Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory ...diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP. Common terms and end points of BP are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. These recommendations from the International Pemphigoid Committee represent 2 years of collaborative efforts to attain mutually acceptable common definitions for BP and proposes a disease extent score, the BP Disease Area Index. These items should assist in the development of consistent reporting of outcomes in future BP reports and studies.
Eating Disorders Andersen, Arnold E; Mehler, Philip S
2022
eBook
A comprehensive guide on how to diagnose, treat, and care for those with eating disorders.Eating disorders, which include such conditions as anorexia, bulimia, binge eating, and pica, represent a ...challenge to both patients and health care providers alike. For more than 20 years, health care providers have turned to the expert advice found in Eating Disorders to keep up to date with the latest research in the field and to help them provide the best care available for their patients. In this new, thoroughly revised and expanded edition of their best-selling work, Drs. Philip S. Mehler and Arnold E. Andersen provide a user-friendly and comprehensive guide to treating and managing eating disorders for primary care physicians, mental health professionals, worried family members and friends, and nonmedical professionals (such as teachers and coaches). Mehler and Andersen • identify common medical complications faced by people who have eating disorders• answer questions about how to treat both physical and behavioral aspects of eating disorders• discuss serious complications, including cardiac arrhythmia, electrolyte abnormalities, and gastrointestinal problems• incorporate all-new information on avoidant restrictive food intake disorder (ARFID), binge eating disorder, and the role of social media in promoting disordered eating• offer targeted advice for working with specialists• include four new chapters on eating disorders in children and adolescents; atypical anorexia; eating disorders in transgender individuals; and family therapy• feature engaging clinical vignettes • answer a list of common questions practitioners may have in each chapterThe most comprehensive work on the market and the only book that covers eating disorders in transgender individuals, Eating Disorders is a compassionate, evidence-based, and essential guide.Contributors: Arnold E. Andersen, Ovidio Bermudez, Jeana Cost, Meghan Foley, Dennis Gibson, Neville Golden, Sacha Gorell, Jeffrey Hollis, Mori J. Krantz, Daniel Le Grange, Russell Marx, Jennifer McBride, Philip S. Mehler, Leah Puckett, Katherine Sachs, Michael Spaulding-Barclay, Anna Tanner, Nathalia Trees, Jessica Tse, Kenneth Weiner, Patricia Westmoreland
Right ventricular (RV) failure is a source of morbidity and mortality after left ventricular assist device (LVAD) implantation. In this study we sought to define hemodynamic changes in afterload and ...RV adaptation to afterload both early after implantation and with prolonged LVAD support.
We reviewed right heart catheterization (RHC) data from participants who underwent continuous-flow LVAD implantation at our institutions (n = 244), excluding those on inotropic or vasopressor agents, pulmonary vasodilators or additional mechanical support at any RHC assessment. Hemodynamic data were assessed at 5 time intervals: (1) pre-LVAD (within 6 months); (2) early post-LVAD (0 to 6 months); (3) 7 to 12 months; (4) 13 to 18 months; and (5) very late post-LVAD (18 to 36 months).
Sixty participants met the inclusion criteria. All measures of right ventricular load (effective arterial elastance, pulmonary vascular compliance and pulmonary vascular resistance) improved between the pre- and early post-LVAD time periods. Despite decreasing load and pulmonary artery wedge pressure (PAWP), RAP remained unchanged and the RAP:PAWP ratio worsened early post-LVAD (0.44 0.38, 0.63 vs 0.77 0.59, 1.0, p < 0.001), suggesting a worsening of RV adaptation to load. With continued LVAD support, both RV load and RAP:PAWP decreased in a steep, linear and dependent manner.
Despite reducing RV load, LVAD implantation leads to worsened RV adaptation. With continued LVAD support, both RV afterload and RV adaptation improve, and their relationship remains constant over time post-LVAD. These findings suggest the RV afterload sensitivity increases after LVAD implantation, which has major clinical implications for patients struggling with RV failure.
