Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic ...dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.
Summary Background The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and ...efficacy of bilateral constant-current DBS of the subthalamic nucleus. Methods This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18–80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov , number NCT00552474. Findings Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 95% CI 0·87–4·16; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. Interpretation Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. Funding St Jude Medical Neuromodulation Division.
Table of Contents Preamble2647 Introduction2649 Methodology and Evidence Review2649 Organization of the GWC2649 Document Review and Approval2649 Scope of the CPG2650 Overview of ACS2650 Initial ...Evaluation and Management: Recommendations2650 Clinical Assessment and Initial Evaluation2650 Emergency Department or Outpatient Facility Presentation2650 Prognosis--Early Risk Stratification2650 Cardiac Biomarkers and the Universal Definition of Myocardial Infarction2654 Biomarkers: Diagnosis2654 Biomarkers: Prognosis2654 Discharge From the ED or Chest Pain Unit2655 Early Hospital Care: Recommendations2655 Standard Medical Therapies2655 Oxygen2655 Nitrates2655 Analgesic Therapy2655 Beta-Adrenergic Blockers2656 Calcium Channel Blockers2657 Cholesterol Management2657 Inhibitors of the Renin-Angiotensin-Aldosterone System2657 Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS2657 Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTE-ACS Treated With an Initial Invasive or Ischemia-Guided Strategy2657 Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS2659 Ischemia-Guided Strategy Versus Early Invasive Strategies2659 Early Invasive and Ischemia-Guided Strategies2659 Risk Stratification Before Discharge for Patients With an Ischemia-Guided Strategy of NSTE-ACS2661 Myocardial Revascularization: Recommendations2661 PCI--General Considerations2661 PCI--Oral and Intravenous Antiplatelet Agents2661 PCI--GP IIb/IIIa Inhibitors2662 Anticoagulant Therapy in Patients Undergoing PCI2663 Timing of Urgent Coronary Artery Bypass Graft in Patients With NSTE-ACS in Relation to Use of Antiplatelet Agents2663 Late Hospital Care, Hospital Discharge, and Posthospital Discharge Care: Recommendations2663 Medical Regimen and Use of Medications at Discharge2663 Late Hospital and Posthospital Oral Antiplatelet Therapy2664 Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTE-ACS2664 Risk Reduction Strategies for Secondary Prevention2664 Plan of Care for Patients With NSTE-ACS2665 Special Patient Groups: Recommendations2665 NSTE-ACS in Older Patients2665 Heart Failure and Cardiogenic Shock2665 Diabetes Mellitus2667 Post-CABG2668 Perioperative NSTE-ACS Related to Noncardiac Surgery2668 Chronic Kidney Disease2668 Women2668 Anemia, Bleeding, and Transfusion2668 Cocaine and Methamphetamine Users2668 Vasospastic (Prinzmetal) Angina2668 ACS With Angiographically Normal Coronary Arteries2669 Stress (Takotsubo) Cardiomyopathy2669 Quality of Care and Outcomes for ACS--Use of Performance Measures and Registries: Recommendation2669 Summary and Evidence Gaps2669 References2670 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)2680 Appendix 2 Reviewer Relationships With Industry and Other Entities (Relevant)2683 Preamble The American College of Cardiology (ACC) and the American Heart Association (AHA) are committed to the prevention and management of cardiovascular diseases through professional education and research for clinicians, providers, and patients. Since 1980, the ACC and AHA have shared a responsibility to translate scientific evidence into clinical practice guidelines (CPGs) with recommendations to standardize and improve cardiovascular health.
Abstract Background Heart failure (HF) is characterized by perturbations in energy homeostasis and metabolism. The reversibility and prognostic value of circulating markers associated with these ...changes remain unclear. Objectives This study sought to describe the metabolomic profiles of patients along the spectrum of systolic HF, determine their association with adverse outcomes in a clinical trial of HF, and evaluate whether identified metabolites change with treatment for end-stage systolic HF. Methods To assess association of metabolites with clinical outcomes, we evaluated a population of 453 chronic systolic HF patients who had been randomized to exercise training versus usual care. To assess change in metabolites with mechanical circulatory support, 41 patients with end-stage HF who underwent left ventricular assist device (LVAD) placement were studied. Targeted, quantitative profiling of 60 metabolites using tandem flow injection mass spectrometry was performed on frozen plasma samples obtained prior to randomization, as well as prior to and ≥90 days post-placement in the LVAD group. Principal components analysis was used for data reduction. Results Five principal components analysis–derived factors were significantly associated with peak V o2 levels at baseline in fully adjusted models. Of these, factor 5 (composed of long-chain acylcarnitines) was associated with increased risk of all 3 pre-specified clinical trial outcomes: all-cause mortality/all-cause hospitalization, all cause-hospitalization, and cardiovascular death or cardiovascular hospitalization. Individual components of factor 5 were significantly higher in patients with end-stage HF prior to LVAD placement and decreased significantly post-implantation. Conclusions In chronic HF patients, circulating long-chain acylcarnitine metabolite levels were independently associated with adverse clinical outcomes and decreased after long-term mechanical circulatory support. These metabolites may serve as potential targets for new diagnostics or therapeutic interventions. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437 )
Abstract Heart failure patients are classified by ejection fraction (EF) into distinct groups: heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction ...(HFrEF). Although patients with heart failure commonly have multiple comorbidities that complicate management and may adversely affect outcomes, their role in the HFpEF and HFrEF groups is not well-characterized. This review summarizes the role of noncardiac comorbidities in patients with HFpEF versus HFrEF, emphasizing prevalence, underlying pathophysiologic mechanisms, and outcomes. Pulmonary disease, diabetes mellitus, anemia, and obesity tend to be more prevalent in HFpEF patients, but renal disease and sleep-disordered breathing burdens are similar. These comorbidities similarly increase morbidity and mortality risk in HFpEF and HFrEF patients. Common pathophysiologic mechanisms include systemic and endomyocardial inflammation with fibrosis. We also discuss implications for clinical care and future HF clinical trial design. The basis for this review was discussions between scientists, clinical trialists, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum.
