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Background and aims: Opioid agonist treatment (OAT) is currently the most effective treatment for people with opioid dependence. In most countries, however, access to the whole range of effective medications is restricted. This study aims to model the distribution of different OAT medications within a naturalistic and relatively unrestricted treatment setting (Zurich, Switzerland) over time, and to identify patient characteristics associated with each medication. Methods: We used generalized estimating equation analysis with data from the OAT register of Zurich and the Swiss register for heroin‐assisted treatment (HAT) to model and forecast the annual proportion of opioids applying exponential distributions until 2018 and patient characteristics between 1992 and 2015. Results: Data from 11 895 patients were included in the analysis. Methadone remains the mainstay of OAT, being prescribed to two‐thirds of patients. Following its approval, the proportion of HAT increased rapidly and is now constant at 12.16% [95% confidence interval (CI) = 11.15–13.17]. The initial increase of proportions of buprenorphine or slow‐release oral morphine (SROM) following their approval for OAT was slower. While in 2014 both medications had a proportion of 10.2% and 10.3%, respectively, our model predicts a further increase of SROM to 19.9% in 2018, with a ceiling level of 25.19% (21.40–28.98%) thereafter. SROM patients display characteristics similar to those treated with methadone; buprenorphine patients show the highest social integration; and HAT patients are the most homogeneous group, with highest mean age, most widespread injecting experience and lowest social integration. Conclusions: Based on data from Zurich, Switzerland from 1992 to 2015, there is no evidence for an excessive demand for a single medication in a naturalistic and liberal opioid agonist treatment setting. Rather, the specific patient characteristics associated with each medication underline the need for diversified treatment options for opioid dependence. [ABSTRACT FROM AUTHOR]

This is the case of an 18‐year‐old young adult woman with anorexia nervosa (AN) who presented to the emergency department with complications from AN and was found to be hyponatremic. The hyponatremia was prioritized and corrected with fluids on hospital day one. The consulting adolescent medicine team recommended the primary inpatient medical team initiate the malnutrition protocol. Nephrology recommended fluid restriction. Despite initiation of this protocol and emphasis on protocol adherence with the primary team, patient, and family, the hyponatremia recurred. Retrospectively, there were three factors that led to her recurrent hyponatremia: inconsistencies in protocol adherence across medical clinical providers, lack of knowledge regarding the importance of adherence to the malnutrition protocol, and suboptimal communication between medical clinical providers. A multidisciplinary team experienced in the care of patients with AN may enhance inpatient treatment of this condition. A multidisciplinary team experienced in AN will have a better understanding of the complexities of AN, skill in protocol implementation, understand the importance of protocol adherence, and be more likely to clearly communicate the plan of care to the patient/family. These skills can lead to improved care quality, decreased risk of adverse outcomes, and likely decreased medical costs. [ABSTRACT FROM AUTHOR]

Background: Greater occipital nerve block (GONB) is thought to be an effective treatment for acute migraine, though no randomized efficacy data have been published for this indication. We hypothesized that bilateral GONB with bupivacaine would provide greater rates of headache freedom than a sham injection among a population of emergency department (ED) patients who reported persistence of moderate or severe headache despite standard treatment with intravenous metoclopramide. Methods: This was a randomized clinical trial conducted in 2 urban EDs. Patients with acute migraine who reported persistence of a moderate or severe headache for at least 1 hour or longer after treatment with 10 mg of intravenous metoclopramide were randomized to bilateral GONB with a total of 6 mL of 0.5% bupivacaine or bilateral intradermal scalp injection with a total of 1 mL of 0.5% bupivacaine. The primary outcome was complete headache freedom 30 minutes after the injection. An important secondary outcome was sustained headache relief, defined as achieving a headache level of mild or none in the ED and maintaining a level of mild or none without the use of any additional headache medication for 48 hours. Results: Over a 31 month period, 76 patients were screened for participation and 28 were enrolled, of whom 15 received sham injection and 13 received GONB. This study was stopped before achieving the a priori sample size due to slow enrollment. The primary outcome – headache freedom at 30 minutes – was achieved by 0/15 (0%) of patients in the sham arm and 4/13 (31%) of patients in the GONB arm (95%CI for difference of 31%: 6, 56%, P = .035). The secondary outcome, sustained headache relief for 48 hours, was reported by 0/15 sham patients (0%) and 3/13 (23%) GONB patients (95% CI for difference of 23%: 0, 46%, P = .087). Reported side effects did not differ substantially between the groups. Conclusion: GONB may be an effective treatment for ED patients with acute migraine who continue to suffer from moderate or severe headache after administration of intravenous metoclopramide; however, this study was stopped prior to achieving the a priori sample size. [ABSTRACT FROM AUTHOR]

Abstract: Background: Evidence‐based medicine is the application of research findings to inform individual clinical decisions. There is a tension—both philosophical and practical—between the average result from a population study and the circumstances and needs of an individual patient. This personal account of “evidence‐based” trauma care illustrates and explores this tension. The case: The author, a keen athlete, describes her experience of a high‐impact cycle accident that led to limb fractures (which were diagnosed and treated according to evidence‐based guidelines) and also an occult injury to the cervical spine (which was not diagnosed at the time). Some evidence‐based guidelines are reviewed and applied to the case. The clinical record described the cycle accident as a “fall.” Initial assessment directed the clinicians' gaze to the obvious injuries, whose treatment was straightforward. On admission, the patient (aged 55 years at the time) was offered “falls prevention” via a guideline‐based checklist. Several months later, neurological sequelae indicated possible damage to the cervical spine. But the NICE Guideline recommending cervical spine imaging in cases of high‐impact trauma had not been considered—perhaps because the clinical narrative had been prematurely assigned to the script of “older person with fall.” Furthermore, the author, who was (appropriately) treated with neurosurgery, was surprised at the response of clinical colleagues, based on application of an irrelevant section of a guideline, that her cervical discectomy was “nonevidence based.” Nonsteroidal anti‐inflammatory drugs for postoperative pain were indicated in this patient even though they were not recommended for the average patient. Conclusion: As Sir John Grimley Evans' warned, we should avoid using evidence‐based guidelines in the manner of the fabled drunkard who searched under the lamp post for his key because that was where the light was, even though he knew he had lost his key somewhere else. [ABSTRACT FROM AUTHOR]

