Metal Fume Fever: An Underdiagnosis.

Metal fume fever (MFF) is an auto-limited acute febrile respiratory syndrome that may mimic an acute viral respiratory disease after exposure to the fumes of metal oxides. Due to the similar presentation of an influenza-like illness, it remains an underdiagnosed disease. It is typically a benign and self-limited entity that resolves over 12-48 hours following cessation of exposure, but symptoms may reoccur with repeated exposure. Supportive and symptomatic care is recommended.

Accuracy of Doppler ultrasound in the diagnosis of giant cell arteritis: a systematic review and meta-analysis.

BACKGROUND: Giant cell arteritis (GCA) is the most common primary systemic vasculitis in people 50 years of age and over, and it is considered a medical emergency due to the potential risk of permanent visual loss. Color Doppler ultrasound (CDU) of the temporal arteries is a rapid, noninvasive method to diagnose GCA. This study aims to determine the diagnostic accuracy of the halo sign in temporal arteries by CDU in people with suspected GCA. METHODS: The systematic literature review included the search for publications in the following electronic databases: PubMed, Embase, CENTRAL, LILACS, WHO ICTRP, ClinicalTrials.gov, gray literature up to December 2022, and no date or language restrictions were applied. We analyzed studies including patients over 50 years of age with suspected GCA evaluating CDU of temporal arteries as a diagnostic tool against clinical diagnosis as a standard reference. Paper titles and abstracts were selected by two investigators independently for all available records. The quality of the studies was assessed using the Quality of Diagnostic Accuracy Studies tool (QUADAS-2) and the R software (version 4.2.1) was used for data analysis. The protocol of this review is registered with PROSPERO (CRD42016033079). RESULTS: Twenty-two studies including 2893 participants with suspected GCA who underwent temporal artery CDU were evaluated. The primary analysis results showed a sensitivity of 0.76 [95% confidence interval (95 CI) 0.69-0.81] and specificity of 0.93 (95 CI 0.89-0.95) when the halo sign was compared to clinical diagnosis. The sensitivity value of 0.84 (95 CI 0.72-0.92) and specificity of 0.95 (95 CI 0.88-0.98) were found in five studies involving 1037 participants that analyzed the halo sign and temporal artery compression sign. A sensitivity of 0.86 (95 CI 0.78-0.91) and specificity of 0.95 (95 CI 0.89-0.98) were found in four studies with 603 participants where the halo sign was evaluated CDU on temporal and axillary arteries. CONCLUSION: The detection of the halo sign by CDU of temporal arteries has good accuracy for the diagnosis of cranial GCA. The compression sign in temporal arteries and the addition of axillary arteries assessment improves the diagnostic performance of CDU for GCA. TRIAL REGISTRATION: PROSPERO CRD42016046860.

Accuracy of Doppler ultrasound in the diagnosis of giant cell arteritis: a systematic review and meta-analysis

Abstract Background Giant cell arteritis (GCA) is the most common primary systemic vasculitis in people 50 years of age and over, and it is considered a medical emergency due to the potential risk of permanent visual loss. Color Doppler ultrasound (CDU) of the temporal arteries is a rapid, noninvasive method to diagnose GCA. This study aims to determine the diagnostic accuracy of the halo sign in temporal arteries by CDU in people with suspected GCA. Methods The systematic literature review included the search for publications in the following electronic databases: PubMed, Embase, CENTRAL, LILACS, WHO ICTRP, ClinicalTrials.gov, gray literature up to December 2022, and no date or language restrictions were applied. We analyzed studies including patients over 50 years of age with suspected GCA evaluating CDU of temporal arteries as a diagnostic tool against clinical diagnosis as a standard reference. Paper titles and abstracts were selected by two investigators independently for all available records. The quality of the studies was assessed using the Quality of Diagnostic Accuracy Studies tool (QUADAS-2) and the R software (version 4.2.1) was used for data analysis. The protocol of this review is registered with PROSPERO (CRD42016033079). Results Twenty-two studies including 2893 participants with suspected GCA who underwent temporal artery CDU were evaluated. The primary analysis results showed a sensitivity of 0.76 [95% confidence interval (95 CI) 0.69-0.81] and specificity of 0.93 (95 CI 0.89-0.95) when the halo sign was compared to clinical diagnosis. The sensitivity value of 0.84 (95 CI 0.72-0.92) and specificity of 0.95 (95 CI 0.88-0.98) were found in five studies involving 1037 participants that analyzed the halo sign and temporal artery compression sign. A sensitivity of 0.86 (95 CI 0.78-0.91) and specificity of 0.95 (95 CI 0.89-0.98) were found in four studies with 603 participants where the halo sign was evaluated CDU on temporal and axillary arteries. Conclusion The detection of the halo sign by CDU of temporal arteries has good accuracy for the diagnosis of cranial GCA. The compression sign in temporal arteries and the addition of axillary arteries assessment improves the diagnostic performance of CDU for GCA. Trial registration PROSPERO CRD42016046860.

