Strategies for secondary use of real-world clinical and administrative data for outcome ascertainment in pragmatic clinical trials.

BACKGROUND: Pragmatic trials are gaining popularity as a cost-effective way to examine treatment effectiveness and generate timely comparative evidence. Incorporating supplementary real-world data is recommended for robust outcome monitoring. However, detailed operational guidelines are needed to inform effective use and integration of heterogeneous databases. OBJECTIVE: Lessons learned from the Veterans Affairs (VA) Diuretic Comparison Project (DCP) are reviewed, providing adaptable recommendations to capture clinical outcomes from real-world data. METHODS: Non-cancer deaths and major cardiovascular (CV) outcomes were determined using VA, Medicare, and National Death Index (NDI) data. Multiple ascertainment strategies were applied, including claims-based algorithms, natural language processing, and systematic chart review. RESULTS: During a mean follow-up of 2.4 (SD = 1.4) years, 907 CV events were identified within the VA healthcare system. Slight delays (∼1 year) were expected in obtaining Medicare data. An additional 298 patients were found having a CV event outside of the VA in 2016 - 2021, increasing the CV event rate from 3.5 % to 5.7 % (770 of 13,523 randomized). NDI data required âˆ¼2 years waiting period. Such inclusion did not increase the number of deaths identified (all 894 deaths were captured by VA data) but enhanced the accuracy in determining cause of death. CONCLUSION: Our experience supports the recommendation of integrating multiple data sources to improve clinical outcome ascertainment. While this approach is promising, hierarchical data aggregation is required when facing different acquisition timelines, information availability/completeness, coding practice, and system configurations. It may not be feasible to implement comparable applications and solutions to studies conducted under different constraints and practice. The recommendations provide guidance and possible action plans for researchers who are interested in applying cross-source data to ascertain all study outcomes.

Incidental melanomas detected in veterans referred to dermatology.

BACKGROUND: Early detection of melanoma is integral to preventing morbidity and mortality. OBJECTIVE: We sought to characterize and compare incidental versus consult melanomas detected in veterans referred to the Minneapolis, MN, Department of Veterans Affairs Medical Center dermatology clinic. METHODS: We retrospectively reviewed charts of all dermatology consults between January 2004 and March 2012. RESULTS: Of the 28,405 consults sent during the study period, 17,174 met inclusion criteria. There were 231 melanomas identified in 221 patients. In all, 144 melanomas were identified on the consult and 87 melanomas were discovered incidentally. The incidental melanoma detection rate was 0.5% (84/17,174). Consult melanomas were more likely to be invasive than incidental melanomas (relative risk 1.51, 95% confidence interval 1.23-1.86, P < .0001) and less likely to have a Breslow depth of less than 1.00 mm (relative risk 0.73, 95% confidence interval 0.61-0.88, P = .0036). Incidental melanomas were smaller than consult melanomas (mean diameter 0.98 vs 1.3 cm, respectively) and thinner (mean Breslow depth 0.64 vs 1.74 mm). Consult melanomas were more likely to be detected on the head/neck (relative risk 1.25, 95% confidence interval 1.03-1.52, P = .0295). LIMITATIONS: Nondiverse patient population is a limitation. CONCLUSION: Melanomas detected during an in-person skin examination by a dermatologist were more likely to be detected at an earlier stage of disease.

Incidental lesions found in veterans referred to dermatology: the value of a dermatologic examination.

BACKGROUND: Few studies have evaluated the detection of incidental skin cancers. OBJECTIVE: We sought to evaluate the rate of incidental cutaneous malignancies in routine dermatology consults. METHODS: This was a retrospective chart review of all dermatology consults at the Minneapolis Department of Veterans Affairs Medical Center over 8.25 years. Inclusion criteria included an in-person clinic visit within 18 months of the initial consult date. Patients with an in-person skin examination by a dermatologist in the 18 months before consult date were excluded. RESULTS: Of 28,405 consults sent during the study period, 17,174 met inclusion criteria. In all, 2257 (13.1%) patients had 1 or more biopsied incidental lesions. Half (50.3%; n = 1674) of the 3328 biopsied incidental lesions were malignant, which included 1187 patients. The per-person detection rate for an incidental malignant lesion was 6.9% (1187/17,174). There were 87 incidental melanomas identified in 84 patients. The per-person detection rate for an incidental melanoma was 0.5% (84/17,174). The most frequent anatomical location for biopsied incidental malignancies was the head and neck (53.9%). Incidental melanomas were most frequently located on the back (33.3%). LIMITATIONS: Nondiverse patient population and conservative detection rate estimates are limitations. CONCLUSION: An in-person skin examination by a trained dermatologist is important for detection of skin malignancies. This may have implications for teledermatology.

