Reinterventions in Patients with Claudication and Chronic Limb Threatening Ischemia.

BACKGROUND: Patients with peripheral artery disease (PAD) present with claudication or chronic limb threatening ischemia (CLTI). CLTI patients have a more advanced stage of atherosclerosis and increased comorbidities compared to claudicants, and are at an elevated risk of major amputation and mortality after lower extremity revascularization (LER). However, the frequency of reinterventions for claudication and CLTI have not been compared. Our hypothesis is that patients with CLTI undergo more frequent reinterventions to prevent major amputation. METHODS: A single-center retrospective chart review of consecutive patients undergoing lower extremity revascularization (LER) for PAD in 2013-2015 was performed. Patients were stratified based on indication for revascularization into claudication or CLTI. Patient characteristics, outcomes, and reinterventions were compared between the 2 groups. RESULTS: There were 826 patients undergoing LER and 44% (N = 361) had CLTI. Patients treated for CLTI were more likely to be smokers (P < 0.001), to have diabetes (P< 0.001), chronic renal insufficiency (P< 0.001), end stage renal disease (P< 0.001), and cardiac disease (P< 0.001). CLTI patients were less likely to be on optimal medical management as reflected by decreased rate of aspirin (P< 0.001), ADP receptor/P2Y12 inhibitors (P< 0.001), and statins (P< 0.001) compared to patients with claudication. Patients with CLTI had significantly higher major amputation (3.7% vs. 0.2%, P< 0.001) and mortality (1.4% vs. 0.2%, P = 0.092) at 30 days. At long-term follow up, patients with CLTI had higher rates of major amputation (15.5% vs. 1.3%, P < 0.001) and mortality (37.1% vs. 18.1%, P < 0.001) compared to patients with claudication. There was a significant difference in mean follow-up time between the 2 cohorts (claudication: 3.7 ± 1.5 years versus CLTI: 2.6 ± 1.8 years, P < 0.001). There was no significant difference in the ipsilateral reintervention rate between the 2 groups (claudication: 39.6% vs. CLTI: 42.7%, P = 0.37) or the mean number of ipsilateral reinterventions (claudication: 2.0 ± 1.6 vs. CLTI: 2.0 ± 1.7). However, after adjusting for follow-up time, the mean number of reinterventions per year was significantly higher for CLTI patients compared to patients with claudication (1.4 ± 2.2 vs. .6 ± 0.7 intervention per year, P < 0.001). CONCLUSIONS: Patients undergoing LER for CLTI undergo more frequent reinterventions over time compared to patients treated for claudication. Research on reinterventions after LER should include reporting of the frequency of reintervention adjusted for the follow up period in addition to the reintervention rate defined as the percentage of patients undergoing reintervention.

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

Analysis of prognostic factors for postoperative complications and reinterventions after open surgical repair and endovascular aneurysm repair in patients with abdominal aortic aneurysm.

OBJECTIVE: A definitive treatment for patients with abdominal aortic aneurysm considering age and comorbidities has not been identified. In the present study, we retrospectively validated treatment outcomes in Japanese patients and proposed the treatment strategy of open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: We retrospectively analyzed data for patients undergoing EVAR or OSR between 2006 and 2017. Patients with ruptured abdominal aortic aneurysm were excluded. We examined post-operative complications, operative mortality, re-intervention and prognosis. RESULTS: Throughout the study period, 405 patients underwent EVAR and 176 patients underwent OSR. The percentage of patients with post-operative complications was 35.8% in the OSR group, compared with 13.1% in the EVAR group (P < 0.01). The operative mortality rate was 0.49% in the EVAR group and 0.57% in the OSR group (P = 1.00). With a multivariate analysis, age, hemodialysis, modified Frailty Index (mFI), and OSR were risk factors for post-operative complications. The 5-year re-intervention free survival rate was 63.0 % with hostile neck EVAR compared with 83.1 % with favorable neck EVAR and 86.1 % with OSR group (P < 0.01). With a multivariate analysis, hemodialysis, mFI, and hostile neck EVAR were risk factors for re-intervention. The 5-year overall survival rate was 51.9 % with hostile neck EVAR compared with 73.2 % with favorable neck EVAR and 79.0 % with OSR group (P < 0.01). With a multivariate analysis, age, mFI, and hostile neck EVAR were poor prognostic factors. CONCLUSION: Age, mFI, hemodialysis and hostile neck anatomy are useful predictors of post-operative complications, re-intervention and overall survival, and could be useful for informing treatment selection between OSR and EVAR.