Objective: The aim of the current study was to assess the association between 3 different calcium channel blockers (CCBs) (nifedipine, amlodipine and felodipine) and gingival overgrowth in patients with a diagnosis of severe refractory hypertension. Methods: One hundred and sixty‐two patients with severe refractory hypertension, taking CCBs, were selected. Gingival overgrowth was graded and periodontal measurements were recorded (probing pocket depth, clinical attachment level, plaque index and bleeding on probing). Unconditional multivariable binary logistic regression analyses were performed to assess the association between CCB intake and gingival overgrowth after adjusting for potential confounders. Results: Of the 162 patients, 26 (16.0%) were current smokers and 101 (62.3%) were females. The mean age (SD) was 54.1 (8.5) years and the median age (range) 52.5 (39‐78) years. Gingival overgrowth was observed in 55 patients (34.0%). Nifedipine was the most common medication (35.2%; 57 of 162). The results of multiple binary logistic regression showed statistically significant associations between CCB intake (exposure) and gingival overgrowth (outcome) after adjusting for the variables treatment time with antihypertensive and plaque index. Patients with gingival overgrowth were 2.5 (odds ratio = 2.46; 95% confidence interval: 1.04‐5.82) and 4.0 (odds ratio = 3.90; 95% confidence interval: 1.47‐10.35) times more likely to be taking nifedipine and amlodipine, respectively, than patients without gingival overgrowth. On the other hand, this significant association was not observed for felodipine. Conclusion: Nifedipine and amlodipine, but not felodipine, were associated with gingival overgrowth in patients with severe refractory hypertension. [ABSTRACT FROM AUTHOR]

Abstract: Endothelium‐dependent responses were first demonstrated 40 years ago in the aorta. Since then, extensive research has been conducted in vitro using conductance vessels and materials derived from them. However, the microcirculation controls blood flow to vital organs and has been the focus of in vivo studies of endothelium‐dependent dilation beginning immediately after the first in vitro report. Initial in vivo studies employed a light/dye technique for selectively damaging the endothelium to unequivocally prove, in vivo, the existence of endothelium‐dependent dilation and in the microvasculature. Endothelium‐dependent constriction was similarly proven. Endothelium‐dependent agonists include acetylcholine (ACh), bradykinin, arachidonic acid, calcium ionophore A‐23187, calcitonin gene‐related peptide (CGRP), serotonin, histamine and endothelin‐1. Normal and disease states have been studied. Endothelial nitric oxide synthase, cyclooxygenase and cytochrome P450 have been shown to generate the mediators of the responses. Some of the key enzyme systems generate reactive oxygen species (ROS) like superoxide which may prevent EDR. However, one ROS, namely H2O2, is one of a number of hyperpolarizing factors that cause dilation initiated by endothelium. Depending upon microvascular bed, a single agonist may use different pathways to elicit an endothelium‐dependent response. Interpretation of studies using inhibitors of eNOS is complicated by the fact that these inhibitors may also inhibit ATP‐sensitive potassium channels. Other in vivo observations of brain arterioles failed to establish nitric oxide as the mediator of responses elicited by CGRP or by ACh and suggest that a nitrosothiol may be a better fit for the latter. [ABSTRACT FROM AUTHOR]

Abstract: UW and HTK solutions are the two primary organ preservation solutions most used in the United States. This study analyzes use of the two solutions in all pediatric liver transplants performed at a single center between 2001and 2017. Outcome measures included early graft function, as well as graft and patient survival. Bile duct complications were reviewed. Operative technique, immunosuppressive protocols, and donor acceptance criteria remained uniform among participating surgeons throughout the study period. There were 104 pediatric liver transplants with complete data during the study period, 75 preserved with HTK (68%) and 29 with UW (26%). Demographics were similar. Cold and warm ischemia times were similar. Peak ALT post‐transplant was higher in the UW group at both peak and post‐transplant day 3. The peak TB levels were similar. Bile duct strictures were more common in the UW group (44% vs 16%, P < .01). Early graft survival was statistically similar at 7‐, 90‐ and 365‐days post‐transplant. Cox regression graft survival was similar at 10‐years. This study suggests that use of HTK in pediatric liver transplantation is safe with outcomes similar to UW, though bile duct stricture rates may be lower with HTK. [ABSTRACT FROM AUTHOR]

Abstract: Background: Due to medical advances, growing numbers of adolescents with congenital heart disease (CHD) survive into adulthood and transferring from paediatric to adult healthcare. This transfer is significant step in a young person's life, and this study examines the views of Irish healthcare professionals' on how best to manage this transition. Methods: Purposeful sampling was used to invite participation by healthcare professionals (HCPs) from a variety of disciplines whose caseloads include adolescents and young adults with CHD. Fourteen professionals participated in semistructured interviews regarding their experiences of the transition process and their recommendations. Data were collected during Spring 2016 and analysed using thematic analysis. Results: Results indicated that the current approach to transition and transfer could be improved. Professionals identified barriers hindering the transition process such as cultural and attitudinal differences between HCPs dealing with child and adult patients, inadequate preparation and education of patients about their condition, parental reluctance to transfer, and concern about parents' role in on‐going treatment. Measures such as better support and education for both the patients and their parents were recommended, in order to facilitate a smoother transition process for all parties involved. Additionally, HCPs identified the need for better collaboration and communication, both between paediatric and adult healthcare professionals and between hospitals, to ensure greater continuity of care for patients. Conclusions: Action is required in order to improve the current transition process. Measures need to be taken to address the barriers that currently prevent a smooth transition process for young adult CHD patients. Professionals recommended the implementation of a structured transition clinic to deal with the wide variety of needs of transitioning adolescent patients and their families. Recommendations for future research are also made. [ABSTRACT FROM AUTHOR]

Summary: We report our experience with the use of (1,3)‐ß‐ d‐glucan (BDG) screening for the diagnosis of invasive aspergillosis (IA) in neutropenic patients with haematological malignancies. The performance of BDG screening was assessed retrospectively in per patient and per sample analyses. Overall, 20 among 167 patients developed IA (12%). In the per patient analysis, BDG showed 60% sensitivity and 78% specificity when the criterion for positivity was the presence of at least one BDG value ≥80 pg/mL. For 2 consecutive positive results, sensitivity decreased to 40%, while specificity increased to 93% and was similar to that of a positive galactomannan (GM; 90%). The highest specificity (97%) was observed for combined positivity of at least one BDG and at least one GM. In the per sample analysis, the specificity of BDG was 100% in the best scenario, 96% in the median scenario and 89% in the worst scenario. BDG became positive before GM in 33% of IA patients with both markers positive (n = 12). Despite good specificity for 2 consecutive positive results, the BDG test offered unsatisfactory performance for the diagnosis of IA due to low sensitivity. The combination of BDG and GM showed the potential for increasing specificity. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence, characteristics, and management of pain in older hospitalized medical patients. Design: Medical record aggregate review. Setting: Tertiary care hospital. Participants: Individuals aged 65 and older admitted to the medicine service between November 28, 2014, and May 28, 2015. Measurements: Demographic characteristics, comorbidity burden, pain characteristics, and analgesics during index hospitalization were assessed in individuals with moderate to severe pain (≥4 on 0–10 Numeric Pain Rating Scale). Results: Of 1,267 patients admitted to the medicine service, 248 (20%) had moderate to severe pain on admission (mean age 75 ± 8, 57% female, 50% white). During hospitalization, most participants received opioids (80%) and acetaminophen (74%), and few received nonsteroidal antiinflammatory drugs (9%). Participants with chronic pain had less reduction in pain intensity score from admission to discharge than those without a history of chronic pain (mean change score 3.7 vs 4.9, p=.002) and were more likely to receive opioids, adjuvant analgesics, and other analgesics (all p<.05). Conclusion: Twenty percent of older adults admitted to a general medicine service had moderate to severe pain. Further research about optimal pain management in hospitalized older adults, particularly those with chronic pain, is necessary to improve care in this population. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementia Design: Systematic review and meta‐analysis. Setting: Two authors independently searched major electronic databases from inception until June 17, 2017, for longitudinal (without a control group) and cohort (with a control group) studies reporting CV outcomes in relation to AChEIs. Randomized controlled trials were excluded because they included relatively healthy subjects. Participants: Individuals with dementia and controls. Measurements: Changes in CV parameters were summarized using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Event rates were used to assess incidence of hypertension and bradycardia. Incidence of CV events in demented patients versus in healthy controls were compared using hazard ratios (HRs). Results: Of 4,588 initial hits, 31 studies including 258,540 individuals with dementia and 2,246,592 controls were analyzed. In longitudinal and open‐label studies, AChEIs were associated with a significantly greater incidence of hypertension (n=1,573, 4%, 95% CI=2–8%, I2=47%) and bradycardia (n=13,703, 2%, 95% CI=1–6%, I2=98%). AChEIs were associated with a decrease in heart rate (SMD=–1.77, 95% CI=–3.58–0.03, I2=78%) and an increase in PR interval (SMD=0.10, 95% CI=0.008–0.19, I2=3%) from baseline. During a median follow‐up of 116 weeks, AChEIs were associated with a significantly lower risk of CV events (stroke, acute coronary syndrome, CV mortality; HR=0.63, 95% CI=0.45–0.88, I2=18%), without a significantly greater risk of bradycardic events (HR=1.40, 95% CI=0.76–2.59, I2=98%). Conclusion: AChEI therapy may be associated with negative chronotropic and hypertensive effects but also with lower risk of CV events. [ABSTRACT FROM AUTHOR]

