Exposure to solar ultraviolet (UV) radiation is a known risk factor in the development of cutaneous melanoma. While research has shown that the use of sunscreen decreases the risk of sunburn, squamous cell carcinoma, actinic keratosis and nevi in children, there is little high-quality evidence demonstrating that melanoma can be prevented through sunscreen use. In this prospective population-based cohort study, 143,844 women age 40 to 75 years were followed up to determine whether the use of high-SPF (SPF 15 or greater) sunscreen is associated with a lower risk of melanoma compared to use of no or low-SPF (SPF <15) sunscreen in the setting of intentional sunbathing. Researchers found that after a mean follow-up time of 10.7 years (range 1.0 to 15.6 years), 722 women were diagnosed with an incident melanoma. Importantly, users and non-users of sunscreen were significantly different, with sunscreen users more likely to be in the youngest age groups, live in areas with high ambient UV radiation, have higher education, lighter skin colour, blond or red hair, and freckling when sunbathing (p < 0.001 for each). Sunscreen users also reported significantly more sunburns, sunbathing vacations and use of indoor tanning facilities (p < 0.001). Researchers also found that the use of high-SPF sunscreen was associated with a significantly reduced risk of incident melanoma compared to those consistently using sunscreen with SPF <15 or no sunscreen at all (HR 0.67, 95% CI: 0.53 to 0.83). The estimated decrease in incident melanoma with general use of SPF>15 sunscreens in women age 40 to 75 years was 18% (95% CI: 4% to 30%). This study therefore shows that the use of sunscreens with SPF of 15 or greater may reduce the risk of developing incident melanoma in women age 40 to 75 years.
The widespread use of prostate-specific antigen (PSA) testing has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer. However, many men do not benefit from intervention due to the presence of either indolent or disseminated disease at the time of diagnosis. As part of the Prostate Testing for Cancer and Treatment (ProtecT) trial conducted in the United Kingdom (1999 to 2009), 2,664 men age 50 to 69 years diagnosed with localized prostate cancer were randomized to undergo active monitoring, radical prostatectomy or radiotherapy. In this follow-up report of the original ProtecT trial, the authors reported on the effectiveness of each intervention with respect to prostate-cancer-specific mortality, all-cause mortality, and the incidence of metastases and disease progression at a median of 10 years of follow-up. Researchers found that prostate-cancer-specific survival was at least 98.8% in all groups, and there was no significant difference among the three randomized groups (p = 0.48). In addition, deaths from any cause were evenly distributed across the treatment groups (p = 0.87), however, the confidence intervals for the estimated hazard ratios were wide, and therefore, did not provide strong evidence of equivalence across the groups. With respect to disease progression, the incidence was higher in the active-monitoring group than in the surgery and radiotherapy groups (p<0.001). Based on this, the authors estimated that 27 men would need to be treated with prostatectomy rather than receive active monitoring to avoid 1 patient having metastatic disease, and that 33 men would need to be treated with radiotherapy rather than receive active monitoring to avoid 1 patient having metastatic disease. A total of 9 men would need to be treated with either prostatectomy or radiotherapy to avoid 1 patient experiencing clinical progression. This study therefore shows that after a median follow-up of 10 years, prostate cancer-specific mortality was low, irrespective of the treatment assigned, with no significant difference between treatments. However, surgery and radiotherapy are associated with lower incidences of disease progression compared to active monitoring.
The onset of macrovascular and microvascular complications in patients with type 1 diabetes can be delayed through tight control of blood glucose. However, glucose levels must also be closely monitored to prevent hypoglycemia. Continuous glucose monitoring facilitates self-management and has been shown to not only improve glucose control, but also reduce exposure to hypoglycemia. Current continuous glucose monitoring devices, however, have a relatively short sensor lifetime and require self-monitoring of blood glucose for device calibration to ensure sensor accuracy. These limitations have restricted the use of continuous glucose monitoring devices. In this randomized controlled trial, 239 patients were randomized to use a novel flash sensor-based glucose monitoring or to self-monitor blood glucose (control) to determine the effect of the intervention on exposure to hypoglycemia in patients with type 1 diabetes. The primary effectiveness endpoint was time spent in hypoglycemia (>3.9 mmol/L [70 mg/dL) for the 14 days preceding the end of the 6 month study period. Researchers found that the mean time in hypoglycemia changed from 3.38 hours/day at baseline to 2.03 hours/day at 6 months in the intervention group. This corresponded to a mean change of -1.39 hours, which was significantly greater than the mean change of -0.14 hours/day seen the control group (p<0.0001). This study therefore shows that novel flash glucose testing can reduce the time patients with well-controlled type 1 diabetes spend in hypoglycemia.
Invasive coronary angiography is commonly used in early diagnostic pathways in patients with suspected coronary heart disease (CHD). However, research has shown that the majority of patients presenting with chest pain do not have significant obstructive coronary disease. Myocardial perfusion scintigraphy (MPS) by single-photon emission computer tomography is the most commonly used test for the assessment of myocardial ischemia, with robust evidence supporting its prognostic value. However, cardiovascular magnetic resonance (CMR) has been increasingly recognized as having high diagnostic accuracy and prognostic value as well. In this randomized controlled trial, 1202 patients with suspected CHD were randomized to management according to National Institute for Health and Care Excellence (NICE) guidelines-directed care, CMR-guided care or MPS-guided care to determine whether CMR-guided care is superior in reducing unnecessary angiography. Researchers found that the percentage of patients with invasive coronary angiography after 12 months in the NICE guidelines group was 42.5% (95% CI 36.2% to 49.0%), 17.7% (95% CI 14.4% to 21.4%) in the CMR group, and 16.2% (95% CI 13.0% to 19.8%) in the MPS group. This translated to an adjusted odds ratio of unnecessary angiography of 0.21 (95% CI 0.12 to 0.34, p<0.001) with CMR-guided care, where NICE-guided care was the reference. A major adverse cardiovascular event was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group. However, these findings were not statistically significant. This study therefore shows that in patients with suspected CHD, investigation using CMR may result in a lower probability of unnecessary angiography compared to NICE guideline-directed care, with no statistically significant difference between CMR and MPS.
Closed loop artificial pancreas technology uses a control algorithm to automatically adjust insulin delivery based on subcutaneous sensor data. While currently available systems stop insulin in response to low sensor glucose values, hybrid closed-loop systems combine user-delivered pre-meal boluses with automatic inter-prandial insulin delivery. In this prospective cohort study, 124 patients with type 1 diabetes were followed up for 3 months to study the safety of a hybrid closed-loop insulin delivery system. Researchers found that over the course of 12,389 patient-days, no episodes of severe hypoglycemia or ketoacidosis were observed, however, there were 28 device-related adverse events, including skin irritation, hyperglycemia and rash. An analysis of severe hyperglycemia events showed that these were often due to the infusion set, hardware issues, and on one occasion, a sensor issue. There was also 4 serious adverse events, including appendicitis, bacterial arthritis, worsening rheumatoid arthritis and Clostridium difficile diarrhea, and 117 adverse events unrelated to the system. With respect to blood glucose control, glycated hemoglobin levels changed from a mean of 7.4% (SD 0.9) at baseline to 6.9% (SD 0.6) by the end of the study. This study therefore shows that hybrid closed-loop automated insulin delivery may be associated with few serious or device-related adverse events in patients with type 1 diabetes. It should be noted, however, that this study is limited by its lack of a control group and short length of study. Randomized studies are needed in further characterizing the safety and efficacy of the hybrid closed-loop system.
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