Concomitant Nitrofurantoin-Induced Autoimmune Hepatitis and Interstitial Lung Disease.

Antibiotics are known to cause adverse reactions, but multiple organ involvement associated with nonspecific symptoms can lead to a delay in diagnosis. A definitive correlation between each toxin and its effects is difficult to establish due to concomitant potential toxins in the circulation. This article highlights an uncommon case of concomitant nitrofurantoin-induced autoimmune hepatitis and lung fibrosis that fulfills the definitive clinical criteria for diagnosis, presenting histological, imagiological, and immunological evidence of nitrofurantoin-induced toxicity. It occurred in a 68-year-old woman with extended nitrofurantoin intake for urinary tract infection prophylaxis who presented with progressive exercise dyspnea and jaundice. Similar published cases are also reviewed in this article.

Os antibióticos são causas conhecidas de reações adversas, mas o envolvimento multiorgânico associado à sintomatologia inespecífica pode conduzir ao atraso diagnóstico. Devido às potenciais toxinas concomitantemente em circulação, é muitas vezes difícil estabelecer uma correlação definitiva entre cada toxina e os seus efeitos.Este artigo salienta um caso incomum de hepatite autoimune e fibrose pulmonar induzidas pela nitrofurantoína e que cumpre critérios definitivos de diagnóstico, apresentando-se dados histológicos, imagiológicos e imunológicos da toxicidade induzida pela nitrofurantoína.O caso ocorre numa mulher de 68 anos de idade, com toma prolongada de nitrofurantoína como profilaxia de infeção urinária, e que se apresenta com dispneia de esforço progressiva e icterícia. O artigo faz ainda uma revisão de casos semelhantes publicados.

Leaf coordination between petiole vascular development and water demand in response to elevated CO2 in tomato plants.

The rise in atmospheric CO2 has a profound impact on plants physiology and performance. Stomatal gas exchange such as reduction in water loss via transpiration and higher photosynthetic rates are among the key plant physiological traits altered by the increase of CO2. Water acquired in plant roots is transported via the xylem vessels to the shoots. Under conditions of elevated CO2, water flux decreases due to higher water use efficiency and a decline in stomatal conductance. However, the mechanism by which the shoot vascular development is affected under elevated CO2 is still largely unclear in herbaceous crops. In the current study, tomato plants were exposed to either 400 or 800 ppm of CO2 and were analyzed for growth, leaf area, gas exchange rate, and petiole anatomy. Elevated CO2 caused a reduction in metaxylem vessel diameter, which in turn, decreased leaf theatrical conductivity by 400% as compared with plants grown under ambient CO2. This work links anatomical changes in the petioles to the rise in atmospheric CO2 and water use. Plant water demand declined under elevated CO2, while photosynthesis increased. Thus, the decrease in leaf specific conductivity was attributed to lower water consumption in leaf gas exchange and, by extension, to higher leaf water use efficiency. As the global climate changes and water scarcity becomes more common, such anatomical alterations caused by elevated CO2 may affect plant response to water limitation. Further research on petiole anatomical alterations under conditions of combined climate change factors such as drought and heat with elevated CO2 may assist in clarifying the responses expected by future climate scenarios.