Abstract: The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data‐driven method that is informed by clinical and patient experience and other stakeholders’ perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three‐grade‐based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice. [ABSTRACT FROM AUTHOR]

Objective: X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disorder due to mutations in the peroxisomal very long-chain fatty acyl-CoA transporter, ABCD1, with limited therapeutic options. ALD may manifest in a slowly progressive adrenomyeloneuropathy (AMN) phenotype, or switch to rapid inflammatory demyelinating cerebral disease (cALD), in which microglia have been shown to play a pathophysiological role. The aim of this study was to determine the role of patient phenotype in the immune response of ex vivo monophagocytic cells to stimulation, and to evaluate the efficacy of polyamidoamine dendrimer conjugated to the antioxidant precursor N-acetyl-cysteine (NAC) in modulating this immune response.Methods: Human monophagocytic cells were derived from fresh whole blood, from healthy (n = 4), heterozygote carrier (n = 4), AMN (n = 7), and cALD (n = 4) patients. Cells were exposed to very long-chain fatty acids (VLCFAs; C24:0 and C26:0) and treated with dendrimer-NAC (D-NAC).Results: Ex vivo exposure to VLCFAs significantly increased tumor necrosis factor α (TNFα) and glutamate secretion from cALD patient macrophages. Additionally, a significant reduction in total intracellular glutathione was observed in cALD patient cells. D-NAC treatment dose-dependently reduced TNFα and glutamate secretion and replenished total intracellular glutathione levels in cALD patient macrophages, more efficiently than NAC. Similarly, D-NAC treatment decreased glutamate secretion in AMN patient cells.Interpretation: ALD phenotypes display unique inflammatory profiles in response to VLCFA stimulation, and therefore ex vivo monophagocytic cells may provide a novel test bed for therapeutic agents. Based on our findings, D-NAC may be a viable therapeutic strategy for the treatment of cALD. Ann Neurol 2018;84:452-462. [ABSTRACT FROM AUTHOR]

Background: Self‐harm is common in youth and an important risk factor for suicide. Certain self‐harm methods might indicate a higher risk of suicide. The main aim of this study was to determine whether some methods of self‐harm in adolescents (10–17 years) and young adults (18–24 years) are associated with a particularly high risk of suicide. A secondary aim was to ascertain how different self‐harm methods might affect the probability of psychiatric follow‐up. Method: Five Swedish registers were linked in a national population‐based cohort study. All nonfatal self‐harm events recorded in specialist health care, excluding psychiatry and primary care services, among 10–24 year olds between 2000 and 2009 were included. Methods were classified as poisoning, cutting/piercing, violent method (gassing, hanging, strangulation/suffocation, drowning, jumping and firearms), other and multiple methods. Hazard Ratios (HR) for suicide were calculated in Cox regression models for each method with poisoning as the reference. Odds Ratios (OR) for psychiatric inpatient care were determined in logistic regression models. Analyses were adjusted for important covariates and stratified by age group and treatment setting (inpatient/outpatient). Results: Among adolescents with initial medical hospitalisation, use of a violent method was associated with a near eightfold increase in HR for suicide compared to self‐poisoning in the adjusted analysis [HR 7.8; 95% confidence interval (CI) 3.2–19.0]. Among hospitalised young adult women, adjusted HRs were elevated fourfold for both cutting [4.0 (1.9–8.8)] and violent methods [3.9 (1.5–10.6)]. Method of self‐harm did not affect suicide risk in young adult men. Adolescents using violent methods had an increased probability of psychiatric inpatient care following initial treatment for self‐harm. Conclusions: Violent self‐harm requiring medical hospitalisation may signal particularly high risk of future suicide in adolescents (both sexes) and in young adult women. For the latter group this is the case for cutting requiring hospitalisation as well. [ABSTRACT FROM AUTHOR]

Summary: Erythropoiesis‐stimulating agents (ESAs) were combined with ruxolitinib in 59 anaemic myelofibrosis patients (93% with Dynamic International Prognostic Scoring System [DIPSS] intermediate‐2/high risk; 52·5% transfusion‐dependent). Anaemia response (AR) rate was 54% and 76% of patients responded at 5 years. A further 15% displayed minor improvement in anaemia and 78% of patients reduced spleen size. Endogenous erythropoietin levels <125 u/l correlated with a higher AR rate (63% vs. 20%, P = 0·008). No thrombotic events or other toxicities occurred. Overall survival was 62% at 4 years, influenced by DIPSS and transfusion dependency. ESAs seem effective in improving anaemia in ruxruxolitinib‐treated myelofibrosis patients. [ABSTRACT FROM AUTHOR]

