Natural History of Keloids: A Sociodemographic Analysis Using Structured and Unstructured Data.

INTRODUCTION: Keloids are lesions characterized by the growth of dense fibrous tissue extending beyond original wound boundaries. Research into the natural history of keloids and potential differences by sociodemographic factors in the USA is limited. This real-world, retrospective cohort study aimed to characterize a population of patients with keloids compared with matched dermatology and general cohorts. METHODS: Patients with ≥ 2 International Classification of Diseases codes for keloid ≥ 30 days apart and a confirmed keloid diagnosis from clinical notes enrolled in the OM1 Real-World Data Cloud between 1 January 2013 and 18 March 2022 were age- and sex-matched 1:1:1 to patients without keloids who visited dermatologists ("dermatology cohort") and those who did not ("general cohort"). Results are presented using descriptive statistics and analysis stratified by cohort, race, ethnicity, household income, and education. RESULTS: Overall, 24,453 patients with keloids were matched to 23,936 dermatology and 24,088 general patients. A numerically higher proportion of patients with keloids were Asian or Black. Among available data for patients with keloids, 67.7% had 1 keloid lesion, and 68.3% had keloids sized 0.5 to < 3 cm. Black patients tended to have larger keloids. Asian and Black patients more frequently had > 1 keloid than did white patients (30.6% vs. 32.5% vs. 20.5%). Among all patients with keloids who had available data, 56.4% had major keloid severity, with major severity more frequent in Black patients. Progression was not significantly associated with race, ethnicity, income, or education level; 29%, 25%, and 20% of the dermatology, keloid, and general cohorts were in the highest income bracket (≥ US$75,000). The proportion of patients with income below the federal poverty line (< US$22,000) and patterns of education level were similar across cohorts. CONCLUSION: A large population of patients in the USA with keloids was identified and characterized using structured/unstructured sources. A numerically higher proportion of patients with keloids were non-white; Black patients had larger, more severe keloids at diagnosis.

24-hour urine oxalate and risk of chronic kidney disease.

BACKGROUND: To assess whether 24-hr urine oxalate (UOx) excretion is a risk factor for incident chronic kidney disease (CKD). METHODS: This longitudinal observational US-based study included 426,896 individuals age ≥ 18 years with no CKD at baseline and with at least one UOx and at least 6 months of baseline and 6 months of follow-up data. Of these, 11,239 (2.6%) had an underlying malabsorptive condition. Incident CKD, defined by relevant ICD codes, was identified from a multi-source data cloud containing individual-level healthcare claims and electronic medical records data. The association between categories of UOx and incident CKD was modeled using logistic regression adjusting for age, sex, race, BMI, baseline urine calcium, urine citrate, urine volume, tobacco use, hypertension, diabetes, malabsorption, and cardiovascular disease. RESULTS: Mean follow-up time was 38.9 months (SD 21.7). Compared with individuals with UOx <20 mg/24-hr, the odds of developing incident CKD increased for UOx 20-29 mg/24-hr (multivariate-adjusted (MV) OR: 1.14, 95% CI: 1.07, 1.21) through 80+ mg/24-hr (MVOR: 1.35 [1.21, 1.50] and was statistically significant for each UOx category. A similar pattern was seen in the subgroup with a malabsorptive condition though the magnitudes of association were larger, with the odds of developing incident CKD increased for UOx 20-29 mg/24-hr (MVOR: 1.50 [1.03, 2.20] through 80+ mg/24-hr (MVOR: 2.34 [1.50, 3.63] as compared with UOx <20 mg/24-hr. CONCLUSIONS: The risk of incident CKD increases with increasing 24-hr urine oxalate excretion. Future studies should examine whether reducing urine oxalate diminishes the risk of developing CKD.

Association of sweat chloride concentration at time of diagnosis and CFTR genotype with mortality and cystic fibrosis phenotype.

BACKGROUND: The extent to which sweat chloride concentration predicts survival and clinical phenotype independently of CFTR genotype in cystic fibrosis is not well understood. METHODS: We analyzed the US Cystic Fibrosis Foundation Patient Registry data using Cox regression to examine the relationship between sweat chloride concentration (<60, 60-<80, ≥80mmol/L), CFTR genotype (high and lower risk for lung function decline), and survival and mixed linear regression to examine the relationship between sweat chloride, CFTR genotype, and measures of lung function and growth. RESULTS: When included in the same model, CFTR genotype, but not sweat chloride, was independently associated with survival and with lung function, height, and BMI. Among patients with unclassified CFTR genotype, sweat chloride was an independent predictor of survival (<60 HR 0.53 [0.37, 0.77], 60-<80 0.51 [0.42, 0.63]). CONCLUSIONS: Sweat chloride concentration may be a useful predictor of mortality and clinical phenotype when CFTR genotype functional class is unclassified.

Characterization of Missing Data in Clinical Registry Studies.