Resilience Programs for Children and Adolescents: A Systematic Review and Meta-Analysis.

Resilience may be defined as the ability to recover and adapt to adverse situations. Given that resilience involves cognitive and behavioral aspects, it could be promoted based on strategies that favor them, especially during childhood and adolescence. As a result, several resilience-focused programs have been developed and studied. This systematic review of Randomized Controlled Trials (RCTs) aimed to assess resilience-focused programs for children (<12 years old) and adolescents (12-22 years old) compared to active (treatment as usual, other program modalities, and educational curriculum at school) or inactive (waiting list, no treatment) control groups. We performed a systematic review of meta-analyses of RCTs. The following databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and PsycINFO. Two authors independently selected the studies, extracted the data, and assessed the studies' risk of bias. Meta-analyses of random effects were conducted to calculate the standard mean differences (SMD) and 95% confidence interval (CI) of program effectiveness. Of the 17 RCTs that met the inclusion criteria, 13 provided sufficient data to assess the effectiveness of the programs after their implementation. Meta-analyses indicated overall effectiveness of the programs in promoting resilience (SMD = 0.48, 95% CI [0.15, 0.81], p = 0.0077). The subgroup analysis indicated effectiveness only among adolescents' resilience (SMD = 0.48, 95% CI [0.08, 0.88], p = 0.02). The follow-up analysis also indicated evidence of continuation of results within a period of up to 6 months up (SMD = 0.12, 95% CI [-0.44, 0.69], p = 0.02). These results indicated the effectiveness of promoting resilience, especially in adolescents, and its continuation in follow-up analyses. These findings are promising in the field of resilience programs; however, further studies are necessary to analyze the different possible characteristics of programs and their results. Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020179874], [CRD42020179874].

O uso da telemedicina em tempos de COVID: sinopse de evidências / The use of telemedicine in COVID times: synopsis of evidence

Contextualização: A necessidade do distanciamento social para prevenção da transmissão da COVID-19 permitiu o uso da telemedicina para o atendimento on-line de pacientes em determinadas situações em que o contato direto profissional/paciente não fosse estritamente necessário. Objetivo: Desenvolver uma síntese baseada nas melhores evidências científicas disponíveis sobre o uso da telemedicina no contexto da pandemia de COVID-19. Desenho de estudo: Sinopse de evidências. Metodologia: Realizou-se a busca por estudos com maiores níveis de evidências nas bases de dados Medline/PubMed, na Cochrane Library e na Embase. A busca foi realizada em junho de 2021, não houve restrição de idioma. Resultados: Foram localizadas 157 citações, sendo 81 no MEDLINE/PubMed; 10 na Cochrane Library e 66 na Embase. Seis estudos foram incluídos, destes, cinco eram revisões sistemáticas e uma revisão de escopo. Os estudos incluídos pertenciam a diferentes áreas médicas como dermatologia e emergência médica. Esses estudos foram realizados principalmente na América do Norte, Europa e Ásia. Discussão: A maioria dos estudos são provenientes de estudos observacionais e concordam que o uso da telemedicina durante a pandemia foi favorável nas mais variadas especialidades, principalmente na coleta de dados para a triagem. Conclusões: Houve um aumento considerável do uso da telemedicina durante a pandemia da COVID-19, em âmbito tanto hospitalar como ambulatorial. As consultas a distância proporcionaram proteção e segurança tanto aos pacientes como aos profissionais de saúde. Os pacientes apresentaram-se satisfeitos com o atendimento virtual. No entanto, muitos são os desafios a serem superados para implementação da telemedicina como um todo.

Unexpected inferior vena cava syndrome: leiomyosarcoma.