Aim: Chylothorax is a rare but life-threatening condition in newborns. Octreotide, a somatostatin analogue, is widely used as a therapeutic option in neonates with congenital and acquired chylothorax, but its therapeutic role has not been clarified yet.Methods: We performed a systematic review to assess the efficacy and safety of octreotide in the treatment of congenital and acquired chylothorax in newborns. Comprehensive research, updated till 31 October 2017, was performed by searching in PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases using the MeSH terms 'octreotide' and 'chylothorax'. Both term and preterm newborns with congenital or acquired chylothorax treated with octreotide within the 30th day of life were included. Octreotide treatment was considered effective if a progressive reduction/ceasing in drained chylous effusion occurred.Results: A total of 39 articles were included. Octreotide was effective in 47% of patients, with a slight but not significant difference between congenital (30/57; 53.3%) and acquired (9/27; 33.3%) chylothorax (P = 0.10). Marked variation in octreotide regimen was observed. The most common therapeutic scheme was intravenous infusion at a starting dose of 1 μg/kg/h, gradually increasing to 10 μg/kg/h according to the therapeutic response. Side effects were reported in 12 of 84 patients (14.3%). Only case reports were included in this review due to the lack of randomised controlled trials.Conclusion: Octreotide is a relatively effective and safe treatment option in neonates with chylothorax, especially for the congenital forms. [ABSTRACT FROM AUTHOR]

ABSTRACT: Macrophages play critical roles in wound healing process. They switch from “classically activated” (M1) phenotype in the early inflammatory phase to “alternatively activated” (M2) phenotype in the later healing phase. However, the dynamic process of macrophage phenotype switching in diabetic wounds burdened with bacteria is unclear. In this report, Pseudomonas aeruginosa, frequently detected in diabetic foot ulcers, was inoculated into cutaneous wounds of db/db diabetic mice to mimic bacterium‐infected diabetic wound healing. We observed that P. aeruginosa infection impaired diabetic wound healing and quickly promoted the expression of pro‐inflammatory genes (M1 macrophage markers) tumor necrosis factor‐α (tnf‐α), interleukin‐1β (il‐1β) and il‐6 in wounds. The expression of markers of M2 macrophages, including il‐10, arginase‐1, and ym1 were also upregulated. In addition, similar gene expression patterns were observed in macrophages isolated directly from wounds. Immunostaining showed that P. aeruginosa infection increased both the ratios of M1 and M2 macrophages in wounds compared with that in control groups, which was further confirmed by in vitro culturing macrophages with P. aeruginosa and skin fibroblast conditioned medium. However, the ratios of the expression levels of pro‐inflammatory genes to anti‐inflammatory gene il‐10 was increased markedly in P. aeruginosa infected wounds and macrophages compared with that in control groups, and P. aeruginosa prolonged the presence of M1 macrophages in the wounds. These data demonstrated that P. aeruginosa in diabetic wounds activates a mixed M1/M2 macrophage phenotype with an excessive activation of M1 phenotype or relatively inadequate activation of M2 phenotype. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? We examined whether the macrophage‐synthesized antioxidant 7,8‐dihydroneopterin was elevated in Duchenne muscular dystrophy (DMD) patients. We then examined whether 7,8‐dihydroneopterin could protect dystrophic skeletal mouse muscle from eccentric contraction‐induced force loss and improve recovery. What is the main finding and its importance? Urinary neopterin/creatinine and 7,8‐dihydroneopterin/creatinine were elevated in DMD patients. 7,8‐Dihydroneopterin attenuated eccentric contraction‐induced force loss of dystrophic skeletal mouse muscle and accelerated recovery of force. These results suggest that eccentric contraction‐induced force loss is mediated, in part, by an oxidative component and provides a potential protective role for 7,8‐dihydroneopterin in DMD. Abstract: Macrophage infiltration is a hallmark of dystrophin‐deficient muscle. We tested the hypothesis that Duchenne muscular dystrophy (DMD) patients would have elevated levels of the macrophage‐synthesized pterins, neopterin and 7,8‐dihydroneopterin, compared with unaffected age‐matched control subjects. Urinary neopterin/creatinine and 7,8‐dihydroneopterin/creatinine were elevated in DMD patients, and 7,8‐dihydroneopterin/creatinine was associated with patient age and ambulation. Urinary 7,8‐dihydroneopterin corrected for specific gravity was also elevated in DMD patients. Given that 7,8‐dihydroneopterin is an antioxidant, we then identified a potential role for 7,8‐dihydroneopterin in disease pathology. We assessed whether 7,8‐dihydroneopterin could: (i) protect against isometric force loss in wild‐type skeletal muscle exposed to various pro‐oxidants; and (ii) protect wild‐type and mdx muscle from eccentric contraction‐induced force loss, which has an oxidative component. Force loss was elicited in isolated extensor digitorum longus (EDL) muscles by 10 eccentric contractions, and recovery of force after the contractions was measured in the presence of exogenous 7,8‐dihydroneopterin. 7,8‐Dihydroneopterin attenuated isometric force loss by wild‐type EDL muscles when challenged by H2O2 and HOCl, but exacerbated force loss when challenged by SIN‐1 (NO•, O2•, ONOO−). 7,8‐Dihydroneopterin attenuated eccentric contraction‐induced force loss in mdx muscle. Isometric force production by EDL muscles of mdx mice also recovered to a greater degree after eccentric contractions in the presence of 7,8‐dihydroneopterin. The results corroborate macrophage activation in DMD patients, provide a potential protective role for 7,8‐dihydroneopterin in the susceptibility of dystrophic muscle to eccentric contractions and indicate that oxidative stress contributes to eccentric contraction‐induced force loss in mdx skeletal muscle. [ABSTRACT FROM AUTHOR]

Abstract: Background and Objectives: Despite increasing attention to the use of shared decision making (SDM) in the emergency department (ED), little is known about ED patients’ perspectives regarding this practice. We sought to explore the use of SDM from the perspectives of ED patients, focusing on what affects patients’ desired level of involvement and what barriers and facilitators patients find most relevant to their experience. Methods: We conducted semistructured interviews with a purposive sample of ED patients or their proxies at two sites. An interview guide was developed from existing literature and expert consensus and based on a framework underscoring the importance of both knowledge and power. Interviews were recorded, transcribed, and analyzed in an iterative process by a three‐person coding team. Emergent themes were identified, discussed, and organized. Results: Twenty‐nine patients and proxies participated. The mean age of participants was 56 years (range, 20 to 89 years), and 13 were female. Participants were diverse in regard to race/ethnicity, education, number of previous ED visits, and presence of chronic conditions. All participants wanted some degree of involvement in decision making. Participants who made statements suggesting high self‐efficacy and those who expressed mistrust of the health care system or previous negative experiences wanted a greater degree of involvement. Facilitators to involvement included familiarity with the decision at hand, physicians’ good communication skills, and clearly delineated options. Some participants felt that their own relative lack of knowledge, compared to that of the physicians, made their involvement inappropriate or unwanted. Many participants had no expectation for SDM and although they did want involvement when asked explicitly, they were otherwise likely to defer to physicians without discussion. Many did not recognize opportunities for SDM in their clinical care. Conclusions: This exploration of ED patients’ perceptions of SDM suggests that most patients want some degree of involvement in medical decision making but more proactive engagement of patients by clinicians is often needed. Further research should examine these issues in a larger and more representative population. [ABSTRACT FROM AUTHOR]