Prognostic role of alpha-fetoprotein in patients with hepatocellular carcinoma treated with repeat transarterial chemoembolisation.

BACKGROUND: Repeat transarterial chemoembolisation (rTACE) is often required for hepatocellular carcinoma (HCC) to achieve disease control, however, current practice guidelines regarding treatment allocation vary significantly. This study aims to identify key factors associated with patient survival following rTACE to facilitate treatment allocation and prognostic discussion. METHOD: Patients with HCC undergoing rTACE at six Australian tertiary centers from 2009 to 2014 were included. Variables encompassing clinical, tumour, treatment type and response factors were analysed against the primary outcome of overall survival. Univariate analysis and multivariate Cox regression modelling were used to identify factors pre- and post-TACE therapy significantly associated with survival. RESULTS: Total of 292 consecutive patients underwent rTACE with mainly Child Pugh A cirrhosis (61%) and BCLC stage A (57%) disease. Median overall survival (OS) was 30 months (IQR 15.2-50.2) from initial TACE. On multivariate analysis greater tumour number (p = 0.02), higher serum bilirubin (p = 0.007) post initial TACE, and hepatic decompensation (p = 0.001) post second TACE were associated with reduced survival. Patients with serum AFP ≥ 200 ng/ml following initial TACE had lower survival (p = 0.001), compared to patients with serum AFP level that remained < 200 ng/ml post-initial TACE, with an overall survival of 19.4 months versus 34.7 months (p = 0.0001) respectively. CONCLUSION: Serum AFP level following initial treatment in patients undergoing repeat TACE for HCC is a simple and useful clinical prognostic marker. Moreover, it has the potential to facilitate appropriate patient selection for rTACE particularly when used in conjunction with baseline tumour burden and severity of hepatic dysfunction post-initial TACE.

Geriatric nutritional risk index as a useful prognostic factor in second allogeneic hematopoietic stem cell transplantation.

Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2 years after second allo-HSCT: 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2 years after second allo-HSCT decreased according to the score: 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P < 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.

The Reintervention Index: A New Outcome Measure for Comparative Effectiveness of Lower Extremity Revascularization.

BACKGROUND: Reinterventions after lower extremity revascularization (LER) are common. Current outcome measures assessing durability of revascularization rely on freedom from reintervention but do not account for the frequency of repeated LER. The aim of this study is to compare the reintervention index, defined as the mean number of repeat LER, after open and endovascular revascularization. We hypothesized that endovascular procedures have reduced durability and increased frequency of reinterventions. METHODS: A retrospective review of the charts of consecutive patients undergoing LER for peripheral artery disease (PAD) in 2013-2014 by multiple specialties in a tertiary care center was performed. Patients were divided into open and endovascular groups based on the first LER procedure performed during the study period. Patient characteristics and outcomes were compared between the 2 groups. Multivariable regression was performed to determine factors associated with reintervention. RESULTS: There were 367 patients (Endo = 316, Open = 51). A total of 211 patients underwent 497 reinterventions (reintervention rate = 57.5%, reintervention index = 2.35 ± 2.02 procedures [range 1-11]). Patients in the open group were more likely to be smokers (P = 0.018) and to have prior open LER (P = 0.003), while patients in the endovascular group were older (P < 0.001) and more likely to have cardiovascular comorbidities. On follow-up, there was no difference in overall or ipsilateral reintervention rates or reintervention indices between endovascular and open LER. Major amputation was significantly higher after open LER (19.61% vs. 8.54%, P = 0.013) but there was no difference in survival (P = 0.448). Multivariable analysis did not show a significant relationship between type of procedure and reintervention. CONCLUSIONS: The reintervention index provides a measure to assess the frequency of repeat LER. Patients with PAD, in this study, are afflicted with similar extent of reinterventions after open and endovascular LER.

Repeat procedure is a new independent predictor of complications of atrial fibrillation ablation.