Leiomyosarcomas arising directly from the blood vessels are rare. These tumours are formed from the muscular wall of either a major vein or artery. The authors describe the case of an 84-year-old woman with lower back pain with bilateral abdominal irradiation and marked peripheral oedema, who was diagnosed with leiomyosarcoma of the inferior vena cava after biopsy of an infrahepatic mass. An endovascular prosthesis was placed as the patient was proposed for palliative care. Leiomyosarcomas of the inferior vena cava may present with non-specific symptoms. Therefore, the authors aim to draw attention to the diagnosis process, as well as imaging findings related to this pathology.

Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome.

BACKGROUND: The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates. OBJECTIVES: To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020). SELECTION CRITERIA: Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment. TYPES OF PARTICIPANTS: women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment. PRIMARY OUTCOME MEASURES: live birth rate, incidence of ovarian hyperstimulation syndrome. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach. MAIN RESULTS: This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I2 = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I2 = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I2 = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I2 = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I2 = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I2 = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision. AUTHORS' CONCLUSIONS: This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman.

Pharmacological treatment for Buerger's disease.

BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure). AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

Ketogenic Diet for Refractory Childhood Epilepsy: Beyond Seizures Control, the Experience of a Portuguese Pediatric Centre.

INTRODUCTION: Ketogenic diet is a low carbohydrate diet, which can be used as a treatment for refractory childhood epilepsy. The first aim of this study was to evaluate its efficacy, in patients receiving ketogenic diet for at least three months, on epilepsy control, behaviour and awareness. The secondary aims were to evaluate the variation in the number of antiepileptic drugs, reasons for discontinuing the diet and adverse effects. MATERIAL AND METHODS: Retrospective analysis of clinical records of patients who underwent ketogenic diet for refractory epilepsy, from October 2007 to January 2018, in a tertiary pediatric hospital. RESULTS: In the twenty-nine eligible patients, the mean age of initiation was 7.9 years-old (+/- 5.6). Of those, 18 had a ≥ 50% reduction of seizure activity, 19 a marked behaviour improvement and 18 improved awareness. The median number of antiepileptic drugs remained equal for the 15 patients who completed 18 months of treatment (three drugs). The main reason for discontinuing ketogenic diet was a familiar decision. The main adverse effects were hypercholesterolemia (n = 23) and hypertriglyceridemia (n = 21). DISCUSSION: Results were comparable to those of other cohorts, namely age of initiation, proportion of patients completing ketogenic diet, most frequent reasons for stopping and significant improvement of alertness and behavior. CONCLUSION: Beyond seizure control, patients experienced a marked improvement in behavior and awareness. It is necessary to develop strategies to increase the adherence of families to the diet.

Introdução: A dieta cetogénica é uma dieta com baixo teor de hidratos de carbono, que pode ser usada no tratamento da epilepsia infantil refratária. O principal objetivo deste estudo foi avaliar a eficácia nos doentes que completaram pelo menos três meses de dieta, no que respeita ao controlo das crises, comportamento e estado de alerta. Foi também avaliada a variação do número de fármacos antiepiléticos, as razões de descontinuação e os efeitos secundários. Material e Métodos: Análise retrospetiva dos processos clínicos dos doentes com epilepsia refratária sob dieta cetogénica, de outubro de 2007 a janeiro de 2018, num hospital pediátrico de nível 3. Resultados: Nos 29 doentes elegíveis, a média da idade de implementação foi 7,9 anos (+/­ 5,6). Destes, 18 tiveram uma redução ≥ 50% das crises, 19 tiveram uma melhoria marcada do comportamento e 18 do seu estado de alerta. Dos 15 que completaram 18 meses, a mediana do número de fármacos antiepiléticos permaneceu idêntica à do início (três fármacos). A principal razão de descontinuação foi por decisão familiar. Os principais efeitos secundários foram a hipercolesterolémia (n = 23) e a hipertrigliceridémia (n = 21). Discussão: Os resultados foram semelhantes aos obtidos noutras coortes, nomeadamente no que respeita à idade de início, à percentagem de doentes que completou a dieta, às razões da suspensão e à melhoria do comportamento e estado de alerta. Conclusão: Para além do controlo das crises, os doentes tiveram uma marcada melhoria do seu comportamento e estado de alerta. É necessário desenvolver estratégias para aumentar a adesão das famílias à dieta.

lilacs search strategy for systematic reviews of diagnostic test accuracy studies.

