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Objectives: Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. Methods: At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications (‘red shading’ in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. Results: Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3–8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40–7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08–0.65) for 2015–2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). Conclusion: In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Part

Objectives: Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. Methods: At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications (‘red shading’ in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. Results: Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3–8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40–7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08–0.65) for 2015–2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). Conclusion: In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Part

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Metabolic epilepsies arise in the context of rare inborn errors of metabolism (IEM), notably glucose transporter type 1 deficiency syndrome, succinic semialdehyde dehydrogenase deficiency, pyruvate dehydrogenase complex deficiency, nonketotic hyperglycinemia, and mitochondrial cytopathies. A common feature of these disorders is impaired bioenergetics, which through incompletely defined mechanisms result in a wide spectrum of neurological symptoms, such as epileptic seizures, developmental delay, and movement disorders. The ketogenic diet (KD) has been successfully utilized to treat such conditions to varying degrees. While the mechanisms underlying the clinical efficacy of the KD in IEM remain unclear, it is likely that the proposed heterogeneous targets influenced by the KD work in concert to rectify or ameliorate the downstream negative consequences of genetic mutations affecting key metabolic enzymes and substrates-such as oxidative stress and cell death. These beneficial effects can be broadly grouped into restoration of impaired bioenergetics and synaptic dysfunction, improved redox homeostasis, anti-inflammatory, and epigenetic activity. Hence, it is conceivable that the KD might prove useful in other metabolic disorders that present with epileptic seizures. At the same time, however, there are notable contraindications to KD use, such as fatty acid oxidation disorders. Clearly, more research is needed to better characterize those metabolic epilepsies that would be amenable to ketogenic therapies, both experimentally and clinically. In the end, the expanded knowledge base will be critical to designing metabolism-based treatments that can afford greater clinical efficacy and tolerability compared to current KD approaches, and improved long-term outcomes for patients.

IntroductionThe outcomes of transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with hepatic encephalopathy (HE) are controversial. We studied the relationship of pre-TIPS HE in patients undergoing TIPS for refractory ascites on all-cause mortality and development of post-TIPS HE.MethodsA single-center retrospective comparison study was performed for patients undergoing TIPS for refractory ascites. Survival by history of pre-TIPS HE was demonstrated with Kaplan-Meier curves. Univariate and multivariate logistic regression analyses were performed to identify the predictors of post-TIPS clinical outcomes for patients with and without pre-TIPS HE.ResultsWe identified 202 TIPS recipients (61% male, mean ± SD; age 59.1 ± 10.2 years; mean model for end-stage liver disease score 17.3 ± 6.9). Pre-TIPS HE did not predispose patients for increased all-cause mortality, increased risk of experiencing HE within 60 days, or increased risk of hospital admission for HE within 6 months. A multivariate analysis demonstrated that total bilirubin (odds ratio [OR] 1.03; P = 0.016) and blood urea nitrogen (OR 1.15; P = 0.002) were predictors for all-cause mortality within 6 months post-TIPS. Age ≥65 years (OR 3.92; P = 0.004), creatinine (OR 2.22; P = 0.014), and Child-Pugh score (OR 1.53; P = 0.006) were predictors for HE within 60 days post-TIPS. Predictors of intensive care admission for HE within 6 months post-TIPS included age ≥65 years (OR 8.84; P = 0.018), history of any admission for HE within 6 months pre-TIPS (OR 8.42; P = 0.017), and creatinine (OR 2.22; P = 0.015).DiscussionIf controlled, pre-TIPS HE does not adversely impact patient survival or clinical outcomes, such as development of HE within 60 days of TIPS or hospital admission for HE within 6 months. Patients may be able to undergo TIPS for refractory ascites despite a history of HE.

BackgroundGiven the risks of opioids, clinicians are under growing pressure to treat pain with non-opioid medications. Yet non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) have their own risks: patients with kidney disease or gastrointestinal diseases can experience serious adverse events. We examined the likelihood that patients with back pain diagnoses and contraindications to NSAIDs and opioids received an opioid prescription in primary care.MethodsWe identified office visits for back pain from 2012 to 2017 and sampled the first office visit per patient per year (N = 24,543 visits). We created indicators reflecting contraindications for NSAIDs (kidney, liver, cardiovascular/cerebrovascular, and gastrointestinal diseases; concurrent or chronic use of anticoagulants/antiplatelets, chronic corticosteroid use) and opioids (depression, anxiety, substance use (SUD) and bipolar disorders, and concurrent benzodiazepines) and estimated four logistic regression models, with the one model including all patient visits and models 2-4 stratifying for previous opioid use. We estimated the population attributable risk for each contraindication.ResultsIn our model with all patients-visits, patients received an opioid prescription at 4% of visits. The predicted probability (PP) of receiving an opioid was 4% without kidney disease vs. 7% with kidney disease; marginal effect (ME): 3%; 95%CI: 1-4%). For chronic or concurrent anticoagulant/antiplatelet prescriptions, the PPs were 4% vs. 6% (ME: 2%; 95%CI: 1-3%). For concurrent benzodiazepines, the PPs were 4% vs. 11% (ME: 7%, 95%CI: 5-9%) and for SUD, the PPs were 4% vs. 5% (ME: 1%, 95%CI: 0-3%). For the model including patients with previous long-term opioid use, the PPs for concurrent benzodiazepines were 25% vs. 24% (ME: -1%; 95%CI: - 18-16%). The population attributable risk (PAR) for NSAID and opioid contraindications was small. For kidney disease, the PAR was 0.16% (95%CI: 0.08-0.23%), 0.44% (95%

The progressive increase in numbers of noninvasive cardiac imaging examinations broadens the spectrum of knowledge radiologists are expected to acquire in the management of drugs during CT coronary angiography (CTCA) and cardiac MR (CMR) to improve image quality for optimal visualization and assessment of the coronary arteries and adequate MR functional analysis. Aim of this review is to provide an overview on different class of drugs (nitrate, beta-blockers, ivabradine, anxiolytic, adenosine, dobutamine, atropine, dipyridamole and regadenoson) that can be used in CTCA and CMR, illustrating their main indications, contraindications, efficacy, mechanism of action, metabolism, safety, side effects or complications, and providing advices in their use.

The progressive increase in numbers of noninvasive cardiac imaging examinations broadens the spectrum of knowledge radiologists are expected to acquire in the management of drugs during CT coronary angiography (CTCA) and cardiac MR (CMR) to improve image quality for optimal visualization and assessment of the coronary arteries and adequate MR functional analysis. Aim of this review is to provide an overview on different class of drugs (nitrate, beta-blockers, ivabradine, anxiolytic, adenosine, dobutamine, atropine, dipyridamole and regadenoson) that can be used in CTCA and CMR, illustrating their main indications, contraindications, efficacy, mechanism of action, metabolism, safety, side effects or complications, and providing advices in their use.