AIMS: Atrial fibrillation (AF) ablation has made huge progress with respect to innovation, efficacy, and safety, however, complications are still present. Recent studies examined various predictors of complications. However, limited data exist regarding the role of a repeat procedure. Our aim was the prospective evaluation of the incidence and predictors of complications related to AF ablation procedures in consecutive patients, including repeat procedures. METHODS AND RESULTS: All ablation procedures for AF between January 2013 and December 2015 were analysed in our electrophysiology laboratory. During the study period 1243 procedures were analysed [394 female, median age 62 (55-69)]. Overall complication rate was 6.84%, major complication rate was 2.82%. Major complications were the following: 18 pericardial tamponades; 5 pseudoaneurysms; 1 arteriovenous fistula; 6 thromboembolic cerebrovascular events; 3 pulmonary vein stenosis; and 2 atrioventricular blocks. No atrio-oesophageal fistula or procedure related death occurred. Univariate analysis for overall complications showed that age ≥ 65 years (P = 0.0231), female gender (P = 0.0438), hypertension (P = 0.0488), CHA2DS2-VASc score ≥ 2 (P = 0.0156), and previous AF ablation procedure (P < 0.0001) is associated with higher risk for adverse events. Multivariate analysis showed that the only independent predictor of overall complications was previous AF ablation procedure (P < 0.0001). Similarly, the only predictor of major complications was previous AF ablation procedure (P < 0.0001). CONCLUSION: Incidence of complications associated with AF ablation in our high volume electrophysiology laboratory is similar to other cohorts. The only independent predictor of complications was previous AF ablation procedure in our series.

Recommendations for Prevention of Drug Re-Exposure in Toxic Epidermal Necrolysis

Drug re-exposure resulting in Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is a rare phenomenon and has scarcely been reported. With an aging population, polypharmacy, and a lack of a unified electronic medical record, standard recommendations to prevent or minimize the risk of re-exposure are necessary. We identified five patients, with diagnosis confirmed SJS/TEN, and determined the clinical characteristics and contributing risk factors leading to re-exposure. Polypharmacy, multiple prescribers, advanced age, medical illiteracy, retention of discontinued medications and self-prescribing all contributed to re-exposure in this cohort of patients. This case series demonstrates the potentially deadly effect of drug re-exposure, and the need for both streamlined and integrated medication allergy documentation systems. J Drugs Dermatol. 2019;18(10):1049-1052.

Salvage treatment using carbon ion radiation in patients with locoregionally recurrent nasopharyngeal carcinoma: Initial results.

BACKGROUND: Reirradiation for locoregionally recurrent nasopharyngeal carcinoma (NPC) after a definitive dose of radiotherapy (RT) is challenging and usually associated with severe toxicities. Intensity-modulated carbon ion RT (IMCT) offers physical/biologic advantages over photon-based intensity-modulated RT. Herein, the authors report their initial experience of IMCT in previously irradiated patients with locoregionally recurrent NPC. METHODS: Patients with locoregionally recurrent, poorly differentiated or undifferentiated NPC who underwent salvage therapy with IMCT at the Shanghai Proton and Heavy Ion Center between May 2015 and August 2017 were included in the current study. The IMCT doses were 50 to 66 Gray equivalent (GyE) (2.0-3.0 GyE/daily fraction), delivered via raster scanning technology. The 1-year overall survival, disease-specific survival, progression-free survival (PFS), local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival were calculated. Univariate and multivariate analyses of PFS were performed to identify possible predictive factors. RESULTS: Among the 75 patients included, 4 patients, 14 patients, 29 patients, and 28 patients, respectively, had recurrent American Joint Committee on Cancer stage I, stage II, stage III, and stage IVA/B disease. With a median follow-up of 15.4 months (range, 2.6-29.7 months), the 1-year overall survival, disease-specific survival, PFS, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival rates were 98.1%, 98.1%, 82.2%, 86.6%, 97.9%, and 96.2%, respectively. A higher fraction size of 3 GyE (vs <3 GyE) or a higher biological equivalent dose significantly improved the PFS rate on univariate analysis, but not on multivariate analysis. No patient developed acute toxicity of grade ≥2 during IMCT. Late treatment-induced severe (grade 3 or 4) toxicities were infrequent, but included mucosal necrosis (9.3%), xerostomia (1.3%), and temporal lobe necrosis (1.3%). CONCLUSIONS: This initial experience in the first 75 patients with locoregionally recurrent NPC was encouraging. Carbon ion RT could provide promising survival rates with infrequent severe toxicities for patients with locoregionally recurrent NPC. Cancer 2018;124:2427-37. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Multiple red blood cell transfusions and iron overload in very low birthweight infants.