BACKGROUND: There are few publications on search strategies to identify diagnostic test accuracy (DTA) studies in lilacs. OBJECTIVE: To translate and customise medline search strategies for use in lilacs and assess their retrieval of studies in Cochrane DTA systematic reviews. METHOD: We developed a six-step process to translate and customise medline search strategies for use in lilacs (iAHx interface). We identified medline search strategies of published Cochrane DTA reviews, translated/customised them for use in lilacs, ran searches in lilacs and compared the retrieval results of our translated search strategy versus the one used in the published reviews. RESULTS: Our lilacs search strategies translated/customised from the medline strategies retrieved studies in 70 Cochrane DTA reviews. Only 29 of these reviews stated that they had searched the lilacs database and 21 published their lilacs search strategies. Few had used the lilacs database search tools, none exploded the subject headings, and 86% used only English terms. CONCLUSION: Translating and tailoring a medline search strategy for the lilacs database resulted in the retrieval of DTA studies that would have been missed otherwise.

Esthetic perception of changes in facial profile resulting from orthodontic treatment with extraction of premolars: A systematic review.

BACKGROUND: The authors conducted a systematic review to assess changes in patients' facial profiles resulting from orthodontic treatment with and without extraction of 4 premolars and to identify cephalometric parameters that can assist decision making in borderline cases. TYPES OF STUDIES REVIEWED: The authors conducted a systematic review of randomized clinical trials and observational studies comparing the 2 types of treatment (with and without premolar extraction) in terms of the changes in facial profile. The authors conducted an electronic search of the databases the Cochrane Library, PubMed MEDLINE, Embase, and Latin-American and Caribbean Health Sciences Literature. RESULTS: The authors identified 1 clinical trial with 26 participants and 5 observational cohort studies, collectively involving 362 participants. The authors assessed cephalometric parameters and esthetic outcomes. Four studies used linear regression analysis to investigate esthetic interaction between treatment strategy and initial lower lip protrusion. The 4 studies determined that if the initial lip protrusion was beyond a determined point, esthetic preferences favored extraction, and if the initial lip protrusion was not to that point, esthetic preferences favored conservative treatment. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The results of the authors' systematic review found no significant differences between the groups in terms of the esthetic outcomes. The cephalometric parameter of initial lip protrusion can help with decision making in borderline cases.

Statins for aortic valve stenosis

ABSTRACT BACKGROUND: Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. OBJECTIVES: To evaluate the effectiveness and safety of statins in aortic valve stenosis. METHODS: Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions. Selection criteria: Randomized controlled clinical trials (RCTs) comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. Data collection and analysis: Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity), freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalization for any reason, overall mortality, adverse events and patient quality of life. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO) was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. MAIN RESULTS: We included four RCTs with 2360 participants comparing statins (1185 participants) with placebo (1175 participants). We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD) -0.54, 95% confidence interval (CI) -1.88 to 0.80; participants = 1935; studies = 2), valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2), and aortic jet velocity (MD -0.06, 95% CI -0.26 to 0.14; participants = 155; study = 1). Moderate-quality evidence showed no effect on freedom from valve replacement with statins (risk ratio (RR) 0.93, 95% CI 0.81 to 1.06; participants = 2360; studies = 4), and no effect on muscle pain as an adverse event (RR 0.91, 95% CI 0.75 to 1.09; participants = 2204; studies = 3; moderate-quality evidence). Low- and very low-quality evidence showed uncertainty around the effect of statins on death from cardiovascular cause (RR 0.80, 95% CI 0.56 to 1.15; participants = 2297; studies = 3; low-quality evidence) and hospitalization for any reason (RR 0.84, 95% CI 0.39 to 1.84; participants = 155; study = 1; very low-quality evidence). None of the four included studies reported on overall mortality and patient quality of life. AUTHORS CONCLUSIONS: Result findings showed uncertainty surrounding the effect of statins for aortic valve stenosis. The quality of evidence from the reported outcomes ranged from moderate to very low. These results give support to European and USA guidelines (2012 and 2014, respectively) that so far there is no clinical treatment option for aortic valve stenosis.