Dance movement therapy is increasingly established as an evidence-based treatment modality in health care. However, systematic knowledge on indications and contraindications of dance movement therapy (DMT) are widely lacking. In this study, we developed a questionnaire to learn from practitioners' experience with DMT intervention methods for specific patient populations. Fifty-four practitioners from ten different countries worldwide indicated the "dos and don'ts" for their main populations. These inductively and experientially gained indications and contraindications for DMT, and their justifications, fell into 22 clinical categories such as psychiatry, psychosomatics, neurology, trauma, eating disorder, pain, oncology, and treatment of specific groups such as children, adolescents, families, pregnant women or prisoners. Extensive materials resulted for each disorder. Results suggest that for clinical populations the Chace method, body image work, and movement rituals, such as circle dances, are indicated without contraindications; relaxation and inner focus are differentially indicated (e.g. inner focus is contraindicated for eating disorder and schizophrenia), whereas Authentic Movement and free improvisation are are often only indicated with high functioning participants, and contraindicated with low functioning participants (level of functioning moderated the results). Possibilities and limitations of this inductive participatory approach to investigating indications are discussed. The study contributes to defining differential disorder-specific DMT interventions, therapeutic factors of DMT, as well as new methods. Future studies should increasingly investigate indications and contraindications of DMT with diverse methods and populations.

INTRODUCTION: In 2016, 2.1 million people in the United States were estimated to have an opioid use disorder. Although the disorder can be safely and effectively treated with prescription methadone, treatment is potentially long term and may span womens peak childbearing ages. Little is known about womens reproductive health needs while on methadone. METHODS: We interviewed 22 sexually active, nonpregnant women ages 21-39 years at two Los Angeles methadone clinics in 2016. The interviews were transcribed and coded by four researchers using thematic and open coding techniques. RESULTS: One-half of the women were nulliparous and 17 were in stable, monogamous relationships with men. Women reported a range of feelings and perceptions about pregnancy, but nearly all wanted to delay pregnancy until discontinuing methadone. However, many women indicated limited interest in preventing pregnancy because of the relative stability of their relationships, fear of infertility, and low perceived risk of pregnancy. These factors influenced contraceptive use. DISCUSSION: Women described mixed feelings about pregnancy and many ultimately felt that an unplanned pregnancy would be acceptable in the context of their relationships and uncertain fertility. These findings provide context for previous quantitative findings that women in methadone treatment have higher rates of unintended pregnancy and lower rates of contraceptive use than the general population. CONCLUSIONS: Accurate information about pregnancy in the context of methadone treatment may help women to make proactive family planning decisions. Health care providers should discuss the guidelines for pregnancy on methadone and offer a range of options to help women achieve their reproductive goals.

Persons living with HIV (PLWH) are at an increased risk of contraindicated drug-drug interactions (XDDIs), which may result in deleterious outcomes. Study objectives were to (1) compare the frequency of hospitalizations between patients with and without XDDIs and (2) determine if XDDIs are independently associated with hospitalizations in PLWH. A retrospective cohort study was performed among PLWH receiving care at the Upstate New York Veterans' Healthcare Administration or University of New Mexico Truman Health Services from 2000 to 2013. Hospitalization was defined as an admission to an inpatient hospital facility for ≥24 h. Of the 1329 patients evaluated, 149 (11.2%) patients were hospitalized within 1 year of antiretroviral therapy initiation. A significantly higher proportion of patients with XDDIs were hospitalized compared with those who did not have XDDIs (20.3% vs. 10.2%, risk ratio: 1.98, 95% confidence interval [CI]: 1.35-2.91, p = .001). In the multivariate Cox proportional hazards regression analyses, XDDIs were independently associated with hospitalizations (hazard ratio [HR]: 1.58; 95% CI: 1.00-2.48; p = .05), after adjustment for CD4 < 242 cells/mm3 (HR: 2.38; 95% CI: 1.72-3.33; p < .001), protease inhibitor (PI)-based regimen (HR: 1.35; 95% CI: 0.97-1.89; p = .08), recreational drug use (HR: 2.58, 95% CI: 1.85-3.58, p < .001), and non-HIV medications ≥10 (HR: 1.62; 95% CI: 0.97-2.69; p = .07). In this study an increased risk of hospitalization was observed among PLWH with XDDIs compared with those without XDDIs. This relationship persisted after adjustment for CD4 count, use of a PI-based regimen, recreational drug use, and number of non-HIV medications.

Introduction Immediate breast reconstruction (IBR) can be offered to breast cancer patients after mastectomy. A satisfactory breast symmetry has positive effects on psychosocial morbidity, quality of life and body image. The frequency of IBR were in 2017 in Region Örebro County 4%, lower than the national target on 20%. Aim The aim is to provide an overview of the work with IBR at Örebro University Hospital in 2016, regarding frequency of IBR, work with IBR at multidisciplinary team conferences, documentation of the patient’s opinion about IBR, delayed reconstructions, patient characteristics and presence of contraindications. Material and methods This was a retrospective study of all women who underwent mastectomy at Örebro University Hospital in 2016. Results Five of the 103 women got IBR with expander implants in connection to mastectomy, additionally 28 had no contraindications for IBR. Five of the women have discussed about IBR at multidisciplinary team conferences and seven had notes about their attitude to IBR. Ten women underwent delayed reconstruction during the follow-up, additional seven patients were waiting for surgery. There were no significant differences in patient characteristics between the groups “mastectomy and IBR” and “mastectomy only”. Conclusions The low frequencies of performed IBR, discussions at multidisciplinary team conferences and documentation of the patient’s opinion about IBR indicate that there is space for a more active work about IBR. Besides the women who got IBR, there were additionally 28 women without any contraindications for IBR, indicating that there is a considerable group that can become candidates for IBR.

Persons living with HIV (PLWH) are at an increased risk of contraindicated drug-drug interactions (XDDIs), which may result in deleterious outcomes. Study objectives were to (1) compare the frequency of hospitalizations between patients with and without XDDIs and (2) determine if XDDIs are independently associated with hospitalizations in PLWH. A retrospective cohort study was performed among PLWH receiving care at the Upstate New York Veterans' Healthcare Administration or University of New Mexico Truman Health Services from 2000 to 2013. Hospitalization was defined as an admission to an inpatient hospital facility for ≥24 h. Of the 1329 patients evaluated, 149 (11.2%) patients were hospitalized within 1 year of antiretroviral therapy initiation. A significantly higher proportion of patients with XDDIs were hospitalized compared with those who did not have XDDIs (20.3% vs. 10.2%, risk ratio: 1.98, 95% confidence interval [CI]: 1.35-2.91, p = .001). In the multivariate Cox proportional hazards regression analyses, XDDIs were independently associated with hospitalizations (hazard ratio [HR]: 1.58; 95% CI: 1.00-2.48; p = .05), after adjustment for CD4 < 242 cells/mm3 (HR: 2.38; 95% CI: 1.72-3.33; p < .001), protease inhibitor (PI)-based regimen (HR: 1.35; 95% CI: 0.97-1.89; p = .08), recreational drug use (HR: 2.58, 95% CI: 1.85-3.58, p < .001), and non-HIV medications ≥10 (HR: 1.62; 95% CI: 0.97-2.69; p = .07). In this study an increased risk of hospitalization was observed among PLWH with XDDIs compared with those without XDDIs. This relationship persisted after adjustment for CD4 count, use of a PI-based regimen, recreational drug use, and number of non-HIV medications.