Summary Background Previous trials have shown that anti-EGFR monoclonal antibodies can improve clinical outcomes of patients with recurrent or metastatic squamous-cell carcinoma of the head and neck ...(SCCHN). We assessed the efficacy and safety of panitumumab combined with cisplatin and fluorouracil as first-line treatment for these patients. Methods This open-label phase 3 randomised trial was done at 126 sites in 26 countries. Eligible patients were aged at least 18 years; had histologically or cytologically confirmed SCCHN; had distant metastatic or locoregionally recurrent disease, or both, that was deemed to be incurable by surgery or radiotherapy; had an Eastern Cooperative Oncology Group performance status of 1 or less; and had adequate haematological, renal, hepatic, and cardiac function. Patients were randomly assigned according to a computer-generated randomisation sequence (1:1; stratified by previous treatment, primary tumour site, and performance status) to one of two groups. Patients in both groups received up to six 3-week cycles of intravenous cisplatin (100 mg/m2 on day 1 of each cycle) and fluorouracil (1000 mg/m2 on days 1–4 of each cycle); those in the experimental group also received intravenous panitumumab (9 mg/kg on day 1 of each cycle). Patients in the experimental group could choose to continue maintenance panitumumab every 3 weeks. The primary endpoint was overall survival and was analysed by intention to treat. In a prospectively defined retrospective analysis, we assessed tumour human papillomavirus (HPV) status as a potential predictive biomarker of outcomes with a validated p16-INK4A (henceforth, p16) immunohistochemical assay. Patients and investigators were aware of group assignment; study statisticians were masked until primary analysis; and the central laboratory assessing p16 status was masked to identification of patients and treatment. This trial is registered with ClinicalTrials.gov , number NCT00460265. Findings Between May 15, 2007, and March 10, 2009, we randomly assigned 657 patients: 327 to the panitumumab group and 330 to the control group. Median overall survival was 11·1 months (95% CI 9·8–12·2) in the panitumumab group and 9·0 months (8·1–11·2) in the control group (hazard ratio HR 0·873, 95% CI 0·729–1·046; p=0·1403). Median progression-free survival was 5·8 months (95% CI 5·6–6·6) in the panitumumab group and 4·6 months (4·1–5·4) in the control group (HR 0·780, 95% CI 0·659–0·922; p=0·0036). Several grade 3 or 4 adverse events were more frequent in the panitumumab group than in the control group: skin or eye toxicity (62 19% of 325 included in safety analyses vs six 2% of 325), diarrhoea (15 5% vs four 1%), hypomagnesaemia (40 12% vs 12 4%), hypokalaemia (33 10% vs 23 7%), and dehydration (16 5% vs seven 2%). Treatment-related deaths occurred in 14 patients (4%) in the panitumumab group and eight (2%) in the control group. Five (2%) of the fatal adverse events in the panitumumab group were attributed to the experimental agent. We had appropriate samples to assess p16 status for 443 (67%) patients, of whom 99 (22%) were p16 positive. Median overall survival in patients with p16-negative tumours was longer in the panitumumab group than in the control group (11·7 months 95% CI 9·7–13·7 vs 8·6 months 6·9–11·1; HR 0·73 95% CI 0·58–0·93; p=0·0115), but this difference was not shown for p16-positive patients (11·0 months 7·3–12·9 vs 12·6 months 7·7–17·4; 1·00 0·62–1·61; p=0·998). In the control group, p16-positive patients had numerically, but not statistically, longer overall survival than did p16-negative patients (HR 0·70 95% CI 0·47–1·04). Interpretation Although the addition of panitumumab to chemotherapy did not improve overall survival in an unselected population of patients with recurrent or metastatic SCCHN, it improved progression-free survival and had an acceptable toxicity profile. p16 status could be a prognostic and predictive marker in patients treated with panitumumab and chemotherapy. Prospective assessment will be necessary to validate our biomarker findings. Funding Amgen Inc.
The General Surgery Residency Experience Anya L. Greenberg, MBA; Jenny R. Cevallos, BS; Feyisayo M. Ojute, BS ...