Positive patch test reactions in older individuals: retrospective analysis from the North American Contact Dermatitis Group, 1994-2008.

BACKGROUND: Relatively little is known about the epidemiology of allergic contact dermatitis in older individuals. OBJECTIVES: We sought to determine the frequency of positive and clinically relevant patch test reactions in older individuals (≥ 65 years old) referred for patch testing, and to compare these results with those of adults (≤ 64-19 years) and children (<18 years). DESIGN: This was a retrospective cross-sectional analysis of North American Contact Dermatitis Group data from 1994 to 2008. RESULTS: A total of 31,942 patients (older n = 5306; adults n = 25,028; children n = 1608) were patch tested. The overall frequency of at least one allergic reaction in older individuals was 67.3% as compared with 66.9% for adults (P = .5938) and 47% for children (P = .0011). Reaction rates that were statistically higher in older individuals as compared with both adults and children included: Myroxylon pereirae, fragrance mix I, quaternium-15, formaldehyde, imidazolidinyl urea, diazolidinyl urea, neomycin, bacitracin, methyldibromo glutaronitrile, methyldibromo glutaronitrile/phenoxyethanol, ethyleneurea melamine formaldehyde mix, and carba mix (P values < .0004). Patch test reaction rates that were significantly lower in older individuals than both comparison groups included: nickel, thimerosal, and cobalt (P values < .0001). LIMITATIONS: Referral population was a limitation. CONCLUSIONS: Older individuals were more likely to have at least one positive patch test reaction as compared with children, but had similar rates to adults. The frequency of positive reactions to specific allergens differed by age group, most likely as a result of exposures.

Adverse reactions to sunscreen agents: epidemiology, responsible irritants and allergens, clinical characteristics, and management.

Sunscreen is a key component in the preventive measures recommended by dermatologists and public health campaigns aimed at reducing sunburn, early skin aging, and skin cancer. To maximize compliance, adverse reactions to sunscreens should be minimized. Although inactive ingredients cause many of these reactions, it is important for dermatologists to be aware of reactions to active ultraviolet filters. There are approximately 120 chemicals that can function as ultraviolet (UV) filters. This review focuses on the 36 most common filters in commercial and historical use. Of these, 16 are approved for use by the US Food and Drug Administration. The benzophenones and dibenzoylmethanes are the most commonly implicated UV filters causing allergic and photoallergic contact dermatitis (PACD) reactions; benzophenone-3 is the leading allergen and photoallergen within this class. When clinically indicated, patch and photopatch testing should be performed to common UV filters.

Benzophenones.

Benzophenones are ultraviolet light filters that have been documented to cause a myriad of adverse cutaneous reactions, including contact and photocontact dermatitis, contact and photocontact urticaria, and anaphylaxis. In recent years, they have become particularly well known for their ability to induce allergy and photoallergy. Topical sunscreens and other cosmetics are the sources of these allergens in most patients, but reports of reactions secondary to use of industrial products also exist. Benzophenones as a group have been named the American Contact Dermatitis Society's Allergen of the Year for 2014 to raise awareness of both allergy and photoallergy to these ubiquitous agents.

Concomitant patch test reactions to mercapto mix and mercaptobenzothiazole: retrospective analysis from the North American Contact Dermatitis Group, 1994-2008.

BACKGROUND: Mercaptobenzothiazole (MBT) and mercapto compounds are primarily used in rubber products. OBJECTIVE: This study aimed to examine concomitant-positive rates of MBT (1% pet) and the 4-part mercapto mix (MM) (1% pet). DESIGN: This is a retrospective cross-sectional data from the North American Contact Dermatitis Group. RESULTS: A total of 30,880 patients were patch tested to MM and MBT. There were 333 positive reactions to MM and 427 positive reactions to MBT. Ninety-eight patients were positive to MM alone, 192 to MBT alone, and 235 reacted to both. Forty-five percent (192/427) of MBT reactions would have been missed by only testing to MM, and 29% (98/333) of MM reactions would have been missed by testing to MBT alone. Most of these "missed" reactions, however, were doubtful (+/-) or mild (+) (MBT, 65%; MM, 78%), whereas most reactions in patients who reacted to both were moderate (++) and/or strong (+++) (52.3%). Gloves were the most common source. CONCLUSIONS: Mercaptobenzothiazole is the preferential screening allergen for mercapto compounds because of the following: (1) greater proportion of missed reactions with MM; (2) greater proportion of doubtful/mild reactions in the missed group for MM; and (3) in the group positive to both, the low rate (2%) of moderate/strong reactions to MM and doubtful/mild reactions to MBT as compared with the converse (21%). Mercapto mix may be useful in an auxiliary rubber series.