OBJECTIVE:To characterize the graft survivorship and clinical outcomes of osteochondral allograft transplantation (OCA) of the knee in patients with an elevated body mass index (BMI). DESIGN:Prospective data on 38 consecutive patients with a BMI ≥30 kg/m2 treated with OCA from 2000 to 2015 were reviewed. Complications, reoperations, and patient responses to validated outcome measures were examined. Failures were defined by any removal/revision of the allograft or conversion to arthroplasty. RESULTS:Thirty-one knees in 31 patients (mean age, 35.4 years [range, 17-61 years]; 87% male) met the inclusion criteria. Mean BMI was 32.9 kg/m2 (range, 30-39 kg/m2). Mean chondral defect size was 6.4 cm2 (range, 1.0-15.3 cm2). Prior to OCA, 23 patients (74%) had undergone previous surgery to the ipsilateral knee. Mean duration of follow-up was 4.1 years (range, 2-11 years). After OCA, 5 knees (13%) underwent conversion to unicompartmental (1) or total (4) knee arthroplasty. Two- and 5-year graft survivorship were 87% and 83%, respectively. At final follow-up, clinically significant improvements were noted in the pain (49.3-72.6) and physical functioning (52.9-81.3) subscales of the Short Form-36 ( P ≤ 0.001), International Knee Documentation Committee subjective form (43.5-67.0; P = 0.002), Knee Outcome Survey-Activities of Daily Living (58.2-80.4; P = 0.002), and overall condition subscale of the Cincinnati Knee Rating System (4.7-6.9; P = 0.046). CONCLUSIONS:OCA can be a successful midterm treatment option for focal cartilage defects of the knee in select patients with a BMI ≥30 kg/m2.

» The use of preoperative antibiotic prophylaxis is not supported for elective cases of patients undergoing soft-tissue hand procedures that are ≤2 hours in length. » The use of preoperative antibiotic prophylaxis is not supported for patients with diabetes undergoing elective, soft-tissue hand surgical procedures. » There is a paucity of literature evaluating the use of preoperative antibiotic prophylaxis in patients with rheumatoid arthritis, those with cardiac valves, and those taking corticosteroids; because of this, there is no evidence to vary from our general recommendations.

OBJECTIVE: To characterize the graft survivorship and clinical outcomes of osteochondral allograft transplantation (OCA) of the knee in patients with an elevated body mass index (BMI). DESIGN: Prospective data on 38 consecutive patients with a BMI ≥30 kg/m2 treated with OCA from 2000 to 2015 were reviewed. Complications, reoperations, and patient responses to validated outcome measures were examined. Failures were defined by any removal/revision of the allograft or conversion to arthroplasty. RESULTS: Thirty-one knees in 31 patients (mean age, 35.4 years [range, 17-61 years]; 87% male) met the inclusion criteria. Mean BMI was 32.9 kg/m2 (range, 30-39 kg/m2). Mean chondral defect size was 6.4 cm2 (range, 1.0-15.3 cm2). Prior to OCA, 23 patients (74%) had undergone previous surgery to the ipsilateral knee. Mean duration of follow-up was 4.1 years (range, 2-11 years). After OCA, 5 knees (13%) underwent conversion to unicompartmental (1) or total (4) knee arthroplasty. Two- and 5-year graft survivorship were 87% and 83%, respectively. At final follow-up, clinically significant improvements were noted in the pain (49.3-72.6) and physical functioning (52.9-81.3) subscales of the Short Form-36 ( P ≤ 0.001), International Knee Documentation Committee subjective form (43.5-67.0; P = 0.002), Knee Outcome Survey-Activities of Daily Living (58.2-80.4; P = 0.002), and overall condition subscale of the Cincinnati Knee Rating System (4.7-6.9; P = 0.046). CONCLUSIONS: OCA can be a successful midterm treatment option for focal cartilage defects of the knee in select patients with a BMI ≥30 kg/m2.

Introduction Immediate breast reconstruction (IBR) can be offered to breast cancer patients after mastectomy. A satisfactory breast symmetry has positive effects on psychosocial morbidity, quality of life and body image. The frequency of IBR were in 2017 in Region Örebro County 4%, lower than the national target on 20%. Aim The aim is to provide an overview of the work with IBR at Örebro University Hospital in 2016, regarding frequency of IBR, work with IBR at multidisciplinary team conferences, documentation of the patient’s opinion about IBR, delayed reconstructions, patient characteristics and presence of contraindications. Material and methods This was a retrospective study of all women who underwent mastectomy at Örebro University Hospital in 2016. Results Five of the 103 women got IBR with expander implants in connection to mastectomy, additionally 28 had no contraindications for IBR. Five of the women have discussed about IBR at multidisciplinary team conferences and seven had notes about their attitude to IBR. Ten women underwent delayed reconstruction during the follow-up, additional seven patients were waiting for surgery. There were no significant differences in patient characteristics between the groups “mastectomy and IBR” and “mastectomy only”. Conclusions The low frequencies of performed IBR, discussions at multidisciplinary team conferences and documentation of the patient’s opinion about IBR indicate that there is space for a more active work about IBR. Besides the women who got IBR, there were additionally 28 women without any contraindications for IBR, indicating that there is a considerable group that can become candidates for IBR.

Objectives: Icelandic national guidelines on place of birth list contraindications for home birth. Few studies have examined the effect of contraindication on home birth, and none have done so in Iceland. The aim of this study was to examine whether contraindications affect the outcome of planned home birth or have a different effect at home than in hospital. Methods: The study is a retrospective cohort study on the effect of contraindications for home birth on the outcome of planned home (n = 307) and hospital (n = 921) birth in 2005-2009. Outcomes were described for four different groups of women, by exposure to contraindications (unexposed vs. exposed) and planned place of birth (hospital vs. home). Linear and logistic regression analysis was used to evaluate the effect of the contraindications under study and to detect interactions between contraindications and planned place of birth. Results: The key findings of the study were that contraindications were related to higher rates of adverse maternal and neonatal outcomes, regardless of place of birth; women exposed to contraindications had higher rates of adverse outcomes in planned home birth; and healthy, unexposed women had higher rates of adverse outcomes in planned hospital birth. Contraindications significantly increased the risk of transfer in labour and postpartum haemorrhage in planned home births. Conclusion: The defined contraindications for home birth had a negative effect on maternal and neonatal outcomes in Iceland, regardless of place of birth. The study results do not contradict the current national guidelines on place of birth.

BackgroundPatient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is critically important to optimizing outcomes. There is currently no literature regarding the safety of CRS/HIPEC in patients with cirrhosis. The aim of this case series is to report the outcomes of three patients with well-compensated cirrhosis who underwent CRS/HIPEC.MethodsPatients were identified from a prospectively maintained peritoneal surface malignancy database. Patient, tumor, and operative-related details were recorded as short-term postoperative outcomes. Results were analyzed using descriptive statistics.ResultsAll patients had well-compensated (Child-Pugh Class A) cirrhosis and Eastern Cooperative Oncology Group (ECOG) performance status of 0. One patient had preoperative evidence of portal hypertension. All safely underwent CRS/HIPEC with completeness of cytoreduction (CC) scores of 0. The postoperative morbidity profile was unique, but all complications were manageable and resulted in full recovery to preoperative baseline status.ConclusionsPatient selection for CRS/HIPEC is critical for optimization of short- and long-term outcomes. This small series suggests that well-compensated cirrhosis should not be an absolute contraindication to CRS/HIPEC.