BACKGROUND AND OBJECTIVES: To estimate the risk of iron overload in very low birthweight (VLBW) infants who receive more than two red blood cell (RBC) transfusions, in comparison with those who receive two or less during their hospital stay. MATERIALS AND METHODS: Prospective open cohort study in VLBW infants with >2 (exposed) and ≤2 (non-exposed) RBC transfusions. Ferritin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at birth and after each RBC transfusion. The incidence of iron overload was determined. Risk factors were analysed using a logistic regression model. RBC transfusion volume correlations with ferritin, ALT and AST were calculated with Spearman's rank correlation coefficient, as well as correlations between ferritin and aminotransferases. RESULTS: A total of 63 patients were enrolled, 18 of which were exposed and 45 non-exposed. Twelve patients developed severe iron overload, eight exposed (44·5%) vs. four (8·8%) non-exposed (RR: 5, 95% CI: 1·7-14·6). Multivariate analysis showed that the number of transfusions increased the risk of iron overload (OR: 2·07, 95% CI: 1·36-2·14) while a higher one-minute Apgar score was associated with a lower risk (OR: 0·56, 95% CI: 0·32-0·99). Severe iron overload mainly occurred with a transfusion volume higher than 120 ml/kg. There was a positive correlation between ferritin and transfusion (r = 0·53; P < 0·001). CONCLUSION: There was a higher risk of iron overload in exposed infants in comparison with non-exposed infants. Severe iron overload in VLBW infants may occur with a total transfusion volume >120 ml/kg.

Successful Retreatment of Chronic HCV Genotype-1 Infection With Ledipasvir and Sofosbuvir After Initial Short Course Therapy With Direct-Acting Antiviral Regimens.

BACKGROUND: The optimal retreatment strategy for chronic hepatitis C virus (HCV) patients who fail directly-acting antiviral agent (DAA)-based treatment is unknown. In this study, we assessed the efficacy and safety of ledipasvir (LDV) and sofosbuvir (SOF) for 12 weeks in HCV genotype-1 (GT-1) patients who failed LDV/SOF-containing therapy. METHODS: In this single-center, open-label, phase 2a trial, 34 participants with HCV (GT-1) and early-stage liver fibrosis who previously failed 4-6 weeks of LDV/SOF with GS-9669 and/or GS-9451 received LDV/SOF for 12 weeks. The primary endpoint was HCV viral load below the lower limit of quantification 12 weeks after completion of therapy (sustained virological response [SVR]12). Deep sequencing of the NS3, NS5A, and NS5B regions were performed at baseline, at initial relapse, prior to retreatment, and at second relapse with Illumina next-generation sequencing technology. RESULTS: Thirty-two of 34 enrolled participants completed therapy. Two patients withdrew after day 0. Participants were predominantly male and black, with median baseline HCV viral load of 1.3 × 10(6) IU/mL and Metavir fibrosis stage 1 and genotype-1a. Median time from relapse to retreatment was 22 weeks. Prior to retreatment, 29 patients (85%) had NS5A-resistant variants. The SVR12 rate was 91% (31/34; intention to treat, ITT) after retreatment. One patient relapsed. CONCLUSIONS: In patients who previously failed short-course combination DAA therapy, we demonstrate a high SVR rate in response to 12 weeks of LDV/SOF, even for patients with NS5A resistance-associated variants. CLINICAL TRIALS REGISTRATION: NCT01805882.

Safety and Feasibility of Repeatable Hepatic Vascular Isolation Chemotherapy: A Pilot Study.