Chewing gum for enhancing early recovery of bowel function after caesarean section.

BACKGROUND: Caesarean sections (CS) are the most frequent major surgery in the world. A transient impairment of bowel motility is expected after CS. Although this usually resolves spontaneously within a few days, it can cause considerable discomfort, require symptomatic medication and delay hospital discharge, thus increasing costs. Chewing gum in the immediate postoperative period is a simple intervention that may be effective in enhancing recovery of bowel function in other types of abdominal surgeries. OBJECTIVES: To assess the effects of chewing gum to reduce the duration of postoperative ileus and to enhance postoperative recovery after a CS. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 June 2016), LILACs (20 June 2016), ClinicalTrials.gov (20 June 2016), WHO International Clinical Trials Registry Platform (ICTRP) (20 June 2016) and the reference lists of retrieved studies. SELECTION CRITERIA: All randomised controlled trials comparing chewing gum versus usual care, for women in the first 24 hours after a CS. We included studies published in abstract form only.Quasi-randomised, cross-over or cluster-randomised trials were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, extracted data and assessed the risk of bias following standard Cochrane methods. We present dichotomous outcome results as risk ratio (RR) with 95% confidence intervals (CI) and continuous outcome results as mean differences (MD) and 95% CI. We pooled the results of similar studies using a random-effects model in case of important heterogeneity. We used the GRADE approach to assess the overall quality of evidence. MAIN RESULTS: We included 17 randomised trials (3149 participants) conducted in nine different countries. Seven studies (1325 women) recruited exclusively women undergoing elective CS and five studies (833 women) only included women having a primary CS. Ten studies (1731 women) used conventional feeding protocols (nil by mouth until the return of intestinal function). The gum-chewing regimen varied among studies, in relation to its initiation (immediately after CS, up to 12 hours later), duration of each session (from 15 to 60 minutes) and number of sessions per day (three to more than six). All the studies were classified as having a high risk of bias due to the nature of the intervention, women could not be blinded and most of the outcomes were self-reported.Primary outcomes of this review: for the women that chewed gum, the time to passage of first flatus was seven hours shorter than those women in the 'usual care' control group (MD -7.09 hours, 95% CI -9.27 to -4.91 hours; 2399 women; 13 studies; random-effects Tau² = 14.63, I² = 95%, very low-quality evidence). This effect was consistent in all subgroup analyses (primary and repeat CS, time spent chewing gum per day, early and conventional feeding protocols, elective and non-elective CS and time after CS when gum-chewing was initiated). The rate of ileus was on average over 60% lower in the chewing-gum group compared to the control (RR 0.39, 95% CI 0.19 to 0.80; 1139 participants; four studies; I² = 39%, low-quality evidence). Tolerance to gum-chewing appeared to be high. Three women in one study complained about the chewing gum (but no further information was provided) and none of the studies reported adverse effects (eight studies, 925 women, low-quality evidence).Secondary outcomes of this review: the time to passage of faeces occurred on average nine hours earlier in the intervention group (MD -9.22 hours, 95% CI -11.49 to -6.95 hours; 2016 participants; 11 studies; random-effects Tau² = 12.53, I² = 93%, very low-quality evidence). The average duration of hospital stay was shorter in the intervention compared to the control group (MD -0.36 days, 95% CI -0.53 to -0.18 days; 1489 participants; seven studies; random-effects Tau² = 0.04, I² = 92%). The first intestinal sounds were heard earlier in the intervention than in the control group (MD -4.56 hours, 95% CI -6.18 to -2.93 hours; 1729 participants; nine studies; random-effects Tau² = 5.41, I² = 96%). None of the studies assessed women's satisfaction in relation to having to chew gum. The need for analgesia or antiemetic agents did not differ between the intervention and control groups (average RR 0.50, 95% CI 0.12 to 2.13; 726 participants; three studies; random-effects Tau² = 0.79, I² = 69%). AUTHORS' CONCLUSIONS: This review found 17 randomised controlled trials (involving 3149 women). We downgraded the quality of the evidence for time to first passage of flatus and of faeces and for adverse effects/intolerance to gum chewing because of the high risk of bias of the studies (due to lack of blinding and self-report). For time to first flatus and faeces, we downgraded the quality of the evidence further because of the high heterogeneity in these meta-analyses and the potential for publication bias based on the visual inspection of the funnel plots. The quality of the evidence for adverse effects/tolerance to gum chewing and for ileus was downgraded because of the small number of events. The quality of the evidence for ileus was further downgraded due to the unclear risk of bias for the assessors evaluating this outcome.The available evidence suggests that gum chewing in the immediate postoperative period after a CS is a well tolerated intervention that enhances early recovery of bowel function. However the overall quality of the evidence is very low to low.Further research is necessary to establish the optimal regimen of gum-chewing (initiation, number and duration of sessions per day) to enhance bowel function recovery and to assess potential adverse effects of and women's satisfaction with this intervention. New studies also need to assess the compliance of the participants to the recommended gum-chewing instructions. Future large, well designed and conducted studies, with better methodological and reporting quality, will help to inform future updates of this review and enhance the body of evidence for this intervention.