Цель работы — разработка алгоритма лечения больных саркоидозом легких на основе изучения частоты противопоказаний к назначению, серьезных побочных действий и случаев резистентности к глюкокортикостероидам (ГКС), определения оптимального препарата иммуносупрессивной терапии.Материалы и методы. Изучение частоты противопоказаний, серьезных побоч­ных действий и случаев резистентности к ГКС было проведено у 185 больных с впервые выявленным саркоидозом с поражением паренхимы легких. Сравнительное изучение эффективности и переносимости азатиоприна, лефлуномида и метотрексата проведено у 43 больных саркоидозом легких.Результаты и обсуждение. В среднем у каждого восьмого больного саркоидозом II—III стадии (12,4 %) требуется назначение иммуносупрессивной терапии уже в момент установления диагноза в связи с наличием противопоказаний к применению ГКС. В ходе ГКС-терапии потребность в лечении иммуносупрессантами возрастает в связи с серьезными побочными действиями препарата, а также по причине резистентности к ГКС-терапии в среднем до 32,4 %. То есть каждому третьему пациенту на разных этапах лечения необходимо назначение иммуносупрессантов. В лечении больных саркоидозом легких с противопоказаниями к назначению или серьезными побочными действиями ГКС альтернативная терапия азатиоприном (50 мг/сут с дальнейшим повышением дозы на 25 мг/сут каждые 2 нед до достижения максимальной) является неэффективной у большинства больных. Применение лефлуномида (20 мг/сут) увеличивает частоту регрессии саркоидоза через 3 мес терапии до 50 %. В отличие от азатиоприна и лефлуномида, метотрексат (10 мг/нед) является эффективным у большинства пациентов (73,7 %). Метотрексат отличается более благоприятным профилем безопасности — в отличие от азатиоприна и лефлуномида, на протяжении 3 мес терапии метотрексатом (10 мг/нед) серьезные побочные действия, требующие отмены препарата, не наблюдались.Выводы. Разработан алгоритм лечения больных саркоидозом легких, основан­ный на учете противопоказаний к назна, Мета роботи — розробка алгоритму лікування хворих на саркоїдоз легень на основі вивчення частоти протипоказань до призначення, серйозних побічних ефектів та випадків резистентності до глюкокортикостероїдів (ГКС), визначення оптимального препарату імуносупресивної терапії.Матеріали та методи. Вивчення частоти протипоказань, серйозних побічних ефектів і випадків резистентності до ГКС було проведено у 185 хворих на вперше виявлений саркоїдоз із ураженням паренхіми легень. Порівняльне вивчення ефективності та переносимості азатіоприну, лефлуноміду і метотрексату проведено у 43 хво­рих на саркоїдоз легень.Результати та обговорення. В середньому у кожного восьмого хворого на саркоїдоз II—III стадії (12,4 %) потрібно призначення імуносупресивної терапії вже в момент встановлення діагнозу у зв’язку з наявністю протипоказань до застосування ГКС. У ході ГКС-терапії потреба в лікуванні імуносупресантами зростає в зв’язку із серйозними побічними ефектами препарату, а також внаслідок резистентності до ГКС-терапії в середньому до 32,4 %. Тобто кожному третьому пацієнту на різних етапах лікування необхідно призначення імуносупресантів.У лікуванні хворих на саркоїдоз легень з протипоказаннями до призначення або серйозними побічними ефектами ГКС альтернативна терапія азатіоприном (50 мг/добу з подальшим підвищенням дози на 25 мг/добу кожні 2 тиж до досягнення максимальної) є неефективною у більшості хворих. Застосування лефлуноміду (20 мг/добу) збільшує частоту регресії саркоїдозу через 3 міс терапії до 50 %. На відміну від азатіоприну та лефлуноміду, метотрексат (10 мг/тиж) є ефективним у більшості пацієнтів (73,7 %).Метотрексат відрізняється більш сприятливим профілем безпеки — на відміну від азатіоприну і лефлуноміду, протягом 3 міс терапії метотрексатом (10 мг/тиж) серйозної побічної дії, що вимагала б відміни препарату, не спостерігалося.Висновки. Розроблено алгоритм лікування хворих на саркоїдоз легень, заснований на врахуванні протипоказань до призначення, серйозних побічних, Objective — to develop the algorithm of treatment of patients with pulmonary sarcoidosis, based on the data regar­ding the rate of contraindications, adverse reactions and resistance to glucocorticosteroids (GCS) and the choice of the optimal drug for immunosuppressive therapy. Materials and methods. The study involved 185 patients with newly diagnosed lung parenchyma sarcoidosis to investigate the rate of contraindications, adverse reactions and resistance to GCS was conducted. The comparative study of azathioprine, leflunomide and methotrexate efficacy was performed in 43 pulmonary sarcoidosis patients.Results and discussion. At average, every eighth patient with stage II—III pulmonary sarcoidosis (12.4 %) required the administration of immunosuppressive therapy immediately after the diagnosis established due to contraindications for GCS use. During the course of GCS treatment, the necessity to use immunosuppressive drugs increases due to development of serious side effects or resistance in up to 32.4 % of patients. That is, every third patient in different phases of treatment would require immunosuppressant drugs.In majority of patients with GSC contraindications/serious side effects, an alternative therapy with azathioprine 50 mg/day with subsequent elevation of daily dose on 25 mg/day every 2 weeks (until maximum dose reached) was not effective. The use of leflunomide (20 mg/day) increased the rate of regression of sarcoidosis after 3 months of the therapy by 50 %. Unlike azathioprine and leflunomide, methotrexate (10 mg/week) was effective in the most part of patients (73,7 %).Methotrexate had more favorable safety profile. In comparison with azathioprine and leflunomide there were no serious side effects registered during 3 months of therapy with methotrexate (10 mg/week).Conclusions. An algorithm of therapy of patients with sarcoidosis has been created, based on the taking into account the contraindications, adverse reactions and resistance to GCS and the us

У статті наведено опис клінічного випадку інфаркту міокарда з позитивним результатом після проведення тромболітичної терапії при наявності як мінімум двох відносних протипоказань., В статье представлено описание клинического случая инфаркта миокарда с положительным исходом после проведения тромболитической терапии при наличии как минимум двух относительных противопоказаний., The article describes a clinical case of myocardial infarction with a positive outcome after thrombolytic therapy with at least two relative contraindications.

BackgroundPatient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is critically important to optimizing outcomes. There is currently no literature regarding the safety of CRS/HIPEC in patients with cirrhosis. The aim of this case series is to report the outcomes of three patients with well-compensated cirrhosis who underwent CRS/HIPEC.MethodsPatients were identified from a prospectively maintained peritoneal surface malignancy database. Patient, tumor, and operative-related details were recorded as short-term postoperative outcomes. Results were analyzed using descriptive statistics.ResultsAll patients had well-compensated (Child-Pugh Class A) cirrhosis and Eastern Cooperative Oncology Group (ECOG) performance status of 0. One patient had preoperative evidence of portal hypertension. All safely underwent CRS/HIPEC with completeness of cytoreduction (CC) scores of 0. The postoperative morbidity profile was unique, but all complications were manageable and resulted in full recovery to preoperative baseline status.ConclusionsPatient selection for CRS/HIPEC is critical for optimization of short- and long-term outcomes. This small series suggests that well-compensated cirrhosis should not be an absolute contraindication to CRS/HIPEC.