BACKGROUND: The authors herein describe a novel method of repeatable hepatic isolation using an implantable access system allowing simultaneous control of hepatic arterial and portal flows by multiple endovascular catheters. PURPOSE: The aim of this study was to assess the feasibility and safety of the system and to compress standard intravenous chemotherapy into 4 weeks of targeted intra-arterial delivery. METHODS: An arterial access system was implanted to the axillary artery via an anastomosis. Infusions of oxaliplatin were performed biweekly for 4 weeks, using balloon catheters to achieve hepatic isolation and segmental selectivity for 20-25 min. Fifty-seven treatments under general anesthetic were performed in ten patients with inoperable chemotherapy-refractory metastatic colorectal cancer. Systemic, intrahepatic, and hepatic venous pressures were recorded to assess vascular isolation, and platinum levels were measured to assess chemotherapy distribution. RESULTS: Pressure verified, multiple day-only hepatic vascular isolation infusions were achieved in nine of ten patients, with a single patient receiving multiple hepatic arterial infusions. Positron emission tomography-computed tomography (PET-CT) imaging confirmed partial response in three of ten patients and stable disease in three of ten patients. Systemic toxicity was minimal as all treatment-related gastrointestinal and neuropathic symptoms reported throughout the 4 weeks were grades 1-2. CONCLUSIONS: Intra-arterial chemotherapy infusions with hepatic vascular isolation can be achieved repeatedly with targeted selectivity and minimal complications using an implantable multicatheter access system. Oxaliplatin infusions over a 4-week period may achieve tumor response in selected patients in the salvage setting. The technique should be further assessed in a phase Ib/II study.

Reintubation in critically ill patients: procedural complications and implications for care.

INTRODUCTION: In critically ill patients, re-intubation is common and may be a high-risk procedure. Anticipating a difficult airway and identifying high-risk patients can allow time for life-saving preparation. Unfortunately, prospective studies have not compared the difficulty or complication rates associated with reintubation in this population. METHODS: We performed a secondary analysis of a prospective registry of in-hospital emergency airway management, focusing on patients that underwent multiple out-of-operating room intubations during a single hospitalization. Our main outcomes of interest were technical difficulty of intubation (number of attempts, need for adjuncts to direct laryngoscopy, best Cormack-Lehane grade and training level of final intubator) and the frequency of procedural complications (aspiration, arrhythmia, airway trauma, new hypotension, new hypoxia, esophageal intubation and cardiac arrest). We compared the cohort of reintubated patients to a matched cohort of singly intubated patients and compared each repeatedly intubated patient's first and last intubation. RESULTS: Our registry included 1053 patients, of which 151 patients (14%) were repeatedly intubated (median two per patient). Complications were significantly more common during last intubation compared to first (13% versus 5%, P = 0.02). The most common complications were hypotension (41%) and hypoxia (35%). These occurred despite no difference in any measure of technical difficultly across intubations. CONCLUSION: In this cohort of reintubated patients, clinically important procedural complications were significantly more common on last intubation compared to first.

Stereotactic body radiotherapy for head and neck cancer: an addition to the armamentarium against head and neck cancer.

In the recent years, stereotactic body radiation therapy (SBRT) has emerged as a potential therapy for head and neck malignancies. Although early results appear to be promising, serious acute and late effects have been observed, mainly in patients who have had prior external beam radiotherapy. This review will discuss the radiobiology of SBRT, clinical rationale and outcomes for SBRT in head and neck cancers and focus on the benefits and potential limitations in both de novo and re-irradiation settings.

Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes.

BACKGROUND: It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial. OBJECTIVES: To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 January 2015), searched reference lists of retrieved studies and contacted authors for further data. SELECTION CRITERIA: Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth. DATA COLLECTION AND ANALYSIS: We assessed trial quality and extracted data independently. MAIN RESULTS: We included 10 trials (a total of 4733 women and 5700 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, number needed to treat to benefit (NNTB) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNTB 30, 95% CI 19 to 79).Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) -75.79 g, 95% CI -117.63 to -33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.At early childhood follow-up, no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments. In women, for the two primary outcomes, there was no increase in infectious morbidity of chorioamnionitis or puerperal sepsis, and the likelihood of a caesarean birth was unchanged. AUTHORS' CONCLUSIONS: The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.

Safety of resuming tumour necrosis factor inhibitors in patients who developed tuberculosis as a complication of previous TNF inhibitors.