Aims: The aims of the present study were to characterize the pharmacokinetics of voriconazole in renal transplant recipients and to identify factors significantly affecting pharmacokinetic parameters. We also aimed to explore the optimal dosing regimens for patients who developed invasive fungal infections. Methods: A total of 105 patients (342 concentrations) were included prospectively in a population pharmacokinetic analysis. Nonlinear mixed‐effects models were developed using Phoenix NLME software. Dosing simulations were performed based on the final model. Results: A one‐compartment model with first‐order absorption and elimination was used to characterize voriconazole pharmacokinetics. Population estimates of clearance, volume of distribution and oral bioavailability were 2.88 l·h−1, 169.3 l and 58%, respectively. The allele frequencies of cytochrome P450 gene (CYP) 2C19*2, *3 and *17 variants were 29.2%, 5.2% and 0.5%, respectively. CYP2C19 genotype had a significant effect on the clearance. Voriconazole trough concentrations in poor metabolizers were significantly higher than in intermediate metabolizers and extensive metabolizers alike. The volume of distribution increased with increased body weight. The oral bioavailability was substantially lower within 1 month after transplantation but increased with postoperative time. Dosing simulations indicated that during the early postoperative period, poor metabolizers could be treated with 150 mg intravenously or 250 mg orally twice daily; intermediate metabolizers with 200 mg intravenously or 350 mg orally twice daily; and extensive metabolizers with 300 mg intravenously twice daily. Conclusions: Using a combination of CYP2C19 genotype and postoperative time to determine the initial voriconazole dosing regimens followed by therapeutic drug monitoring could help to advance individualized treatment in renal transplantation patients with invasive fungal infections. [ABSTRACT FROM AUTHOR]

In this study, different phenolic extracts were obtained from the jaboticaba skin meal (JSM), whose phenolic compounds were characterized and their antibacterial activities were assessed. Moreover, the activity of lyophilized ethanolic extract of jaboticaba skin (EEJS) on wound healing was analyzed in rats. The JSM phenolic extracts were obtained in four ways: aqueous, methanolic, ethanolic, and acetone extracts. The phenolic compounds were characterized in these extracts by high‐performance liquid chromatography, and their antibacterial activities were evaluated. The in vivo experiment was divided into four groups and received the following treatments: G1—silver sulfadiazine (positive control); G2—EEJS at 10%; G3—EEJS at 5%, and G4—EEJS at 2.5%. The aqueous extract did not inhibit the growing of any bacterium. The ethanolic, acetone, and methanolic extracts inhibited the growing of all bacteria tested at the concentrations of 1.25%, 2.50%, and 5.00%, respectively. The ethanolic extract was the one that showed the highest bacterial inhibition potential and the highest contents of phenolic compounds, especially of catechin, epicatechin gallate, and epicatechin. The G3 and G4 treatments presented faster wound healing compared to the G1 one, as it promoted a less intense inflammatory reaction and full closure of the wounds at an accelerated rate. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a chronic disease characterized by abdominal pain and changes in bowel habits. Patients with IBS comprise a significant portion of attendants at the outpatient clinics. Targeting intestinal opioid receptors was found successful in alleviating pain and diarrhea—two major symptoms of IBS. In this study, we aimed to evaluate a novel potential pharmacological option: the use of enkephalinase inhibitors in therapy of visceral pain occurring in the course of IBS. We thus assessed the antinociceptive efficacy of enkephalins: Leu‐enkephalin and Met‐enkephalin, and enkephalinase inhibitors: opiorphin and sialorphin in the mouse model of visceral pain induced by colorectal distension. Leu‐enkephalin, Met‐enkephalin, and sialorphin, but not opiorphin, at the dose of 1 mg/kg injected subcutaneously potently decreased the visceromotor response to colon distension as compared to control. To conclude, enkephalinase inhibitors are worth being considered as potential therapeutics in patients with chronic abdominal pain and/or changed bowel habits, that is, suffering from IBS. [ABSTRACT FROM AUTHOR]

Abstract: This study details a validation process for linear accelerator‐based treatment of trigeminal neuralgia using HD‐MLC field collimation. Nine trigeminal neuralgia treatment plans utilizing HD‐MLC were selected for absolute dose measurement at isocenter using a commercial scintillating detector in an anthropomorphic phantom. Four plans were chosen for film dosimetry measurements in each of the three principal planes to assess spatial dose distribution agreement with the treatment planning system. Additionally, trajectory log analysis for each treatment field in the nine cases was performed to assess mechanical positioning accuracy of the MLC system during delivery. Scintillator and film measurements both revealed mean dose agreement at isocenter of better than 3% while FWHM of the 2D dose distribution in each plane showed agreement between plan and measurement within 0.2 mm. Analysis of log files revealed a maximum MLC leaf positioning error of 0.04 mm across 178 treatment fields. In conjunction with a quality‐controlled treatment delivery methodology, an appropriately commissioned treatment planning system can be used for accurate and clinically appropriate design of trigeminal neuralgia treatment plans utilizing HD‐MLC. [ABSTRACT FROM AUTHOR]

We performed the largest randomized, placebo‐controlled clinical trial to date (N = 112, 12‐week intervention) to investigate the effects and safety of resveratrol supplementation on liver fat content and cardiometabolic risk parameters in overweight and obese and insulin‐resistant subjects. At baseline the variability in liver fat content was very large, ranging from 0.09% to 37.55% (median, 7.12%; interquartile range, 3.85%‐12.94%). Mean (SD) liver fat content was 9.22 (6.85) % in the placebo group and 9.91 (7.76) % in the resveratrol group. During the study liver fat content decreased in the placebo group (−0.7%) but not in the resveratrol group (−0.03%) (differences between groups: P = .018 for the intention‐to‐treat [ITT] population; N = 54, resveratrol, N = 54, placebo and P = .0077 for the per protocol [PP] population). No effects of resveratrol supplementation on cardiometabolic risk parameters were observed. Resveratrol supplementation was well tolerated and safe. In conclusion, these data suggest that resveratrol supplementation is safe and that it does not considerably impact liver fat content or cardiometabolic risk parameters in humans. [ABSTRACT FROM AUTHOR]

Abstract: Background: This report is intended to present a supplemental analysis of data from a prior report (Aroca et al., ) to investigate factors associated with a complete root coverage at 1 year. The purpose of the prior report was to investigate at 1 year the adjunction effect of EMD for the treatment of Miller’s class III recession defects using a coronally advanced modified tunnel/CTG technique with (test group) or without (control group). The purpose of this report was to investigate additional factors associated with root coverage in the same data set. Materials and methods: On the 138 observations collected from 20 patients, a regression model was used to highlight the relationship between the percentages of root coverage (RC) and three following covariates: the distance from the tip of the papilla and the contact point (DCP) at baseline, the group membership (control vs. test) and tooth position in the mouth (maxillary vs. mandibular). Results: The statistical analysis showed that there was a significant effect of the DCP at baseline (p = 0.01) and of the tooth type (p < .001) on the percentage of RC at 1 year, whereas no significant difference between the two techniques (group membership effect) was shown (p = 0.69). Conclusion: The probability to obtain a complete root coverage decreases when the DCP at baseline increases. Moreover, maxillary teeth are more likely to give better RC than mandibular teeth. However, in this analysis similar to the last, there was no group effect. [ABSTRACT FROM AUTHOR]