OBJECTIVE: To provide expert recommendations for the safe and effective application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). PARTICIPANTS: Participants included a group of 17 expert clinicians and researchers with expertise in the clinical application of rTMS, representing both the National Network of Depression Centers (NNDC) rTMS Task Group and the American Psychiatric Association Council on Research (APA CoR) Task Force on Novel Biomarkers and Treatments. EVIDENCE: The consensus statement is based on a review of extensive literature from 2 databases (OvidSP MEDLINE and PsycINFO) searched from 1990 through 2016. The search terms included variants of major depressive disorder and transcranial magnetic stimulation. The results were limited to articles written in English that focused on adult populations. Of the approximately 1,500 retrieved studies, a total of 118 publications were included in the consensus statement and were supplemented with expert opinion to achieve consensus recommendations on key issues surrounding the administration of rTMS for MDD in clinical practice settings. CONSENSUS PROCESS: In cases in which the research evidence was equivocal or unclear, a consensus decision on how rTMS should be administered was reached by the authors of this article and is denoted in the article as expert opinion. CONCLUSIONS: Multiple randomized controlled trials and published literature have supported the safety and efficacy of rTMS antidepressant therapy. These consensus recommendations, developed by the NNDC rTMS Task Group and APA CoR Task Force on Novel Biomarkers and Treatments, provide comprehensive information for the safe and effective clinical application of rTMS in the treatment of MDD.

Objectives Icelandic national guidelines on place of birth list contraindications for home birth. Few studies have examined the effect of contraindication on home birth, and none have done so in Iceland. The aim of this study was to examine whether contraindications affect the outcome of planned home birth or have a different effect at home than in hospital. Methods The study is a retrospective cohort study on the effect of contraindications for home birth on the outcome of planned home (n = 307) and hospital (n = 921) birth in 2005–2009. Outcomes were described for four different groups of women, by exposure to contraindications (unexposed vs. exposed) and planned place of birth (hospital vs. home). Linear and logistic regression analysis was used to evaluate the effect of the contraindications under study and to detect interactions between contraindications and planned place of birth. Results The key findings of the study were that contraindications were related to higher rates of adverse maternal and neonatal outcomes, regardless of place of birth; women exposed to contraindications had higher rates of adverse outcomes in planned home birth; and healthy, unexposed women had higher rates of adverse outcomes in planned hospital birth. Contraindications significantly increased the risk of transfer in labour and postpartum haemorrhage in planned home births. Conclusion The defined contraindications for home birth had a negative effect on maternal and neonatal outcomes in Iceland, regardless of place of birth. The study results do not contradict the current national guidelines on place of birth.

BACKGROUND: First-line chemotherapy for patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma is associated with short response duration, poor survival, and high toxicity. This study assessed atezolizumab (anti-programmed death-ligand 1 [PD-L1]) as treatment for metastatic urothelial cancer in cisplatin-ineligible patients. METHODS: For this single-arm, multicentre, phase 2 study, in 47 academic medical centres and community oncology practices in seven countries in North America and Europe, we recruited previously untreated patients with locally advanced or metastatic urothelial cancer who were cisplatin ineligible. Patients were given 1200 mg intravenous atezolizumab every 21 days until progression. The primary endpoint was independently confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (central review), assessed in prespecified subgroups based on PD-L1 expression and in all patients. All participants who received one or more doses of atezolizumab were included in the primary and safety analyses. This study was registered with ClinicalTrials.gov, number NCT02108652. FINDINGS: Between June 9, 2014, and March 30, 2015, we enrolled 123 patients, of whom 119 received one or more doses of atezolizumab. At 17·2 months median follow-up, the objective response rate was 23% (95% CI 16 to 31), the complete response rate was 9% (n=11), and 19 of 27 responses were ongoing. Median response duration was not reached. Responses occurred across all PD-L1 and poor prognostic factor subgroups. Median progression-free survival was 2·7 months (2·1 to 4·2). Median overall survival was 15·9 months (10·4 to not estimable). Tumour mutation load was associated with response. Treatment-related adverse events that occurred in 10% or more of patients were fatigue (36 [30%] patients), diarrhoea (14 [12%] patients), and pruritus (13 [11%] patients). One treatment-related death (sepsis) occurred. Nine (8%) patients had

Bacterial infection of tattoos remains a common complication. Pyogenic bacteria can cause infections shortly after the tattoo is made. Severity of infection varies from minor to major, ultimately with life-threatening septicemia. Viral infections may be introduced, i.e. HVB, HVC, and HIV. The risk of infection depends on the following triad: microbial pathogen and its aggressiveness, individual resistance of the tattooed, and inoculation and exposures by the tattoo needle and in the tattoo parlor. Some infectious risks can be controlled. Persons with weaknesses can refrain from tattooing. Tattoo parlors and tattooing can be hygienic and clean albeit not sterile; much has improved helped by hygiene guidelines of professional tattooists' organizations and through control instituted by local and national authorities. Tattoo inks remain a potential source of infection difficult to control in a low-priced competitive market operating over the Internet and across national borders. Ten percent of new inks are contaminated with bacteria pathogenic to humans, independent of a claim of 'sterility'. Known brands and established manufacturers are considered safer. Work is in progress aiming at common European standards for tattoo hygiene. Doctors have a role not only in treating tattoo infections but also in reporting cases to the competent authority in their country to support the monitoring of tattoo infections at any time, as an instrument for the authority to detect local outbreaks of tattoo infections early and prevent that new tattoo customers become infected. It is a potential risk of the future that new and very aggressive bacteria not seen in the past may unexpectedly show up in the tattoo scene.

PURPOSE: Benign elective procedures give rise to heterogeneity in indication for surgery and surgical technique among specialized surgeons in a variety of surgical fields. The objective was to analyze the extent of agreement in surgical management among expert hernia surgeons when evaluating the same patient in a standardized setting.METHODS: Five Danish hernia experts answered questions concerning indication for surgery and surgical technique for 25 video recorded real-life clinical cases. The experts evaluated the patients by answering a standardized questionnaire.RESULTS: All surgeons were experienced in incisional hernia repair with a median of 253 repairs (range 164-450 repairs). Perfect overall agreement among all the experts in indication, operation type, component separation, mesh fixation and mesh position was found in only five cases (20%). Agreement in indication for surgery was present in 14 cases (56%). The most common reason for not performing surgery was due to comorbidities. Agreement in operation type (open vs. laparoscopic) was present in 10 cases (40%). Agreement in mesh fixation (absorbable tacks/non-absorbable tacks/suture/other) method was also present in 10 cases (40%). Agreement in mesh position (onlay, sublay or intraperitoneal) was found in 40% of cases. The highest overall agreement among the surgeons was observed with regard to whether patients needed component separation (yes/no), 21 cases, (84%).CONCLUSIONS: In a standardized setting, agreement in choice of treatment strategy for patients with incisional hernias was very low among experienced surgeons. A standardization of surgical decision making is desirable to develop new interventions and improve clinical outcomes.

