Skin Cancer Screening: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Skin cancer is the most common cancer type and is a major cause of morbidity. Objective: To systematically review the benefits and harms of screening for skin cancer to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from June 1, 2015, through January 7, 2022; surveillance through December 16, 2022. Study Selection: English-language studies conducted in asymptomatic populations 15 years or older. Data Extraction and Synthesis: Two reviewers independently appraised the articles and extracted relevant data from fair- or good-quality studies; results were narratively summarized. Main Outcomes and Measures: Morbidity; mortality; skin cancer stage, precursor lesions, or lesion thickness at detection; harms of screening. Results: Twenty studies in 29 articles were included (N = 6 053 411). Direct evidence on screening effectiveness was from 3 nonrandomized analyses of 2 population-based skin cancer screening programs in Germany (n = 1 791 615) and suggested no melanoma mortality benefit at the population level over 4 to 10 years' follow-up. Six studies (n = 2 935 513) provided inconsistent evidence on the association between clinician skin examination and lesion thickness or stage at diagnosis. Compared with usual care, routine clinician skin examination was not associated with increased detection of skin cancer or precursor lesions (5 studies) or stage at melanoma detection (3 studies). Evidence on the association between clinician skin examination and lesion thickness at detection was inconsistent (3 studies). Nine studies (n = 1 326 051) found a consistent positive association between more advanced stage at melanoma detection and increasing risk of melanoma-associated and all-cause mortality. Two studies (n = 232) found little to no persistent cosmetic or psychosocial harms associated with screening. Conclusions and Relevance: A substantial nonrandomized evidence base suggests a clear association between earlier stage at skin cancer detection and decreased mortality risk. However, nonrandomized studies suggest little to no melanoma mortality benefit associated with skin cancer screening with visual skin examination in adolescents or adults and no association between routine clinician skin examination and earlier stage at melanoma detection. Evidence is inconsistent regarding whether clinician skin examination is associated with thinner melanoma lesions at detection.

Screening for Pancreatic Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Pancreatic adenocarcinoma is the third most common cause of cancer death among men and women in the United States. Objective: To systematically review benefits and harms of screening for pancreatic adenocarcinoma to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials, from January 2002 through April 27, 2018; surveillance through March 22, 2019. Study Selection: Studies of adults with or without risk factors for pancreatic adenocarcinoma (eg, family history of pancreatic cancer, personal history of new-onset diabetes) undergoing imaging-based screening; studies of treatment for adults with screen-detected or asymptomatic pancreatic adenocarcinoma. Included study designs were randomized clinical trials, nonrandomized controlled intervention studies, diagnostic accuracy studies with a reference standard, cohort studies, and case-control studies (for evaluation of harms only). Studies consisting entirely of populations with known genetic syndromes associated with pancreatic cancer were excluded. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and rated included studies for quality; data were quantitatively analyzed to calculate a pooled diagnostic yield and narratively synthesized. Main Outcomes and Measures: Mortality, morbidity, or quality of life; diagnostic accuracy of screening tests; any harm of screening or treatment. Results: Thirteen fair-quality prospective cohort screening studies (N = 1317) conducted predominantly in populations at high familial risk for pancreatic adenocarcinoma were included. No studies reported on the effect of screening on morbidity or mortality or on the effectiveness of treatment for screen-detected pancreatic adenocarcinoma. Although no studies evaluated the diagnostic accuracy of screening tests, all 13 studies reported the diagnostic yield. Yields ranged from 0 to 75 cases per 1000 persons in studies using endoscopic ultrasound, magnetic resonance imaging, and/or computed tomography-based screening. In total, 18 cases of pancreatic adenocarcinoma were detected in 1156 adults at increased familial risk and 0 cases were detected in 161 average-risk adults. In 8 studies (n = 675) assessing procedural harms of screening, no serious harms from initial screening were reported. Two studies (n = 271) found no evidence of psychosocial harms related to screening. Evidence of surgical harms was limited. Conclusions and Relevance: Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma with limited evidence of minimal harms. However, the effect of screening on morbidity and mortality in groups at high familial risk has not been studied, and no data are available in average-risk populations. There is limited evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma.

A Pragmatic Clinical Trial to Compare the Real-World Effectiveness of V-Go versus Standard Delivery of Insulin in Patients with Advanced Type 2 Diabetes.