Abstract Background In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments. ...Objectives It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response. Methods In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate <60 ml/min/1.73 m2 ; 2) hyponatremia; or 3) diuretic resistance (urine output ≤125 ml/h following intravenous furosemide ≥40 mg). The primary endpoint was a 7-point change in self-assessed dyspnea at 8 and 16 h, using a novel standardized approach. Results We randomized 250 patients. There was no difference in the primary endpoint of day 1 dyspnea reduction, despite significantly greater weight reduction with tolvaptan (−2.4 ± 2.1 kg vs. −0.9 ± 1.8 kg; p < 0.001). At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings. Conclusions Despite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management SECRET of CHF; NCT01584557 )
To analyze the temporal trend in enrollment rates in a COVID-19 platform trial during the first three waves of the pandemic in the United States.
Secondary analysis of data from the I-SPY COVID ...randomized controlled trial (RCT).
Thirty-one hospitals throughout the United States.
Patients who were approached, either directly or via a legally authorized representative, for consent and enrollment into the I-SPY COVID RCT.
None.
Among 1,338 patients approached for the I-SPY COVID trial from July 30, 2020, to February 17, 2022, the number of patients who enrolled (
= 1,063) versus declined participation (
= 275) was used to calculate monthly enrollment rates. Overall, demographic and baseline clinical characteristics were similar between those who enrolled versus declined. Enrollment rates fluctuated over the course of the COVID-19 pandemic, but there were no significant trends over time (Mann-Kendall test,
= 0.21). Enrollment rates were also comparable between vaccinated and unvaccinated patients. In multivariable logistic regression analysis, age, sex, region of residence, COVID-19 severity of illness, and vaccination status were not significantly associated with the decision to decline consent.
In this secondary analysis of the I-SPY COVID clinical trial, there was no significant association between the enrollment rate and time period or vaccination status among all eligible patients approached for clinical trial participation. Additional studies are needed to better understand whether the COVID-19 pandemic has altered clinical trial participation and to develop strategies for encouraging participation in future COVID-19 and critical care clinical trials.
The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of ...antibody-mediated rejection (AMR) in heart transplantation.
The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus.
A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided.
The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues.
Summary Background Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol, increased plasma LDL cholesterol concentrations, and premature ...cardiovascular disease. Despite intensive statin therapy, with or without ezetimibe, many patients are unable to achieve recommended target levels of LDL cholesterol. We investigated the effect of PCSK9 inhibition with evolocumab (AMG 145) on LDL cholesterol in patients with this disorder. Methods This multicentre, randomised, double-blind, placebo-controlled trial was undertaken at 39 sites (most of which were specialised lipid clinics, mainly attached to academic institutions) in Australia, Asia, Europe, New Zealand, North America, and South Africa between Feb 7 and Dec 19, 2013. 331 eligible patients (18–80 years of age), who met clinical criteria for heterozygous familial hypercholesterolaemia and were on stable lipid-lowering therapy for at least 4 weeks, with a fasting LDL cholesterol concentration of 2·6 mmol/L or higher, were randomly allocated in a 2:2:1:1 ratio to receive subcutaneous evolocumab 140 mg every 2 weeks, evolocumab 420 mg monthly, or subcutaneous placebo every 2 weeks or monthly for 12 weeks. Randomisation was computer generated by the study sponsor, implemented by a computerised voice interactive system, and stratified by LDL cholesterol concentration at screening (higher or lower than 4·1 mmol/L) and by baseline ezetimibe use (yes/no). Patients, study personnel, investigators, and Amgen study staff were masked to treatment assignments within dosing frequency groups. The coprimary endpoints were percentage change from baseline in LDL cholesterol at week 12 and at the mean of weeks 10 and 12, analysed by intention-to-treat. This trial is registered with ClinicalTrials.gov , number NCT01763918. Findings Of 415 screened patients, 331 were eligible and were randomly assigned to the four treatment groups: evolocumab 140 mg every 2 weeks (n=111), evolocumab 420 mg monthly (n=110), placebo every 2 weeks (n=55), or placebo monthly (n=55). 329 patients received at least one dose of study drug. Compared with placebo, evolocumab at both dosing schedules led to a significant reduction in mean LDL cholesterol at week 12 (every-2-weeks dose: 59·2% reduction 95% CI 53·4–65·1, monthly dose: 61·3% reduction 53·6–69·0; both p<0·0001) and at the mean of weeks 10 and 12 (60·2% reduction 95% CI 54·5–65·8 and 65·6% reduction 59·8–71·3; both p<0·0001). Evolocumab was well tolerated, with rates of adverse events similar to placebo. The most common adverse events occurring more frequently in the evolocumab-treated patients than in the placebo groups were nasopharyngitis (in 19 patients 9% vs five 5% in the placebo group) and muscle-related adverse events (ten patients 5% vs 1 1%). Interpretation In patients with heterozygous familial hypercholesterolaemia, evolocumab administered either 140 mg every 2 weeks or 420 mg monthly was well tolerated and yielded similar and rapid 60% reductions in LDL cholesterol compared with placebo. Funding Amgen Inc.