BACKGROUND: Long-term oxygen therapy (LTOT) increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury that required contact with a health care specialist, between Sweden (a country with a strict policy regarding smoking while on LTOT) and Denmark (a country with less strict smoking policy).METHODS: This was a population-based, cohort study of patients initiating LTOT due to any cause in Sweden and Denmark. Data on diagnoses, external causes, and procedures were obtained from the Swedish and Danish National Patient Registers for inpatient and outpatient care. Patients were followed from January 1, 2000, until the first of the following: LTOT withdrawal, death, or study end (December 31, 2009). The primary end point was burn injury during LTOT.RESULTS: A total of 23,741 patients received LTOT in Denmark and 7,754 patients in Sweden. Most patients started LTOT due to COPD, both in Sweden (74%) and in Denmark (62%). The rate of burn injury while on LTOT was higher in Denmark than in Sweden; 170 (95% confidence interval [CI], 126-225) vs 85 (95% CI, 44-148) per 100,000 person-years; rate ratio 2.0 (95% CI, 1.0-4.1). The risk remained higher after adjustment for gender, age, and diagnosis in multivariate Cox regression, hazard ratio 1.8 (95% CI, 1.0-3.5). Thirty-day mortality after burn injury was 8% in both countries.CONCLUSION: Compared to Sweden, the rate of burn injury was twice as high in Denmark where smoking is not a contraindication for prescribing LTOT.

Purpose: To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. Methods: We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined “early” EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. Results: We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. Conclusions: We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access., SCOPUS: re.j, info:eu-repo/semantics/published

BACKGROUND: Long-term oxygen therapy (LTOT) increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury that required contact with a health care specialist, between Sweden (a country with a strict policy regarding smoking while on LTOT) and Denmark (a country with less strict smoking policy).METHODS: This was a population-based, cohort study of patients initiating LTOT due to any cause in Sweden and Denmark. Data on diagnoses, external causes, and procedures were obtained from the Swedish and Danish National Patient Registers for inpatient and outpatient care. Patients were followed from January 1, 2000, until the first of the following: LTOT withdrawal, death, or study end (December 31, 2009). The primary end point was burn injury during LTOT.RESULTS: A total of 23,741 patients received LTOT in Denmark and 7,754 patients in Sweden. Most patients started LTOT due to COPD, both in Sweden (74%) and in Denmark (62%). The rate of burn injury while on LTOT was higher in Denmark than in Sweden; 170 (95% confidence interval [CI], 126-225) vs 85 (95% CI, 44-148) per 100,000 person-years; rate ratio 2.0 (95% CI, 1.0-4.1). The risk remained higher after adjustment for gender, age, and diagnosis in multivariate Cox regression, hazard ratio 1.8 (95% CI, 1.0-3.5). Thirty-day mortality after burn injury was 8% in both countries.CONCLUSION: Compared to Sweden, the rate of burn injury was twice as high in Denmark where smoking is not a contraindication for prescribing LTOT.

BackgroundObese patients can develop a large lower abdominal panniculus (worsened by significant weight loss). Patients with advanced chronic kidney disease (CKD) affected by this obesity-related sequela are not infrequently declined for kidney transplantation because of the high risk for serious wound-healing complications. We hypothesized that pretransplant panniculectomy in these patients would (1) render them transplant candidates, and (2) result in low posttransplant wound-complication rates.MethodsIn a pilot study, adult patients with CKD who had a high-risk panniculus as the only absolute contraindication to kidney transplantation subsequently were referred to a plastic surgeon to undergo a panniculectomy in order to become transplant candidates. We analyzed the effect of panniculectomy on (1) transplant candidacy and (2) wait list and transplant outcomes (04/2008-06/2014).ResultsOverall, 36 patients had panniculectomy (median prior weight loss, 38 kg); all were wait-listed with these outcomes: (1) 22 (62%) patients were transplanted; (2) 7 (19%) remain listed; and (3) 7 (19%) were removed from the wait list. Survival after panniculectomy was greater for those transplanted versus not transplanted (at 5 years, 95% vs 35%, respectively; P = .002). For the 22 kidney recipients, posttransplant wound-complication rate was 5% (1 minor subcutaneous hematoma).ConclusionFor obese CKD patients with a high-risk abdominal panniculus, panniculectomy was highly effective in obtaining access to the transplant wait list and successful kidney transplantation. This approach is particularly pertinent for CKD patients because they are disproportionally affected by the obesity epidemic and because obese CKD patients already face multiple other barriers to transplantation.

IMPORTANCE: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation. OBJECTIVE: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded. INTERVENTIONS: Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori. RESULTS: Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; me

BackgroundObese patients can develop a large lower abdominal panniculus (worsened by significant weight loss). Patients with advanced chronic kidney disease (CKD) affected by this obesity-related sequela are not infrequently declined for kidney transplantation because of the high risk for serious wound-healing complications. We hypothesized that pretransplant panniculectomy in these patients would (1) render them transplant candidates, and (2) result in low posttransplant wound-complication rates.MethodsIn a pilot study, adult patients with CKD who had a high-risk panniculus as the only absolute contraindication to kidney transplantation subsequently were referred to a plastic surgeon to undergo a panniculectomy in order to become transplant candidates. We analyzed the effect of panniculectomy on (1) transplant candidacy and (2) wait list and transplant outcomes (04/2008-06/2014).ResultsOverall, 36 patients had panniculectomy (median prior weight loss, 38 kg); all were wait-listed with these outcomes: (1) 22 (62%) patients were transplanted; (2) 7 (19%) remain listed; and (3) 7 (19%) were removed from the wait list. Survival after panniculectomy was greater for those transplanted versus not transplanted (at 5 years, 95% vs 35%, respectively; P = .002). For the 22 kidney recipients, posttransplant wound-complication rate was 5% (1 minor subcutaneous hematoma).ConclusionFor obese CKD patients with a high-risk abdominal panniculus, panniculectomy was highly effective in obtaining access to the transplant wait list and successful kidney transplantation. This approach is particularly pertinent for CKD patients because they are disproportionally affected by the obesity epidemic and because obese CKD patients already face multiple other barriers to transplantation.

IMPORTANCE: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation. OBJECTIVE: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded. INTERVENTIONS: Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori. RESULTS: Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; me

Diabetes mellitus, heart failure (HF), and chronic kidney disease are common comorbidities, but overall use and safety of antihyperglycemic medications (AHMs) among patients with these comorbidities are poorly understood. Using Get With the Guidelines-Heart Failure and linked Medicare Part D data, we assessed AHM use within 90 days of hospital discharge among HF patients with diabetes mellitus discharged from Get With the Guidelines-Heart Failure hospitals between January 1, 2006, and October 1, 2011. We further summarized use by renal function and assessed renal contraindicated AHM use for patients with estimated glomerular filtration rate <30 mL/min/1.73m(2). Among 8791 patients meeting inclusion criteria, the median age was 77 (interquartile range 71-83), 62.3% were female, median body mass index was 29.7 (interquartile range 25.5-35.3), median hemoglobin A1c was 6.8 (interquartile range 6.2-7.8), and 34% had ejection fraction <40%. 74.9% of patients filled a prescription for an AHM, with insulin (39.5%), sulfonylureas (32.4%), and metformin (17%) being the most commonly used AHMs. Insulin use was higher and sulfonylurea/metformin use was lower among patients with lower renal function classes. Among 1512 patients with estimated glomerular filtration rate <30 mL/min/1.73m(2), 35.4% filled prescriptions for renal contraindicated AHMs per prescribing information, though there was a trend toward lower renal contraindicated AHM use over time (Cochran-Mantel-Haenszel row-mean score test P=0.048). Although use of other AHMs was low overall, thiazolidinediones were used in 6.6% of HF patients, and dipeptidyl peptidase-4 inhibitors were used in 5.1%, with trends for decreasing thiazolidinedione use and increased dipeptidyl peptidase-4 inhibitor use over time (P<0.001). Treatment of diabetes mellitus in patients with HF and chronic kidney disease is complex, and these patients are commonly treated with renal contraindicated AHMs, including over 6% receiving a t