Summary: Background: Renal dysfunction remains an issue in tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients. Aim: To evaluate renal safety of TDF according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Methods: We retrospectively recruited CHB patients who received either TDF or entecavir (ETV) monotherapy from January 2008 to August 2015. After excluding confounding conditions, 253 patients who received TDF were randomly matched 1:2 with 506 patients who received ETV through the propensity scores, which consisted of age, gender, cirrhosis, chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR). Renal function deterioration was defined as a drop in GFR category accompanied with a ≥25% eGFR decline. Cumulative incidences of and hazard ratios (HRs) for renal dysfunction were analysed. Results: The mean eGFR decline was significantly greater in the TDF group over 48 months (TDF vs ETV: 15.73 mL/min/1.73 m2, 95% confidence interval [CI]: 13.76‐17.70 vs 5.96 mL/min/1.73 m2, 95% CI: 4.72‐7.19; P < 0.001). The cumulative incidence of renal function deterioration was significantly higher in the TDF group (TDF vs ETV: 11.1%, 95% CI: 7.4‐14.8 vs 1.7%, 95% CI: 1.0‐2.4; P < 0.001). After adjusting for age, pre‐existing CKD and diabetes, TDF was independently associated with an increased risk of renal function deterioration (HR 5.36, 95% CI: 2.16‐13.35; P < 0.001). Pre‐existing CKD (HR 6.71, 95% CI: 2.25‐17.65), proteinuria (HR 3.39, 95% CI: 1.23‐9.39), and haematuria (HR 4.25, 95% CI: 1.32‐13.68) were also independent factors of renal dysfunction. Conclusion: By following the KDIGO guidelines, we confirmed that TDF was associated with a higher risk of renal dysfunction as compared to ETV. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Idiopathic ventricular tachycardia arising from the LV summit epicardial area can be successfully mapped and possibly ablated from the left atrial appendage. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Osteonecrosis (ON), also known as avascular necrosis, is an important cause of physical disability in rheumatic disease. When this condition affects multiple structures, disability is increased. The purpose of this study was to describe the clinical characteristics of Korean patients with multifocal ON associated with rheumatic disease and to compare them with those of previously reported cases. Methods: We reviewed the clinical characteristics of eight Korean patients with multifocal ON, defined by the involvement of three or more anatomic sites, associated with rheumatic disease in a single referral academic hospital, and compared them with those of 19 similar cases previously reported in the literature. Results: All eight patients were female, with median age of 26 years. All had underlying systemic lupus erythematosus (SLE) and had been using corticosteroids. The most common site affected by ON was the knee joint. However, in contrast to our patients, the previous reported cases had other rheumatic diseases such as myositis, scleroderma and antiphospholipid syndrome. In comparison between Korean multifocal ON patients with SLE and those of previous reports, shoulder joint involvement was higher in previous reports. Common features in patients from both groups were knee joint involvement and prevalent use of corticosteroids. Conclusion: Our findings indicate that multifocal ON is common in young SLE patients who have been using corticosteroids and the most commonly involved site is the knee. [ABSTRACT FROM AUTHOR]

The British Association of Dermatologists (BAD) published new evidence‐based guidelines on the management of generalised pruritus (itch) in adults in 2018. This article provides an overview of the new guidance and its implications for primary care. [ABSTRACT FROM AUTHOR]

Objectives: 1) review benefits and risks of cannabis use, with emphasis on otolaryngic disease processes; 2) define and review the endocannabinoid signaling system (ESS); and 3) review state and federal regulations for the use and research of cannabis and ESS modulators. Methods: This manuscript is a review of the current literature relevant to the stated objectives. Results: Cannabis (marijuana) use is increasing. It is the most widely used illicit substance in the world. There is increasing interest in its therapeutic potential due to changing perceptions, new research, and legislation changes controlling its use. The legal classification of cannabis is complicated due to varied and conflicting state and federal laws. There are currently two synthetic cannabinoid drugs that are FDA approved. Current indications for use include chemotherapy‐related nausea and vomiting, cachexia, and appetite loss. Research has demonstrated potential benefit for use in many other pathologies including pain, inflammatory states, and malignancy. Data exists demonstrating potential antineoplastic benefit in oral, thyroid, and skin cancers. Conclusions: ESS modulators may play both a causal and therapeutic role in several disorders seen in otolaryngology patients. The use of cannabis and cannabinoids is not without risk. There is a need for further research to better understand both the adverse and therapeutic effects of cannabis use. With increasing rates of consumption, elevated public awareness, and rapidly changing legislation, it is helpful for the otolaryngologist to be aware of both the adverse manifestations of use and the potential therapeutic benefits when talking with patients. [ABSTRACT FROM AUTHOR]

Summary: Autonomic dysfunction is linked to sudden death regardless of the presence of structural heart disease. The pathway from autonomic dysfunction to sudden death is not fully understood, but myocardial sympathetic stimulation leading to arrhythmia and/or cardiac fibrosis might play a role. Our goal was to evaluate cardiac stiffness by echocardiography and its association with clinical, structural, and autonomic variables in people with epilepsy (PWE) compared to healthy controls. A 12‐lead electrocardiogram, treadmill testing, and transthoracic echocardiography from 30 patients with temporal lobe epilepsy (TLE) without any known cardiovascular disorders were compared to 30 individuals without epilepsy matched by sex, age, and body mass index. Distribution of cardiovascular risk factors was similar in both groups. PWE had a higher left ventricle stiffness, left ventricle filling pressure, and greater left atrial volume as well as markers of autonomic dysfunction such as impaired chronotropic index and percentage achieved of predicted peak heart rate at effort. In multiple regressions, autonomic dysfunction explained 52% of stiffness and carbamazepine treatment and polytherapy with antiepileptic drugs (AEDs) explained, additionally, 6% each. Stiffness is increased in young patients with TLE and is related to autonomic dysfunction and to a lesser extent, carbamazepine use and polytherapy with AEDs. [ABSTRACT FROM AUTHOR]

The article presents information about abstracts of various papers that will be discussed at the Discussion Group of the 6th European Congress on Epileptology that will be held on June 2, 2004. One of the papers that will be discussed is "Pharmacokinetic-Based Design of New Antiepileptics and CNS Drugs," by M. Bialer. Several of the new antiepileptic drugs (AEDs) are second generation or follow-up compounds of existing AEDs that their development was pharmacokinetic- (PK)-based design in order to overcome the PK drawbacks possessed by the parent compound. Other papers that will be discussed are "How to Design New CNS Drugs That Will Possess Antiepileptogenic Activity?" by A. Nehlig and "Mechanism-Based Design of New Antiepileptics and CNS Drugs," by C.E. Elger.