Summary Background Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous ...non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta. Methods Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m2 cyclophosphamide and 10 μg per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation. Findings Between January, 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8–11) and patients were discharged from hospital on mean day 11 (range day 8–13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24–48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0·0001), neurological rating scale score (p=0·0001), paced auditory serial addition test (p=0·014), 25-foot walk (p<0·0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0·0001). Interpretation Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial. Funding Division of Immunotherapy, Northwestern University.
Hospital-acquired pneumonia is common after traumatic brain injury, and might be partly a result of traumatic brain injury-induced adrenal insufficiency. We tested the efficacy of low-dose ...hydrocortisone with fludrocortisone for the prevention of hospital-acquired pneumonia.
We did this double-blind, phase 3, placebo-controlled trial in 19 intensive care units in France. We enrolled patients aged 15-65 years in the first 24 h after severe traumatic brain injury (Glasgow coma scale score ≤8 and trauma-associated lesion on brain CT scan). Patients were randomly assigned (1:1; fixed blocks of 12, stratified by centre and mechanism, Glasgow coma scale, age, and arterial pressure MGAP score) to receive either hydrocortisone (200 mg per day tapered) and fludrocortisone (50 μg tablet once per day) or matching placebo for 10 days. Before receiving study drug, adrenal function was assessed with a short corticotropin test. Treatment was stopped if patients had no adrenal insufficiency. The primary outcome was the occurrence of hospital-acquired pneumonia within 28 days after randomisation. We did an intention-to-treat analysis and a modified intention-to-treat analysis including only patients with adrenal insufficiency (adjusted for etomidate use). This study is registered with ClinicalTrials.gov, number NCT01093261.
From Sept 1, 2010, to Nov 29, 2012, we enrolled 336 patients (168 assigned to each group). Eight patients withdrew consent. At day 28, 74 of 165 patients (45%) in the steroid group and 87 of 163 (53%) in the placebo group had developed one or more episodes of hospital-acquired pneumonia (hazard ratio HR 0.75; 95% CI 0.55-1.03, p=0.07). In intention-to-treat analysis, we recorded 86 episodes of hospital-acquired pneumonia in the steroid group versus 110 in the placebo group (median 0, IQR 0-1 vs median 1, IQR 0-1 cases per patient, p=0.07). In modified intention-to-treat analyses, the HR for hospital-acquired pneumonia with steroids versus placebo was 0.80 (95% CI 0.56-1.14, p=0.22) in patients with adrenal insufficiency, and, in an exploratory preplanned analysis, 0·48 (0·23-1·01; p=0·05) in patients with normal adrenal function. We recorded no adverse events related to treatment.
Low-dose hydrocortisone with fludrocortisone did not improve the outcome of patients with traumatic brain injury. However, the study was underpowered because the proportion of patients with hospital-acquired pneumonia in the placebo group was lower than expected. The results were close to statistical significance for efficacy, meaning that further studies are therefore needed.
Société Française d'Anesthésie Réanimation.
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