Bakgrund Ventilatorbehandling kan orsaka lidande i form av bland annat Ventilator Associerad Pneumoni (VAP) och delirium. Att avsluta behandlingen för tidigt kan också orsaka lidande och därför är tydliga kriterier för att verifiera urträning och extubation, borttagande av ventilatorn och endotrakealtuben är viktiga aspekter i vården och omvårdnaden av patienten. Syfte Syftet med studien var att identifiera kriterier för att verifiera lyckade eller misslyckade urträningar och extubationer hos intensivvårdspatienter och att undersöka vilka bedömningsprotokoll för detta som används. Metod Metoden har varit en (deskriptiv) litteraturöversikt med systematisk ansats. Sökning har gjorts i databasen PubMed. Vid sökningen hittades 627 artiklar och av dessa inkluderas 17 artiklar i studien. Resultat Resultatet visar att det finns flera kriterier för att verifiera lyckade eller misslyckade urträningar och extubationer, men de mest uttalade kriterierna var, hemodynamisk status, inställda/uppmätta ventilatorvärden, blodgasvärden, det mentala/neurologiska tillståndet hos patienten och spontant andningstest (SBT). Slutsats Kriterier och dess protokoll är viktiga redskap för vårdpersonalen för att avgöra när det är dags att börja urträning och förbereda för extubation av den ventilatorbehandlade patienten., Background Mechanical ventilation can cause suffering in the form of, among other things Ventilator Associated Pneumonia (VAP) and delirium. Stopping treatment too early may also cause suffering and therefore clear criteria to assess extubation withdrawal and weaning of the ventilator are important aspects in the care and nursing of the patient. Purpose The purpose of the study was to identify criteria for verifying successful or unsuccessful weaning and extubations in ICU patients and to investigate assessment protocol. Method The method has been a descriptive literature review with a systematic approach. Conclusion The result shows that there are several criteria to verify successful or unsuccessful weanings and extubations, but the most explicit criteria were - hemodynamic status, set / measured values for the mechanical ventilations, blood gas status, mental / neurological state of the patient and spontaneous breathing test (SBT). Criteria and subsequent protocols are important tools for caregivers to determine when it is time to start weaning and prepare for extubation.

Management of hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) is complex and requires an understanding of multiple therapeutic options. PVT is present in 10%-40% of HCC at the time of diagnosis, and is an adverse prognostic factor. Management options are limited, as transplantation is generally contraindicated, and surgical resection is only rarely performed in select centers. Systemic medical therapy with sorafenib has been shown to modestly prolong survival. Transarterial chemoembolization has been performed in select cases but has shown a high incidence of complications. Emerging data on treatment of PVT with Y-90 radioembolization suggest that this modality is well-tolerated and associated with favorable overall survival. Current society guidelines do not yet specifically recommend radioembolization for patients with PVT, but this may change with the development of newer staging systems and treatment algorithms. In this comprehensive literature review, we present current and available management options with the relative advantages, disadvantages and contraindications of these treatment options with summarized data on overall survival.

Bakgrund Ventilatorbehandling kan orsaka lidande i form av bland annat Ventilator Associerad Pneumoni (VAP) och delirium. Att avsluta behandlingen för tidigt kan också orsaka lidande och därför är tydliga kriterier för att verifiera urträning och extubation, borttagande av ventilatorn och endotrakealtuben är viktiga aspekter i vården och omvårdnaden av patienten. Syfte Syftet med studien var att identifiera kriterier för att verifiera lyckade eller misslyckade urträningar och extubationer hos intensivvårdspatienter och att undersöka vilka bedömningsprotokoll för detta som används. Metod Metoden har varit en (deskriptiv) litteraturöversikt med systematisk ansats. Sökning har gjorts i databasen PubMed. Vid sökningen hittades 627 artiklar och av dessa inkluderas 17 artiklar i studien. Resultat Resultatet visar att det finns flera kriterier för att verifiera lyckade eller misslyckade urträningar och extubationer, men de mest uttalade kriterierna var, hemodynamisk status, inställda/uppmätta ventilatorvärden, blodgasvärden, det mentala/neurologiska tillståndet hos patienten och spontant andningstest (SBT). Slutsats Kriterier och dess protokoll är viktiga redskap för vårdpersonalen för att avgöra när det är dags att börja urträning och förbereda för extubation av den ventilatorbehandlade patienten., Background Mechanical ventilation can cause suffering in the form of, among other things Ventilator Associated Pneumonia (VAP) and delirium. Stopping treatment too early may also cause suffering and therefore clear criteria to assess extubation withdrawal and weaning of the ventilator are important aspects in the care and nursing of the patient. Purpose The purpose of the study was to identify criteria for verifying successful or unsuccessful weaning and extubations in ICU patients and to investigate assessment protocol. Method The method has been a descriptive literature review with a systematic approach. Conclusion The result shows that there are several criteria to verify successful or unsuccessful weanings and extubations, but the most explicit criteria were - hemodynamic status, set / measured values for the mechanical ventilations, blood gas status, mental / neurological state of the patient and spontaneous breathing test (SBT). Criteria and subsequent protocols are important tools for caregivers to determine when it is time to start weaning and prepare for extubation.

Infusion therapy is an important component of treatment of almost all kinds of shock and intensive care. In the article the basic problems of choice of solutions for infusion therapy are discussed. The emphasis is on the use of hydroxyethyl starch (HES ) solutions. The authors provide a brief historical data regarding solutions for infusion therapy. The effect of HES solutions molecular weight on the adverse effects of infusion therapy comparing to crystalloid solutions are considered, various data on the safety and efficacy of HES compared to albumin and other semi-synthetic colloids are reviewed. Also the latest recommendations on the use of these solutions as a part of infusion therapy are provided., Инфузионная терапия является важным компонентом лечения практически всех видов шока и вообще интенсивной терапии. В статье обсуждаются основные проблемы выбора растворов для инфузионной терапии. Акцент делается на применении растворов гидроксиэтилкрахмалов (ГЭК). Авторы приводят краткие исторические данные касательно растворов для инфузионной терапии. Рассматривают влияние молекулярного веса растворов ГЭК на неблагоприятные эффекты инфузионной терапии, проводят сравнение ГЭК с кристаллоидными растворами, приводят различные данные о безопасности и эффективности ГЭК по сравнению с альбумином и другими полусинтетическими коллоидами. Также приводятся последние рекомендации по применению этих растворов в составе инфузионной терапии., Iнфузiйна терапiя є важливим компонентом лiкування практично всiх видiв шоку i взагалi iнтенсивної терапiї. У статтi обговорюються основнi проблеми вибору розчинiв для iнфузiйної терапiї. Акцент робиться на застосуваннi розчинiв гiдроксиетилкрохмалiв (ГЕК). Автори наводять короткi iсторичнi данi щодо розчинiв для iнфузiйної терапiї. Розглядають вплив молекулярної ваги розчинiв ГЕК на несприятливi ефекти iнфузiйної терапiї, проводять порiвняння ГЕК з кристалоїдними розчинами, наводять рiзнi данi про безпеку та ефективнiсть ГЕК в порiвняннi з альбумiном та iншими напiвсинтетичними колоїдами. Також наводяться останнi рекомендацiї щодо застосування цих розчинiв у складi iнфузiйної терапiї.