The article presents information about abstracts of various papers that will be discussed at the Discussion Group of the 6th European Congress on Epileptology that will be held on June 2, 2004. One of the papers that will be discussed is "Seizure Semiology and Ictal SPECT," by S. Asenbaum. One of the main purposes of nuclear medicine in neurology is the investigation of the epileptogenic zone (EZ) in the presurgical evaluation of patients with therapy refractory focal seizures. Other papers that will be discussed are "Ictal SPECT in Extratemporal Lobe Epilepsy: Contribution or Confusion?" by K. Tatsch and "Is There a Role for Benzodiazepine Receptor SPECT in Focal Epilepsy?" by J.O. Rinne.

The article presents a case study of a 58-year-old peritoneal dialysis (PD) patient who was diagnosed with acute cholecystitis. The patient underwent abdominal computed tomography (CT) and ultrasonography revealing acute cholecystitis. She was administered with ceftazidime and percutaneous transhepatic gallbladder drainage (PTGBD).

We discuss 3 alternative approaches to sample size calculation: traditional sample size calculation based on power to show a statistically significant effect, sample size calculation based on assurance, and sample size based on a decision-theoretic approach. These approaches are compared head-to-head for clinical trial situations in rare diseases. Specifically, we consider 3 case studies of rare diseases (Lyell disease, adult-onset Still disease, and cystic fibrosis) with the aim to plan the sample size for an upcoming clinical trial. We outline in detail the reasonable choice of parameters for these approaches for each of the 3 case studies and calculate sample sizes. We stress that the influence of the input parameters needs to be investigated in all approaches and recommend investigating different sample size approaches before deciding finally on the trial size. Highly influencing for the sample size are choice of treatment effect parameter in all approaches and the parameter for the additional cost of the new treatment in the decision-theoretic approach. These should therefore be discussed extensively. [ABSTRACT FROM AUTHOR]

Abstract: Background: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS‐C) was needed. Methods: This was a randomized, double‐blind, placebo‐controlled, dose‐finding trial. Japanese patients with IBS‐C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12‐week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others. Key Results: The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea. Conclusions & Inferences: This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS‐C. [ABSTRACT FROM AUTHOR]

Objectives: To provide real‐world data on Japanese patients with overactive bladder (OAB) initiating treatment with the β3‐adrenoceptor agonist, mirabegron. This study examined prescribing patterns, adverse drug reaction (ADR) incidence, and treatment effectiveness. Methods: Full medical histories, including prior/concomitant drug use, were collected before initiating mirabegron treatment. After 12 weeks mirabegron, physicians assessed ADR incidence and treatment effectiveness. Residual urine volume was assessed and patients completed the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score‐Quality of Life (I‐PSS QoL) surveys at Baseline and 12 weeks. Data were collected between April 2012 and July 2014. Results: Of 9795 OAB patients (46.8% male; 80.8% ≥65 years), 71.7% had coexisting disease [notably benign prostatic hyperplasia (BPH, 32.4%), hypertension (31.9%), and diabetes mellitus (9.4%)] and 53.4% reported concomitant drug use (27.8% α1‐antagonists, 6.3% anticholinergics). The incidence of total ADRs was 6.07% [including constipation (0.97%), thirst (0.47%), and dysuria (0.44%)], of serious ADRs, 0.21%, of cardiovascular ADRs, 0.48% and of urinary retention, 0.31%. Incidence of total ADRs in patients with concomitant cardiovascular disease was 10.09% and of those related to urinary retention in men with untreated BPH, 0.88%. After 12 weeks treatment, physicians judged mirabegron as “effective” in 80.7% of patients, 63.6% of patients achieved the three‐point minimal clinically important change from Baseline in the mean OABSS, and the I‐PSS QoL decreased significantly from Baseline (−2.1 ± 1.77; P < 0.001). Conclusions: In the clinical setting, mirabegron is well tolerated, with no unanticipated ADRs, and is an effective treatment for Japanese patients with OAB. [ABSTRACT FROM AUTHOR]

ABSTRACT: Polytraumatised patients with haemorrhagic shock are prone to develop systemic complications, such as SIRS (systemic inflammatory response syndrome), ARDS (acute respiratory distress syndrome) and MOF (multiple organ failure). The pathomechanism of severe complications following trauma is multifactorial, and it is believed that microcirculatory dysfunction plays an important role. The aim of this study was to determine the changes in the microcirculation in musculature over time during shock and subsequent resuscitation in a porcine model of haemorrhagic shock and polytrauma. Twelve pigs (German Landrace) underwent femur fracture, liver laceration, blunt chest trauma, and haemorrhagic shock under standard anaesthesia and intensive care monitoring. Microcirculation data were measured from the vastus lateralis muscle using a combined white light spectrometry and laser spectroscopy system every 15 min during the shock and resuscitation period, and at 24, 48, and 72 h. Oxygen delivery and oxygen consumption were calculated and compared to baseline. The relative haemoglobin, local oxygen consumption, and saturation values in the microcirculation were observed significantly lower during shock, however, no changes in the microcirculatory blood flow and microcirculatory oxygen delivery were observed. After resuscitation, the microcirculatory blood flow and relative haemoglobin increased and remained elevated during the whole observation period (72 h). In this study, we observed changes in microcirculation during the trauma and shock phases. Furthermore, we also measured persistent dysfunction of the microcirculation over the observation period of 3 days after resuscitation and haemorrhagic shock. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1377–1382, 2018. [ABSTRACT FROM AUTHOR]

Aim: To review indications and use of angiotensin-converting enzyme-inhibitor (ACEI) therapy for the treatment of persistent microalbuminuria (MA) and/or hypertension (HTN) in adolescents with type 1 diabetes mellitus (T1DM).Methods: Retrospective chart review of adolescent patients with T1DM seen within the paediatric diabetes service in Auckland, New Zealand, from 2006 to 2016. MA, HTN, patient demographic characteristics and ACEI prescribing and monitoring indices were examined.Results: Five hundred adolescents with T1DM were included. There were 26 patients (5%) with MA and/or HTN. MA alone was present in 16, HTN alone in 3 and both HTN and MA in 7. The 5-year MA/HTN-free rate was 98%, and the 10-year MA/HTN-free rate was 93%. Longer disease duration and earlier diagnosis were predictors of MA/HTN. There was no significant difference in standard clinical indices between study patients and others. ACEI was prescribed for 17 of 26 patients for either HTN or MA. Within 6 weeks of ACEI commencement, less than half of the subjects had repeat serum creatinine and MA screens and no record of repeat blood pressure measurement. Despite this, all patients had 3-monthly reviews within outpatient clinics where adjustments of ACEI doses were made.Conclusion: In our regional adolescent population with T1DM, there were low rates of both MA and/or HTN. In those who required treatment with ACEI, clinical monitoring post-commencement of therapy was inconsistent. Local consensus guidelines for the management of persistent MA in children and adolescents with diabetes mellitus were developed in response to this study. [ABSTRACT FROM AUTHOR]