Statins for aortic valve stenosis.

BACKGROUND: Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. OBJECTIVES: To evaluate the effectiveness and safety of statins in aortic valve stenosis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions. SELECTION CRITERIA: Randomised controlled clinical trials (RCTs) comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. DATA COLLECTION AND ANALYSIS: Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity), freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalisation for any reason, overall mortality, adverse events and patient quality of life.Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO) was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. MAIN RESULTS: We included four RCTs with 2360 participants comparing statins (1185 participants) with placebo (1175 participants). We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD) -0.54, 95% confidence interval (CI) -1.88 to 0.80; participants = 1935; studies = 2), valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2), and aortic jet velocity (MD -0.06, 95% CI -0.26 to 0.14; participants = 155; study = 1). Moderate-quality evidence showed no effect on freedom from valve replacement with statins (risk ratio (RR) 0.93, 95% CI 0.81 to 1.06; participants = 2360; studies = 4), and no effect on muscle pain as an adverse event (RR 0.91, 95% CI 0.75 to 1.09; participants = 2204; studies = 3; moderate-quality evidence). Low- and very low-quality evidence showed uncertainty around the effect of statins on death from cardiovascular cause (RR 0.80, 95% CI 0.56 to 1.15; participants = 2297; studies = 3; low-quality evidence) and hospitalisation for any reason (RR 0.84, 95% CI 0.39 to 1.84; participants = 155; study = 1; very low-quality evidence). None of the four included studies reported on overall mortality and patient quality of life. AUTHORS' CONCLUSIONS: Result findings showed uncertainty surrounding the effect of statins for aortic valve stenosis.The quality of evidence from the reported outcomes ranged from moderate to very low. These results give support to European and USA guidelines (2012 and 2014, respectively) that so far there is no clinical treatment option for aortic valve stenosis.

Polyunsaturated fatty acid supplementation for drug-resistant epilepsy.