Background and objectivesNational guidelines have recommended against codeine use in children, but little is known about prescribing patterns in the United States. Our objectives were to assess changes over time in pediatric codeine prescription rates in emergency departments nationally and to determine factors associated with codeine prescription.MethodsWe performed a serial cross-sectional analysis (2001-2010) of emergency department visits for patients ages 3 to 17 years in the nationally representative National Hospital Ambulatory Medical Care Survey. We determined survey-weighted annual rates of codeine prescriptions and tested for linear trends over time. We used multivariate logistic regression to identify characteristics associated with codeine prescription and interrupted time-series analysis to assess changes in prescriptions for upper respiratory infection (URI) or cough associated with two 2006 national guidelines recommending against its use for these indications.ResultsThe proportion of visits (N = 189 million) with codeine prescription decreased from 3.7% to 2.9% during the study period (P = .008). Odds of codeine prescription were higher for children ages 8 to 12 years (odds ratio [OR], 1.42; 95% confidence interval [1.21-1.67]) and among providers outside the northeast. Odds were lower for children who were non-Hispanic black (OR, 0.67 [0.56-0.8]) or with Medicaid (OR, 0.84 [0.71-0.98]). The 2006 guidelines were not associated with a decline in codeine prescriptions for cough or URI visits.ConclusionsAlthough there was a small decline in codeine prescription over 10 years, use for cough or URI did not decline after national guidelines recommending against its use. More effective interventions are needed to prevent codeine prescription to children.

Objective. External cephalic version (ECV) is a safe and effective intervention that can prevent breech delivery, thus reducing the need for cesarean delivery. It is recommended in national guidelines. These guidelines also mention contraindications for ECV, and thereby restrict the application of ECV. We assessed whether the formulation of these contraindications in guidelines are based on empiric data. Design. Systematic review. Population. Pregnant women with a singleton breech presentation from 34 weeks. Methods. We searched the National Guideline Clearinghouse, the Cochrane Central Register of Controlled Trials, MEDLINE (1953-2009), EMBASE (1980-2009), TRIP database (until 2011), NHS (National Health Services, until 2011), Diseases database (until 2011) and NICE guidelines (until 2011) for existing guidelines on ECV and studied the reproducibility of the contraindications stated in the guidelines. Furthermore, we systematically reviewed the literature for contraindications and evidence on these contraindications. Main outcome measures. Contraindications of ECV. Results. We found five guidelines mentioning 18 contraindications, varying from five to 13 per guideline. The contraindications were not reproducible between the guidelines with oligohydramnios as the only contraindication mentioned in all guidelines. The literature search yielded 60 studies reporting on 39 different contraindications, of which we could only assess evidence of six of them. Conclusion. The present study shows that there is no general consensus on the eligibility of patients for ECV. Therefore we propose to limit contraindications for ECV to clear empirical evidence or to those with a clear pathophysiological relevance. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Objective. External cephalic version (ECV) is a safe and effective intervention that can prevent breech delivery, thus reducing the need for cesarean delivery. It is recommended in national guidelines. These guidelines also mention contraindications for ECV, and thereby restrict the application of ECV. We assessed whether the formulation of these contraindications in guidelines are based on empiric data. Design. Systematic review. Population. Pregnant women with a singleton breech presentation from 34 weeks. Methods. We searched the National Guideline Clearinghouse, the Cochrane Central Register of Controlled Trials, MEDLINE (1953–2009), EMBASE (1980–2009), TRIP database (until 2011), NHS (National Health Services, until 2011), Diseases database (until 2011) and NICE guidelines (until 2011) for existing guidelines on ECV and studied the reproducibility of the contraindications stated in the guidelines. Furthermore, we systematically reviewed the literature for contraindications and evidence on these contraindications. Main outcome measures. Contraindications of ECV. Results. We found five guidelines mentioning 18 contraindications, varying from five to 13 per guideline. The contraindications were not reproducible between the guidelines with oligohydramnios as the only contraindication mentioned in all guidelines. The literature search yielded 60 studies reporting on 39 different contraindications, of which we could only assess evidence of six of them. Conclusion. The present study shows that there is no general consensus on the eligibility of patients for ECV. Therefore we propose to limit contraindications for ECV to clear empirical evidence or to those with a clear pathophysiological relevance.

Objective. External cephalic version (ECV) is a safe and effective intervention that can prevent breech delivery, thus reducing the need for cesarean delivery. It is recommended in national guidelines. These guidelines also mention contraindications for ECV, and thereby restrict the application of ECV. We assessed whether the formulation of these contraindications in guidelines are based on empiric data. Design. Systematic review. Population. Pregnant women with a singleton breech presentation from 34 weeks. Methods. We searched the National Guideline Clearinghouse, the Cochrane Central Register of Controlled Trials, MEDLINE (1953–2009), EMBASE (1980–2009), TRIP database (until 2011), NHS (National Health Services, until 2011), Diseases database (until 2011) and NICE guidelines (until 2011) for existing guidelines on ECV and studied the reproducibility of the contraindications stated in the guidelines. Furthermore, we systematically reviewed the literature for contraindications and evidence on these contraindications. Main outcome measures. Contraindications of ECV. Results. We found five guidelines mentioning 18 contraindications, varying from five to 13 per guideline. The contraindications were not reproducible between the guidelines with oligohydramnios as the only contraindication mentioned in all guidelines. The literature search yielded 60 studies reporting on 39 different contraindications, of which we could only assess evidence of six of them. Conclusion. The present study shows that there is no general consensus on the eligibility of patients for ECV. Therefore we propose to limit contraindications for ECV to clear empirical evidence or to those with a clear pathophysiological relevance.

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting. © Georg Thieme Verlag KG stuttgart .New York., SCOPUS: ar.j, info:eu-repo/semantics/published

Background and objectivesFamily physicians and obstetrician-gynecologists provide much of contraceptive care in the United States and have a shared goal in preventing unintended pregnancy among patients. We assessed their competency to offer women contraceptives of the highest efficacy levels.MethodsWe conducted a national probability survey of family physicians and obstetrician-gynecologists (n=1,192). We measured counseling and provision practices of intrauterine contraception and used multivariable regression analysis to evaluate the importance of evidence-based knowledge to contraceptive care.ResultsFamily physicians reported seeing fewer contraceptive patients per week than did obstetrician-gynecologists and were less likely to report sufficient time for counseling. While 95% of family physicians believed patients were receptive to learning about intrauterine contraception, fewer than half offered counseling or the method. Only half were trained to competence to offer intrauterine contraception, while virtually all obstetrician-gynecologists were. Both family physicians and obstetrician-gynecologists were unlikely to have adequate knowledge of the women who would be good candidates for intrauterine contraception-as gauged by the Centers for Disease Control and Prevention Medical Eligibility Criteria for contraception-and consequently did not offer the method to a wide range of eligible patients.ConclusionsMost family physicians providing contraceptive care were not offering methods with top-tier effectiveness, although they reported interest in updating contraceptive skills through training. Obstetrician-gynecologists had technical skills to offer intrauterine contraception but still required education on patient selection. Greater hands-on training opportunities for family physicians, and complementary education on eligible method candidates for obstetrician-gynecologists, can increase access to intrauterine contraception by women seeking contraceptive care.