Aim: Adenotonsillectomy is performed in children with recurrent tonsillitis or obstructive sleep apnoea. Children at risk of post-operative respiratory complications are recommended to be monitored in paediatric intensive care unit (PICU). The aim of the study is to review the risk factors for post-operative complications and admissions to PICU.Methods: A review of medical records of children who underwent adenotonsillectomy between January 2011 and December 2014 was performed. Association between demographic variables and post-operative complications were examined using chi-square and Mann-Whitney tests.Results: A total of 214 children were identified, and of these, 19 (8.8%) experienced post-operative complications. Six children (2.8%) had respiratory complications: hypoxaemia in four and laryngospasm requiring reintubation in a further two. Both of the latter patients were extubated upon arrival to PICU and required no escalation of therapy. A total of 13 (6.1%) children had non-respiratory complications: 8 (3.7%) had infection and 5 (2.3%) had haemorrhage. A total of 26 (12.1%) children were electively admitted to PICU and mean stay was 19.5 (SD ± 13) h. No association between demographic characteristics, comorbid conditions or polysomnographic parameters and post-operative complications were noted. A total of 194 (90.7%) children stayed only one night in hospital (median 1 day, range 1-5 days).Conclusion: The previously identified risk factors and criteria for PICU admission need revision, and new recommendations are necessary. [ABSTRACT FROM AUTHOR]

Summary: Objective: This study intends to study the association between serum retinol binding protein 4 (RBP4), bone mineral density (BMD) and other bone metabolic‐related parameters in type 2 diabetic patients older than 50 years, with or without osteopenia or osteoporosis. Methods: Patients (n = 274 cases) with type 2 diabetes, hospitalized in the Endocrinology Department of Yantai Yuhuangding Hospital from December 2015 to March 2017, were enrolled in the study. The bone mineral density (BMD) was recorded by the dual‐energy X‐ray absorptiometer, and patients were divided into normal bone mineral density (148 cases), osteopenia (93 cases) and osteoporosis (33 cases) groups. The serum adipokine RBP4 and other biomarkers were determined accordingly. Results: Serum RBP4, body weight, calcium and body mass index (BMI) demonstrated a positive correlation with BMD at all tested body sites in osteopenia and osteoporosis groups compared with normal bone mineral density group. In contrast, age, duration of diabetes and alkaline phosphatase (ALP) were inversely correlated with BMD at all tested body sites. In nonadjusted analyses, age, gender, duration of diabetes and ALP were inversely associated with BMD at the femoral neck, total hip and lumbar spine, while body weight, BMI and RBP4 were positively associated with BMD at all sites. In multiple regression analyses, adjusted for age, weight, BMI and other bone‐related factors, a graded stepwise positive association between serum RBP4 and BMD was shown, at all sites. Conclusion: Serum RBP4 was positively associated with BMD at all sites after adjustments for other factors in osteopenia and osteoporosis groups compared with normal bone mineral density group of type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

The article offers information on topics related to bipolar disorder (BP). Topics mentioned include the several factors needed in diagnosis of BD including mental state examination, physical examination, and medical history, the need to assess the risk of suicidal and aggressive behavior of patients with BD, and the treatment for BD.

Objectives: Due to limited research on the association between recurrence of mood episodes and the longitudinal course of neurocognitive functioning in early phase bipolar I disorder (BD I), the impact of recurrence on neurocognition remains unclear. Further, a strong correlation between neurocognitive impairment and functional impairment has been demonstrated. The longitudinal relationship between neurocognitive impairment and functional outcome in relation to recurrence is, however, not established. Methods: The current study investigated the longitudinal relationship between neurocognition, recurrence of mood episodes and functional outcome in a sample of first‐treatment (FT) BD I patients (N = 42), with and without relapse, during a 1‐year follow‐up period. The longitudinal course of neurocognitive functioning in the patients was also compared to that of a group of healthy controls (N = 143). Results: Compared to both patients with relapse and healthy controls, no‐relapse patients showed neurocognitive improvements. The polarity of the relapse episodes was mostly depressive, and for the no‐relapse patients, reduction of symptoms was associated with neurocognitive improvement. No‐relapse patients showed better global and occupational functioning. Conclusions: The current study found different neurocognitive and functional trajectories in FT BD I patients with and without relapse, with differences at follow‐up to some degree being mediated by current symptoms. The current findings highlight the importance of treatment focusing on neurocognition and symptom states with the aim of improving functional recovery. [ABSTRACT FROM AUTHOR]

Background: While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and white-matter microstructure remains limited.Objectives: This study examined whether substance-use initiation moderated the effect of perceived stress on white-matter differences using measures of primary white-matter fiber anisotropy.Methods: Forty adolescents (age 14.75 ± .87 years) were assessed on the Perceived Stress Scale, and 50% were determined to have presence of substance-use initiation. White-matter microstructure was examined using primary-fiber orientations anisotropy, which may reflect white-matter integrity, modeled separately from other fiber orientations in the same voxels. Analyses were conducted on regions of interest previously associated with childhood stress and substance use.Results: Lower perceived stress and presence of substance-use initiation were related to greater right cingulum primary-fiber measures. Substance-use-initiation status moderated the association between perceived stress and right cingulum primary-fiber measures, such that higher perceived stress was associated with lower right cingulum primary-fiber anisotropy in adolescents without substance-use initiation, but not in those with substance-use initiation.Conclusions and Scientific Significance: Findings in primary-fiber anisotropy suggest differences in right cingulum white-matter integrity is associated with substance-use initiation in higher-stress adolescents. This reflects a possible pre-existing risk factor, an impact of early substance use, or a combination thereof. Examination of potential markers associated with substance-use initiation in white-matter microstructure among stress-exposed youth warrant additional investigation as such biomarkers may inform efforts relating to tailored interventions. (Am J Addict 2018;27:217-224). [ABSTRACT FROM AUTHOR]

Aim: To evaluate whether the administration of desmopressin alters the risk for renal biopsy complications. Methods: A multicenter registry containing 576 native kidney biopsies (NKb) with a serum creatinine above 150 µmol/L in 527 patients (372 men and 155 women, median age 61 years) was used. Most of the data were prospective. At one of the hospitals all biopsies with creatinine above 150 µmol/L received desmopressin before biopsies (NKb 204). These were compared to outcome of biopsy complications against other centres where desmopressin was not given (NKb 372). Fisher's exact test, x² analyses, univariate and multiple binary logistic regression were used. Data were given as odds ratio (OR) and confidence interval (CI). A two sided P-value of <0.05 was considered significant. Results: In NKb with creatinine >150 µmol/L, those with desmopressin had less overall (3.4% vs 8.4%, OR 0.39, CI 0.17-0.90) whereas major or minor complications were not different. While desmopressin did not exhibit difference in complications in men, women received less major (0% vs 8.6%, P = 0.03) and overall complications (0% vs 12.1%, P = 0.006). A multiple logistic regression revealed that, after adjusting for BMI, age and sex, prophylaxis with desmopressin showed less major (OR 0.38, CI 0.15-0.96) and overall complications (OR 0.36, CI 0.15-0.85). Conclusion: Desmopressin given before a native kidney biopsy in patientswith impaired renal function can reduce the risk for complications. [ABSTRACT FROM AUTHOR]