BACKGROUND: Many patients with type 2 diabetes mellitus (T2DM) do not have adequate glycemic control, leading to poor patient outcomes and high healthcare costs. OBJECTIVE: This prospective pragmatic clinical trial evaluated V-Go, a wearable insulin delivery device, compared with standard treatment optimization (STO) among insulin-treated patients with T2DM in a real-world, community-based practice setting. METHODS: Study sites, rather than individual patients, were randomized to V-Go or STO via cluster randomization. Patients were treated according to routine clinical practice and followed up to 4 months. T2DM medications and supplies were purchased utilizing usual insurance and co-pay systems. The primary analysis was an unadjusted treatment group comparison of glycosylated hemoglobinA1c (HbA1c) change from baseline to end of study (EOS). A cost of therapy analysis was completed on patients who had received comparable baseline T2DM treatment with multiple daily basal-bolus insulin injections (MDI). RESULTS: Analysis included 415 patients (169 V-Go, 246 STO) enrolled from 52 US sites. Mean baseline HbA1c (9.6%) was higher in V-Go (9.9%, range 8.0% - 14.2%) than STO (9.3%, range 7.9% - 13.9%, p <.001). HbA1c decreased from baseline to EOS in both V-Go (-1.0%, p<.001) and STO (-0.5%, p<.001); V-Go had significantly larger decrease (p=.002). V-Go had a significant reduction (p<.001) in mean insulin total daily dose (TDD; 0.76 U/kg baseline, 0.57 U/kg EOS), not seen in STO (0.72 U/kg baseline and EOS). The MDI group included 95 (56.2%) V-Go and 113 STO (45.9%) patients. Mean baseline HbA1c was significantly higher in V-Go (9.9%) than STO (9.4%). V-Go also experienced larger decrease in HbA1c from baseline (-1.0%) than STO (-0.36%) (p=.006) with a decrease in TDD, while STO TDD remained unchanged. EOS mean per patient per day cost of diabetes treatment was lower for V-Go ($30.59) vs STO ($32.20) (p=.006). V-Go was more cost effective than STO ($24.02 per 1% drop in HbA1c vs $58.86, respectively). CONCLUSIONS: This pragmatic clinical trial demonstrated improved HbA1c levels, lower cost, and decreased insulin dose in patients with T2DM initiating V-Go vs STO in a real-world community-based practice setting. Observed baseline HbAlc indicated use of V-Go in more difficult to manage diabetes patients.

Behavioral Counseling for Skin Cancer Prevention: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Exposure to UV radiation, especially in childhood, increases skin cancer risk. Objective: To systematically review the evidence on the benefits and harms of behavioral counseling for skin cancer prevention to inform the US Preventive Services Task Force (USPSTF). Data Sources: Cochrane Central Register of Controlled Trials, MEDLINE, and PubMed were searched for studies published from January 2009 to March 31, 2016, for skin cancer prevention and from August 2005 to March 31, 2016, for skin self-examination. Surveillance in targeted publications was conducted through February 14, 2018. Studies included in previous USPSTF reports were reevaluated for inclusion. Study Selection: Fair- and good-quality studies of primary care-relevant behavioral interventions focused on improving skin cancer outcomes, intermediate outcomes, or skin cancer prevention and self-examination behaviors. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized but not pooled because of heterogeneity of measures. Main Outcomes and Measures: Skin cancer, sunburn, precursor skin lesions, sun protection behaviors, and any harms from interventions. Results: Twenty-one trials in 27 publications were included (N = 20 561). No studies assessed skin cancer outcomes in pediatric populations; 1 adult trial (n = 1356) promoting skin self-examination found no significant difference in participants diagnosed with melanoma in the intervention group vs the control group at 12-month follow-up (0 vs 1 diagnosis). There was no consistent improvement in prevention of sunburn for children (3 trials [n = 2508]) or adults (6 trials [n = 3959]). There were small to moderate increases in sun protection behavior in pediatric populations (6 trials [n = 4252]) and adults (12 trials [n = 13 099]) and small increases in skin self-examination in adults (11 trials [n = 7771]; odds ratios, 1.16-2.6). One of 3 trials of indoor tanning found an intervention effect; an appearance-focused intervention (n = 430) resulted in a smaller increase in mean indoor tanning sessions at 6 months in the intervention group vs the control group. Harms were rarely reported: 1 trial of skin self-examination (n = 1356) found an increase in skin procedures in the intervention group vs the control group at 6 months (8.0% vs 3.6%, P < .001) but not between 6 and 12 months (3.9% vs 3.3%, P = .50), and 1 trial (n = 217) found no between-group difference in skin cancer worry (28.9% vs 18.4%, P = .16). Conclusions and Relevance: Behavioral interventions can increase sun protection behavior, but there is no consistent evidence that interventions are associated with a reduction in the frequency of sunburn in children or adults and minimal evidence on skin cancer outcomes. Intervention can increase skin self-examination in adults but may lead to increased skin procedures without detecting additional atypical nevi or skin cancers.

