A Narrative Review of Intensive Group Tobacco Treatment: Clinical, Research, and US Policy Recommendations

Clinical practice guidelines recommend comprehensive treatment for tobacco dependence including pharmacotherapies and behavioral interventions. Group counseling may deliver unique treatment aspects not available with other modalities. This manuscript provides a narrative review of group treatment outcomes from real-world practice settings and complements recent meta-analyses of randomized controlled trials (RCTs). Our primary goals were to determine whether group treatments delivered in these settings have yielded similar quit rates compared to individual treatment and to provide recommendations for best practices and policy. Methods: Group treatment was defined as occurring in a clinical or workplace setting (ie, not provided as part of a research study), led by a professionally trained clinician, and offered weekly over several weeks. English language PubMed articles from January 2000 to July 2017 were searched to identify studies that included outcomes from both group and individual treatment offered in real-world settings. Additional data sources meeting our criteria were also included. Reports not using pharmacotherapy and research studies (eg, RCTs) were excluded. The primary outcome was short-term, carbon monoxide (CO)-validated point prevalence abstinence (4-week postquit date). Results: The review included data from 11 observational studies. In all cases, group treatment(s) had higher 4-week CO-validated quit rates (range: 35.5%-67.3%) than individual treatment(s) (range: 18.6%-53.3%). Conclusions: Best practice group treatments for tobacco dependence are generalizable from research to clinical settings and likely to be at least as effective as intensive individual treatment. The added advantages of efficiency and cost-effectiveness can be significant. Group treatment is feasible in various settings with good results. Implications: A major barrier to achieving high rates of tobacco abstinence is under-utilization of evidence-based treatment interventions. This review demonstrates the effectiveness and utility of group treatment for tobacco dependence. Based on the available data described in this narrative review in conjunction with existing RCT data, group treatment for tobacco dependence should be established and available in all behavioral health and medical settings. Group tobacco treatment is now one of the mandated reimbursable tobacco treatment formats within the US health care system, creating enormous opportunities for widespread clinical reach. Finally, comprehensive worksite group programs can further extend impact

Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC.

In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly (p = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of life (HRQoL) results from KEYNOTE-604. Patients with stage IV SCLC were randomized 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for 35 cycles plus four cycles of EP. Secondary end points included mean change from baseline to week 18 in the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) global health status/quality of life (GHS/QoL) scale and time to deterioration in the composite outcome of cough, chest pain, or dyspnea from QLQ-C30 and QLQ-Lung Cancer Module 13. Two-sided, nominal p values are reported. A total of 439 patients completed at least one QLQ-C30 and QLQ-Lung Cancer Module 13 assessment (pembrolizumab + EP, n = 221; placebo + EP, n = 218). GHS/QoL scores improved from baseline to week 18: least squares mean (95% confidence interval [CI]) changes were 8.7 (5.3-12.1) for pembrolizumab plus EP and 4.2 (0.9-7.5) for placebo plus EP. Between-group differences in least squares mean scores were improved for pembrolizumab plus EP (4.4 [95% CI: 0.2-8.7], p = 0.040]). Median time to deterioration for the composite end point was not reached and 8.7 (95% CI: 5.9-not reached) months, respectively (hazard ratio = 0.80 [95% CI: 0.56-1.14], p = 0.208). First-line pembrolizumab plus EP therapy maintained HRQoL in patients with ES-SCLC and may be associated with greater improvement than placebo plus EP. Together with the efficacy and safety findings in KEYNOTE-604, HRQoL data support the benefit of pembrolizumab in ES-SCLC

Revisiting mitochondrial ocular myopathies: a study from the Italian Network

Ocular myopathy, typically manifesting as progressive external ophthalmoplegia (PEO), is among the most common mitochondrial phenotypes. The purpose of this study is to better define the clinical phenotypes associated with ocular myopathy. This is a retrospective study on a large cohort from the database of the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”. We distinguished patients with ocular myopathy as part of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy), and then PEO with isolated ocular myopathy from PEO-plus when PEO was associated with additional features of multisystemic involvement. Ocular myopathy was the most common feature in our cohort of mitochondrial patients. Among the 722 patients with a definite genetic diagnosis, ocular myopathy was observed in 399 subjects (55.3%) and was positively associated with mtDNA single deletions and POLG mutations. Ocular myopathy as manifestation of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy, n = 131) was linked to the m.3243A>G mutation, whereas the other “PEO” patients (n = 268) were associated with mtDNA single deletion and Twinkle mutations. Increased lactate was associated with central neurological involvement. We then defined, among the PEO group, as “pure PEO” the patients with isolated ocular myopathy and “PEO-plus” those with ocular myopathy and other features of neuromuscular and multisystem involvement, excluding central nervous system. The male proportion was significantly lower in pure PEO than PEO-plus. This study reinforces the need for research on the role of gender in mitochondrial diseases. The phenotype definitions here revisited may contribute to a more homogeneous patient categorization, useful in future studies and clinical trials

Fatigue and exercise intolerance in mitochondrial diseases. Literature revision and experience of the Italian Network of mitochondrial diseases

Fatigue and exercise intolerance are common symptoms of mitochondrial diseases, but difficult to be clinically assessed. New methods to quantify these rather common complaints are strongly needed in the clinical practice. Coenzyme Q10 administration and aerobic exercise may improve exercise intolerance, but more definite studies are still pending. Herein, we have revised "how to measure" and "how to treat" these symptoms of mitochondrial patients. Subsequently, we reviewed the clinical data of the 1164 confirmed mitochondrial patients present in the Italian nation-wide database of mitochondrial disease, with special regard to exercise intolerance. We observed that more of 20% of mitochondrial patients complain of exercise intolerance. This symptom seems to be frequently associated with specific patient groups and/or genotypes. Ragged red fibers and COX-negative fibers are more often present in subjects with exercise intolerance, whereas lactate levels could not predict this symptom. Multicenter efforts are strongly needed for rare disorders such as mitochondrial diseases, and may represent the basis for more rigorous longitudinal studies

Separating 39Ar{^{39}\hbox {Ar}} from 40Ar{^{40}\hbox {Ar}} by cryogenic distillation with Aria for dark-matter searches

International audienceAria is a plant hosting a ${350}\,\hbox {m}$ cryogenic isotopic distillation column, the tallest ever built, which is being installed in a mine shaft at Carbosulcis S.p.A., Nuraxi-Figus (SU), Italy. Aria is one of the pillars of the argon dark-matter search experimental program, lead by the Global Argon Dark Matter Collaboration. It was designed to reduce the isotopic abundance of ${^{39}\hbox {Ar}}$ in argon extracted from underground sources, called Underground Argon (UAr), which is used for dark-matter searches. Indeed, ${^{39}\hbox {Ar}}$ is a $\beta$-emitter of cosmogenic origin, whose activity poses background and pile-up concerns in the detectors. In this paper, we discuss the requirements, design, construction, tests, and projected performance of the plant for the isotopic cryogenic distillation of argon. We also present the successful results of the isotopic cryogenic distillation of nitrogen with a prototype plant