients with Hirschprung's Disease (HD). METHODS: a retrospective institutional case study was carried out using the medical records of patients with HD attending the Fernandes Figueira Institute between 1993 and 2003. RESULTS: out of a total of 55 patients, 98 percent presented symptoms on birth, 47.2 percent of whom were diagnosed during the neonatal period; in 88.9 percent of cases the barium enema was conclusive; 69 percent had short segment HD; 16.3 percent Down's Syndrome; 15.2 percent other congenital anomalies; 40 percent were screened for RET mutations associated with multiple endocrine neoplasias (MEN2A), although none were detected; 63.6 percent had staged pull-through surgery on the colon or ileum; 12.72 percent primary transanal endorectal pull-through surgery; the main complications arising from surgery were sepsis, enterocolitis and obstruction of the intestines; abnormal bowel movements were detected years after the surgery; the mortality rate was 9.25 percent, the causes of death being post-operal enterocolitis and sepsis. CONCLUSION: although patients presented symptoms on birth, most were diagnosed at a later stage. Enterocolitis was the main cause of death. Abnormal bowel movements frequently occurred, requiring prolonged follow-up. Although rare, the association with MEN2A needs to be investigated owing to the highly aggressive nature of the disease. The clinical and genetic heterogeneity of HD necessitates the involvement of a multidisciplinary team.

Revisitando o desvendamento da etiologia da síndrome de Turner / Revisiting establishment of the etiology of Turner syndrome

Com base em entrevista com José Carlos Cabral de Almeida, o artigo aborda a investigação que culminou no estabelecimento da etiologia genética da síndrome de Turner. Além de discutir especificamente esse processo, do qual fez parte, o entrevistado discorre sobre outros trabalhos que, em sua avaliação, marcaram as origens da citogenética. O artigo apresenta ainda a visão atual de Cabral sobre o desenvolvimento da genética clínica e a importância da citogenética em prover meios mais precisos de diagnose, prognóstico e controle das doenças genéticas. A conclusão aponta os trabalhos referidos como pioneiros e, até hoje, relevantes para a genética médica, especialmente no estudo dos cromossomos humanos, aspecto ainda fundamental para o sucesso da correlação de genética humana e processos de adoecimento.

Based on an interview with José Carlos Cabral de Almeida, who took part in the investigative process, the article explores the research that culminated in the establishment of the genetic etiology of Turner syndrome. Cabral de Almeida also discusses other work that he sees as landmarks in the birth of cytogenetics and offers his current view of the development of clinical genetics and the important role played by cytogenetics, which affords more precise means of diagnosis, prognosis, and control of genetic disorders. In its conclusion, the article points to pioneer work that continues to impact medical genetics, especially the study of human chromosomes, still fundamental to the success of linking human genetics and disease processes.

Revisitando o desvendamento da etiologia da síndrome de Turner / Revisiting establishment of the etiology of Turner syndrome

Com base em entrevista com José Carlos Cabral de Almeida, o artigo aborda a investigação que culminou no estabelecimento da etiologia genética da síndrome de Turner. Além de discutir especificamente esse processo, do qual fez parte, o entrevistado discorre sobre outros trabalhos que, em sua avaliação, marcaram as origens da citogenética. O artigo apresenta ainda a visão atual de Cabral sobre o desenvolvimento da genética clínica e a importância da citogenética em prover meios mais precisos de diagnose, prognóstico e controle das doenças genéticas. A conclusão aponta os trabalhos referidos como pioneiros e, até hoje, relevantes para a genética médica, especialmente no estudo dos cromossomos humanos, aspecto ainda fundamental para o sucesso da correlação de genética humana e processos de adoecimento.(AU)

Perfil clínico de 62 casos de distúrbios da diferenciação sexual / Clinical profile of 62 cases of sexual differentiation disorders

Objetivo: Descrever o perfil clínico dos casos de distúrbios da diferenciação sexual em acompanhamento no Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, no Rio de Janeiro, nos últimos cinco anos.Métodos: Revisão dos prontuários dos pacientes, com o diagnóstico de genitália ambígua em acompanhamento nos últimos cinco anos, segundo os critérios clínicos descritos por Danish, em 1982. O registro mais antigo foi feito em 1981 e o mais recente de junho de 2006. Resultados: Foram encontrados 62 casos de genitália ambígua: 26 com registro do sexo feminino e 36 com registro do sexo masculino. O diagnóstico mais freqüente foi o de hiperplasia congênita de supra-renal (33,9%), seguido de quadros sindrômicos (14,5%) e disgenesias gonadais (9,7%). A média de idade ao diagnóstico foi de 7,2 anos (de zero a 42 anos). Conclusões: A ambigüidade genital não é uma doença específica, mas um conjunto de alterações que direcionam o clínico a buscar diagnósticos específicos. A freqüência dessa afecção depende dos critérios diagnósticos utilizados. A adoção de critérios amplos aumenta a chance de detecção precoce do quadro bem como de cuidado adequado a crianças com distúrbios da diferenciação sexual.

Objective: To report patients with ambiguous genitalia assisted at the State Institute of Diabetes and Endocrinology of Rio de Janeiro, Brazil, in the last five years.Methods: Retrospective chart review of all cases of ambiguous genitalia, classified according to Danish criteria (1982), who attended follow-up visits in the last five years. The oldest record is from 1981 and the most recent one, 2006. Results: 62 patients with ambiguous genitalia were found: 26 of them assigned as females and 36 as males. The most frequent diagnosis was congenital adrenal hyperplasia (33.9%), followed by syndromic diseases (14.5%) and gonadal dysgenesis (9.7%). The majority of patients with ambiguous genitalia were detected at birth, however, the mean age at the diagnosis was 7.2 years (zero to 42 years).Conclusions: Genital ambiguity is not a specific disease, but a set of problems that directs the physician to search specific diagnosis. The frequency of this condition depends on the diagnostic criteria used. Adopting amplified criteria in order to diagnose genital ambiguity will increase the possibility of early detention and adequate handling of these patients.