Screening for Adolescent Idiopathic Scoliosis: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Adolescent idiopathic scoliosis (AIS), a spinal curvature of 10° or more, is the most common form of scoliosis, with a prevalence of 1% to 3%. Curves progress in approximately two-thirds of patients with AIS before skeletal maturity, and large curves (>50°) may be associated with adverse health outcomes. Objective: To systematically review evidence on benefits and harms of AIS screening for the US Preventive Services Task Force (USPSTF). Data Sources: Cochrane Central Register of Controlled Trials, MEDLINE, ERIC, PubMed, CINAHL, and relevant systematic reviews were searched for studies published from January 1966 to October 20, 2016; studies included in a previous USPSTF report were also reviewed. Surveillance was conducted through July 24, 2017. Study Selection: Fair- and good-quality studies that evaluated the accuracy of screening children and adolescents aged 10 to 18 years for AIS, the benefits of AIS treatment, the harms of AIS screening or treatment, or long-term health outcomes. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized. Main Outcomes and Measures: Health outcomes and spinal curvature in adolescence and adulthood, accuracy of screening for AIS, any harm of AIS screening or treatment. Results: Fourteen studies (N = 448 276) in 26 articles were included. Accuracy of AIS screening was highest (93.8% sensitivity; 99.2% specificity) in a cohort study of a clinic-based program using forward bend test, scoliometer, and Moiré topography screening (n = 306 082); accuracy was lower in cohort studies of 6 programs using fewer modalities (n = 141 161). Four controlled studies (n = 587) found evidence for benefit of bracing on curve progression compared with controls. A randomized clinical trial and a nonrandomized trial of exercise treatment (N = 184) found favorable reductions in Cobb angle of 0.67° to 4.9° in the intervention group compared with increases of 1.38° to 2.8° in the control group. Two cohort studies (n = 339) on long-term outcomes found that braced participants reported more negative treatment experience and body appearance compared with surgically treated or untreated participants. A study that combined a randomized clinical trial and cohort design (n = 242) reported harms of bracing, which included skin problems on the trunk and nonback body pains. There was no evidence on the effect of AIS screening on adult health outcomes. Conclusions and Relevance: Screening can detect AIS. Bracing and possibly exercise treatment can interrupt or slow progression of curvature in adolescence. However, there is little or no evidence on long-term outcomes for AIS treated in adolescence, the association between curvature at skeletal maturity and adult health outcomes, the harms of AIS screening or treatment, or the effect of AIS screening on adult health outcomes.

Lipid Screening in Childhood and Adolescence for Detection of Multifactorial Dyslipidemia: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Multifactorial dyslipidemia, characterized by elevated total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C), is associated with dyslipidemia and markers of atherosclerosis in young adulthood. Screening for dyslipidemia in childhood could delay or reduce cardiovascular events in adulthood. OBJECTIVE: To systematically review the evidence on benefits and harms of screening adolescents and children for multifactorial dyslipidemia for the US Preventive Services Task Force (USPSTF). DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, and PubMed were searched for studies published between January 1, 2005, and June 2, 2015; studies included in a previous USPSTF evidence report and reference lists of relevant studies and ongoing trials were also searched. Surveillance was conducted through April 9, 2016. STUDY SELECTION: Fair- and good-quality studies in English with participants 0 to 20 years of age. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized. MAIN OUTCOMES AND MEASURES: Outcomes included dyslipidemia (TC≥200 mg/dL or LDL-C≥130 mg/dL) and atherosclerosis in childhood; myocardial infarction and ischemic stroke in adulthood; diagnostic yield (number of confirmed cases per children screened); and harms of screening or treatment. Simulated diagnostic yield was calculated as initial screening yield × positive predictive value from a study with confirmatory testing. RESULTS: Screening of children for multifactorial dyslipidemia has not been evaluated in randomized clinical trials. Based on 1 observational study (n = 6500) and nationally representative prevalence estimates, the simulated diagnostic yield of screening for elevated TC varies between 4.8% and 12.3% (higher in obese children [12.3%] and at the ages when TC naturally peaks-7.2% at age 9-11 years and 7.2% at age 16-19 years). One good-quality randomized clinical trial (n = 663) found a modest effect of intensive dietary counseling for a low-fat, low-cholesterol diet on lipid levels at 1 year in children aged 8 to 10 years with mild to moderate dyslipidemia; mean between-group difference in TC change from baseline was -6.1 mg/dL (95% CI, -9.1 to -3.2 mg/dL; P < .001). Between-group differences dissipated by year 5. The intervention did not adversely affect nutritional status, growth, or development over the 18-year study period. One observational study (n = 9245) found that TC concentration at age 12 to 39 years was not associated with death before age 55 years. CONCLUSIONS AND RELEVANCE: The diagnostic yield of lipid screening varies by age and body mass index. No direct evidence was identified for benefits or harms of childhood screening or treatment on outcomes in adulthood. Intensive dietary interventions may be safe, with modest short-term benefit of uncertain clinical significance.