OBJECTIVES: There is no consensus on whether restarting TNF inhibitors (TNFis) after treatment of an active tuberculosis (TB) infection caused by previous TNFi exposure is safe. In this study we sought to determine the safety of resuming TNFis in patients following TB treatment. METHODS: The medical records of all patients (n = 683) that received TNFi treatment at a single rheumatology clinic between June 2003 and December 2012 were retrospectively reviewed. Among them, data from patients who developed active TB infection were collected and patient outcomes were evaluated for those who resumed TNFis after TB treatment. RESULTS: Of 683 patients, 13 patients developed an active TB infection during TNFi treatment (4 on etanercept, 4 on adalimumab and 5 on infliximab). The median duration of TNFi treatment before TB infection was 20 months. TNFi treatment was reinitiated in six patients: four within 2 months after TB treatment and two after completion of TB treatment. Four patients reinitiated with the same TNFi, whereas two patients started with another TNFi. During a mean follow-up of 30.6 months, all six patients successfully completed TB treatment with no TB infection relapses. CONCLUSION: Our results suggest that resuming TNFi therapy in patients following adequate TB treatment is safe, even before completion of TB treatment.

Pain in naïve and non-naïve subjects undergoing nonablative skin tightening dermatologic procedures: a nested randomized control trial.

BACKGROUND: Pain is expected during noninvasive skin tightening and can be anxiety provoking, especially for those who have not had prior treatments. OBJECTIVE: To compare pain reported by patients naïve to nonablative skin tightening energy devices with those who were not naive. METHODS AND MATERIALS: The non-naïve group at least three nonablative laser procedures or one nonablative skin tightening procedure, and the naïve group no previous treatments. Four sites at each of two anatomic locations (periorbital and midface or cheek) were treated in each subject with needle prick, pulsed dye laser, radiofrequency, and ultrasound with the order of the interventions randomized. All interventions except ultrasound were also applied to three abdominal sites. The difference in mean pain scores between naïve and nonnaïve subjects were averaged over the anatomic sites. RESULTS: Ten naïve and 10 non-naïve subjects completed study procedures. Mean pain scores ranged from 1.3 to 4.9. The mean for all naïve conditions was 2.3 ± 1.0, vs 2.2 ± 1.4 for non-naïve conditions. There was no overall difference according to group, device, or anatomic area. CONCLUSIONS: There was no significant difference in pain between naïve and non-naïve subjects undergoing cutaneous energy treatments. Individual devices may elicit more pain at specific anatomic locations.

Impact of early extubation and reintubation on the incidence of bronchopulmonary dysplasia in neonates.

OBJECTIVE: The objective of this study was to assess rates of bronchopulmonary dysplasia (BPD) and BPD/death in infants first extubated between day of life (DOL) 1 to 3 versus 4 to 7, 8+, and impact of reintubation. STUDY DESIGN: We included infants with gestational age ≤ 28 weeks, birth weight ≤ 1,000 g, and intubation on DOL 1. Proportional hazards regression modeled time to BPD and BPD/death, adjusting for potential confounders. RESULTS: Of 262 infants, 101 (38.55%), 41 (15.65%), and 120 (45.80%) were extubated between DOL 1 to 3, 4 to 7, and 8+, respectively. Extubation between DOL 4 to 7 and DOL 1 to 3 was associated with an increased hazard of developing BPD (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.0-2.8; p < 0.05). Extubation on DOL 8+ was associated with a significantly increased hazard compared with extubation between DOL 1 to 3 (HR, 16.9; 95% CI, 10.5-27.1; p < 0.0001) and DOL 4 to 7 (HR, 10.0; 95% CI, 6.1-16.3; p < 0.0001). Similar results were noted with BPD/death. Reintubation did not affect BPD and BPD/death. CONCLUSIONS: Delaying extubation beyond the first 3 and 7 days was associated with an increased risk of BPD and BPD/death. Reintubation did not impact outcomes.

Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes.

BACKGROUND: It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial. OBJECTIVES: To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), searched reference lists of retrieved studies and contacted authors for further data. SELECTION CRITERIA: Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth. DATA COLLECTION AND ANALYSIS: We assessed trial quality and extracted data independently. MAIN RESULTS: We included 10 trials (more than 4730 women and 5650 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, numbers needed to treat (NNT) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNT 30, 95% CI 19 to 79).Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) -75.79 g, 95% CI -117.63 to -33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.At early childhood follow-up no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments. AUTHORS' CONCLUSIONS: The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.