BACKGROUND: An estimated 1% to 3% of all individuals will receive a diagnosis of epilepsy during their lives, which corresponds to approximately 50 million affected people worldwide. The real prevalence is possibly higher because epilepsy is underreported in developing countries. Although most will achieve adequate control of their disease though the use of medication, approximately 25% to 30% of all those with epilepsy are refractory to pharmacological treatment and will continue to have seizures despite the use of two or more agents in adequate dosages. Over the last decade, researchers have tested the use of polyunsaturated fatty acid (PUFA) supplements for the treatment of refractory epilepsy, with inconsistent results. There have also been some concerns about the use of omega-3 PUFA compounds because they reduce platelet aggregation and could, in theory, cause bleeding. OBJECTIVES: To assess the effectiveness and tolerability of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid-EPA and docosahexanoic acid-DHA) in the control of seizures in people with refractory epilepsy. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (from inception up to November 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, issue 11), MEDLINE (1948 to November 2015), EMBASE (1980 to November 2015), SCOPUS (1823 to November 2015); LILACS (Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde) (1982 to November 2015); ClinicalTrials.gov; World Health Organization (WHO) International Clinical Trials Registry Platform (November 2015). No language restrictions were imposed. We contacted study authors for additional and unpublished information and screened the reference lists of retrieved citations for potentially eligible studies not identified through the electronic search. SELECTION CRITERIA: All randomised and quasi-randomised studies using PUFAs for the treatment of drug-resistant epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors were involved in study selection, data extraction and quality assessment of the included trials. The following outcomes were assessed: seizure freedom, seizure reduction, improvement in quality of life, potential adverse effects, gastrointestinal effects, drop-out rates and changes in plasma lipid profile. Primary analyses were by intention to treat. MAIN RESULTS: Eight studies were identified as potentially relevant; three fulfilled the selection criteria and were included in the review. Two placebo-controlled, double blind trials involving adult participants were conducted in developed countries, while one placebo-controlled, single blind trial involving children was conducted in a developing country (Egypt). Bromfield 2008 randomised 27 American adults to receive 2.2 g/day of omega-3 PUFAs (EPA:DHA in a 3:2 ratio) or placebo. Yuen 2005 randomised 58 people in the UK to approximately 1.7 g/day omega-3 PUFAs (1g EPA and 0.7g DHA) or placebo. Reda 2015 randomised 70 Egyptian children to receive 3 ml/day of 1200 mg fish oil (providing 0.24 g DHA and 0.36 g EPA) or placebo. The three studies recruited a total of 155 subjects (85 adults and 70 children); 78 of them (43 adults and 35 children) were randomised to PUFAs and 77 (42 adults and 35 children) to placebo. All participants were followed for up to 12 weeks. Seizure freedom was reported by only one study, with a high risk of bias, involving exclusively children. The risk estimate for this outcome was significantly higher in the children receiving PUFA compared to the control group (risk ratio (RR) 20.00, 95% confidence interval (CI) 2.84 to 140.99, 1 study, 70 children). Similarly, PUFA supplementation was associated with a significant difference in the proportion of children with at least 50% reduction in seizure frequency (RR 33.00 95% CI 4.77 to 228.15, 1 study with a high risk of bias, 70 children). However, this effect was not observed when the data from two studies including adult participants were pooled (RR 0.57, 95% CI 0.19 to 1.75, I² 0%, 2 studies, 78 participants, low-quality evidence). One of our three primary outcomes (adverse effects related to bleeding) was not assessed in any of the studies included in this review. There were no significant differences between the PUFA and control groups in relation to gastrointestinal effects (RR 0.78, 95% CI 0.32 to 1.89, 2 studies, 85 participants, low-quality evidence).Supplementation with PUFA did not produce significant differences in mean frequency of seizures, quality of life or other side effects. AUTHORS' CONCLUSIONS: In view of the limited number of studies and small sample sizes, there is not enough evidence to support the use of PUFA supplementation in people with refractory epilepsy. More trials are needed to assess the benefits of PUFA supplementation in the treatment of drug-resistant epilepsy.

Pharmacological treatment for Buerger's disease.

BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure. AUTHORS' CONCLUSIONS: Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.