Lipid Screening in Childhood and Adolescence for Detection of Familial Hypercholesterolemia: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Familial hypercholesterolemia (FH) is characterized by elevated cholesterol concentrations early in life. Untreated FH is associated with premature cardiovascular disease in adulthood. OBJECTIVE: To systematically review the evidence on benefits and harms of screening adolescents and children for heterozygous FH for the US Preventive Services Task Force (USPSTF). DATA SOURCES: MEDLINE, the Cochrane Central Register of Controlled Trials, and PubMed were searched for studies published between January 1, 2005, and June 2, 2015; studies included in a previous USPSTF report were also searched. Surveillance was conducted through April 8, 2016. STUDY SELECTION: Fair- and good-quality studies in English with participants 0 to 20 years of age. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized. MAIN OUTCOMES AND MEASURES: Myocardial infarction and ischemic stroke in adulthood; lipid concentrations and atherosclerosis in childhood; diagnostic yield of screening; any harm of screening or treatment. RESULTS: Based on 2 studies (n = 83,241), the diagnostic yield of universal screening for FH in childhood is 1.3 to 4.8 cases per 1000 screened. There was no eligible evidence on the benefits or harms of FH screening in childhood. Eight placebo trials of statin drugs (n = 1071, 6-104 weeks) found low-density lipoprotein cholesterol (LDL-C) decreases of 20% to 40%; 1 trial (n = 214) showed a 2.01% decrease in carotid intima-media thickness with statins, compared with 1.02% with placebo (P = .02). Three placebo trials of bile acid-sequestering agents (n = 332, 8-52 weeks) showed LDL-C reductions of 10% to 20%. In 1 trial (n = 248), ezetimibe with simvastatin resulted in greater LDL-C reductions compared with simvastatin alone at 33 weeks (mean, -54.0% [SD, 1.4%] vs -38.1% [SD, 1.4%]). One trial of ezetimibe monotherapy (n = 138) showed mean LDL-C decreases of 28% (95% CI, -31% to -25%) from baseline and negligible change with placebo at 12 weeks. Eighteen studies found statins generally well tolerated. One observational study found lower, but still normal, dehydroepiandrosterone sulfate concentrations in statin-treated males with FH at 10-year follow-up. Bile acid-sequestering agents were commonly associated with adverse gastrointestinal symptoms and poor palatability. There was no eligible evidence on the effect of FH treatment on myocardial infarction or stroke in adulthood. CONCLUSIONS AND RELEVANCE: Screening can detect FH in children, and lipid-lowering treatment in childhood can reduce lipid concentrations in the short term, with little evidence of harm. There is no evidence for the effect of screening for FH in childhood on lipid concentrations or cardiovascular outcomes in adulthood, or on the long-term benefits or harms of beginning lipid-lowering treatment in childhood.

Mixed-phase oxide catalyst based on Mn-mullite (Sm, Gd)Mn2O5 for NO oxidation in diesel exhaust.

Oxidation of nitric oxide (NO) for subsequent efficient reduction in selective catalytic reduction or lean NO(x) trap devices continues to be a challenge in diesel engines because of the low efficiency and high cost of the currently used platinum (Pt)-based catalysts. We show that mixed-phase oxide materials based on Mn-mullite (Sm, Gd)Mn(2)O(5) are an efficient substitute for the current commercial Pt-based catalysts. Under laboratory-simulated diesel exhaust conditions, this mixed-phase oxide material was superior to Pt in terms of cost, thermal durability, and catalytic activity for NO oxidation. This oxide material is active at temperatures as low as 120°C with conversion maxima of ~45% higher than that achieved with Pt. Density functional theory and diffuse reflectance infrared Fourier transform spectroscopy provide insights into the NO-to-NO(2) reaction mechanism on catalytically active Mn-Mn sites via the intermediate nitrate species.