Annals of surgery open,
09/2022, Volume:
3, Issue:
3
Journal Article
Peer reviewed
Open access
Objectives:. We explored differences by race/ethnicity in regard to several factors that reflect or impact wellbeing. Background:. Physician wellbeing has critical ramifications for the US healthcare ...system, affecting clinical outcomes, patient experience, and healthcare economics. Within surgery, literature examining the association between race/ethnicity and wellbeing has been limited and inconclusive. Methods:. Residents at 16 academic General Surgery training programs completed an online questionnaire. Racial/ethnic identity, gender identity, post-graduate year (PGY) level, and gap years were self-reported. Differences by race/ethnicity in flourishing (global wellbeing) as well as factors reflecting resilience (mindfulness, personal accomplishment, workplace support, workplace control) and risk (depression, emotional exhaustion, depersonalization, stress, anxiety, workplace demand) were assessed. Results:. Of 300 respondents (response rate 34%), 179 (60%) were non-male, 123 (41%) were residents of color (ROC), and 53 (18%) were from racial/ethnic groups that are underrepresented in medicine (UIM). Relative to White residents, ROC have significantly lower flourishing and higher anxiety, and these remain significant when adjusting for gender, PGY level, and gap years. Relative to residents overrepresented in medicine (OIM), UIM residents have significantly lower emotional exhaustion and depersonalization after adjusting for gender, PGY level and gap years. Conclusions:. Disparities in resident wellbeing based on race/ethnicity and UIM/OIM status exist. However, the experience of ROC is not homogeneous. As part of the transformative process to address systemic racism, eliminate disparities in surgical training, and reconceptualize wellbeing as a fundamental asset for optimal surgeon performance, further understanding the specific contributors and detractors of wellbeing among different individuals and groups is critical.
Abstract Background We evaluated the overall and site-specific incidence of cancer in subjects with primary immunodeficiency diseases (PIDD) enrolled in the United States Immune Deficiency Network ...(USIDNET) registry compared with age-adjusted cancer incidence in the Surveillance, Epidemiology and End Results Program (SEER) database. We hypothesized that subjects with PIDD would have an increased incidence of cancer due to impaired immune function. Methods Overall and site-specific cancer incidence rates were evaluated in subjects with PIDD (n = 3,658) enrolled in the USIDNET registry from 2003-2015, and compared with age-adjusted incidence rates in the SEER database. Results We observed a 1.42-fold excess relative risk of cancer in subjects with PIDD compared to the age-adjusted SEER population (p<0.001). Men with PIDD had a 1.91-fold excess relative risk of cancer compared to the age-adjusted male population (p<0.001), while women with PIDD had similar overall cancer rates compared to the age-adjusted female population. Of the four most common malignancies in men and women in SEER (lung, colon, breast, and prostate cancers), we found no significant increase in these diagnoses in subjects with PIDD. Significant increases in lymphoma in both men (10-fold increase, p<0.001) and women (8.34-fold increase, p<0.001) with PIDD were observed. Conclusions Excess incidence of cancer occurred in subjects with PIDD. An excess of lymphoma in specific PIDD populations principally drove this increased incidence, while no increased risk of the most common solid tumor malignancies was observed. These data point to a restricted role of the immune system in protecting from specific cancers.
Summary Background Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an ...acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). Methods In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or non-squamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or expression of other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received infusional avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary objective was to assess safety and tolerability. This trial is registered with ClinicalTrials.gov , number NCT01772004 ; enrolment in this cohort is closed and the trial is ongoing. Findings Between Sept 10, 2013, and June 24, 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (IQR 7·2–11·9). The most common treatment-related adverse events of any grade were fatigue (46 25% of 184 patients), infusion-related reaction (38 21%), and nausea (23 13%). Grade 3 or worse treatment-related adverse events occurred in 23 (13%) of 184 patients; the most common (occurring in more than two patients) were infusion-related reaction (four 2% patients) and increased lipase level (three 2%). 16 (9%) of 184 patients had a serious adverse event related to treatment with avelumab, with infusion-related reaction (in four 2% patients) and dyspnoea (in two 1%) occurring in more than one patient. Serious adverse events irrespective of cause occurred in 80 (44%) of 184 patients. Those occurring in more than five patients (≥3%) were dyspnoea (ten patients 5%), pneumonia (nine 5%), and chronic obstructive pulmonary disease (six 3%). Immune-related treatment-related events occurred in 22 patients (12%). Of 184 patients, 22 (12% 95% CI 8–18) achieved a confirmed objective response, including one complete response and 21 partial responses. 70 (38%) had stable disease. Overall, 92 (50%) of 184 patients achieved disease control (they had a confirmed response or stable disease as their best overall response). One patient was initially thought to have died from grade 5 radiation pneumonitis during the study; however, this adverse event was subsequently regraded to grade 3 and the death was attributed to disease progression. Interpretation Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or treatment-resistant NSCLC, providing a rationale for further studies of avelumab in this disease setting. Funding Merck KGaA and Pfizer.
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