Patterns of missing data are seldom well-characterized in observational research. This study examined the magnitude of, and factors associated with, missing data across multiple observational studies. Missingness was evaluated for demographic, clinical, and patient-reported outcome (PRO) data from a procedure registry (TOPS), a rare disease (cystic fibrosis) registry (Port-CF), and a comparative effectiveness registry (glaucoma, RiGOR). Generalized linear mixed effects models were fit to assess whether patient characteristics or follow-up methods predicted missingness. Data from 156,707 surgical procedures, 32,118 cystic fibrosis patients, and 2373 glaucoma patients were analyzed. Data were rarely missing for demographics, treatments, and outcomes. Missingness for clinical variables varied by registry and measure and depended on whether a variable was required. Within RiGOR, PRO forms were missing more often when collected by e-mail compared with office-based paper data collection. In Port-CF, missingness varied based on insurance status and sex. Strategic consideration of operational approaches affecting missing data should be performed prior to data collection and assessed periodically during study conduct.

Recognizing true H5N1 infections in humans during confirmed outbreaks.

INTRODUCTION: The goal of this study was to evaluate whether any characteristics that are evident at presentation for urgent medical attention could be used to differentiate cases of H5N1 in the absence of viral testing. METHODOLOGY: Information about exposure to poultry, clinical signs and symptoms, treatments, and outcomes was abstracted from existing data in the global avian influenza registry (www.avianfluregistry.org) using standardized data collection tools for documented and possible cases of H5N1 infection who presented for medical attention between 2005-2011 during known H5N1 outbreaks in Azerbaijan, Indonesia, Pakistan and Turkey. RESULTS: Demography, exposure to poultry, and presenting symptoms were compared, with only the common symptoms of fever and headache presenting significantly more frequently in confirmed H5N1 cases than in possible cases. Reported exposure to  infected humans was also more common in confirmed cases. In contrast, unexplained respiratory illness, sore throat, excess sputum production, and rhinorrhea were more frequent in possible cases. Overall, oseltamivir treatment showed a survival benefit, with the greatest benefit shown in H5N1 cases who were treated within two days of symptom onset (51% reduction in case fatality). CONCLUSION: Since prompt treatment with antivirals conferred a strong survival benefit for H5N1 cases, presumptive antiviral treatment should be considered for all possible cases presenting during an outbreak of H5N1 as a potentially life-saving measure.

Human influenza A H5N1 in Indonesia: health care service-associated delays in treatment initiation.

BACKGROUND: Indonesia has had more recorded human cases of influenza A H5N1 than any other country, with one of the world's highest case fatality rates. Understanding barriers to treatment may help ensure life-saving influenza-specific treatment is provided early enough to meaningfully improve clinical outcomes. METHODS: Data for this observational study of humans infected with influenza A H5N1 were obtained primarily from Ministry of Health, Provincial and District Health Office clinical records. Data included time from symptom onset to presentation for medical care, source of medical care provided, influenza virology, time to initiation of influenza-specific treatment with antiviral drugs, and survival. RESULTS: Data on 124 human cases of virologically confirmed avian influenza were collected between September 2005 and December 2010, representing 73% of all reported Indonesia cases. The median time from health service presentation to antiviral drug initiation was 7.0 days. Time to viral testing was highly correlated with starting antiviral treatment (p < 0.0001). We found substantial variability in the time to viral testing (p = 0.04) by type of medical care provider. Antivirals were started promptly after diagnosis (median 0 days). CONCLUSIONS: Delays in the delivery of appropriate care to human cases of avian influenza H5N1 in Indonesia appear related to delays in diagnosis rather than presentation to health care settings. Either cases are not suspected of being H5N1 cases until nearly one week after presenting for medical care, or viral testing and/or antiviral treatment is not available where patients are presenting for care. Health system delays have increased since 2007.

Determinants of antiviral effectiveness in influenza virus A subtype H5N1.

BACKGROUND: Oseltamivir is widely used as treatment for influenza virus A subtype H5N1 (hereafter, "H5N1") infection but, like any intervention, is not always effective. METHODS: We used Avian Influenza Registry data from 10 countries to examine the risk of death in 215 patients with confirmed H5N1 infection who were treated with oseltamivir, according to viral clade, age, respiratory failure, and adjunctive treatment with corticosteroids or antibiotics. RESULTS: The median age of infected individuals was 18 years, and 50% were male. The highest fatality rate occurred in a country with clade 2.1 virus circulation, and the lowest occurred in countries with clade 2.2 virus circulation (P < .001). In univariate analyses, age of ≤5 years and treatment ≤2 days after symptom onset were protective against fatality. When accounting for all risk factors, early initiation of oseltamivir was found to be particularly effective in individuals without respiratory failure (odds ratio, 0.17; P = .04). Patients who had advanced respiratory failure requiring ventilatory support at the time of oseltamivir initiation were more likely to die from the episode of H5N1 infection than patients who did not (P < .001). Adjunctive therapy did not improve the likelihood of surviving the episode. CONCLUSIONS: Oseltamivir is especially effective for treating H5N1 infection when given early and before onset of respiratory failure. The effect of viral clade on fatality and treatment response deserves further investigation.

H5N1 avian influenza in children.

BACKGROUND: Avian influenza continues to pose a threat to humans and maintains the potential for greater transmissibility. Understanding the clinical presentation and prognosis in children will help guide effective diagnosis and treatment. METHODS: A global patient registry was created to enable systematic collection of clinical, exposure, treatment, and outcomes data on confirmed cases of H5N1. Bivariate and multivariate statistical tools were used to describe clinical presentation and evaluate factors prognostic of survival. RESULTS: Data were available from 13 countries on 193 children <18 years who were confirmed as having been infected with H5N1; 35.2% of cases were from Egypt. The case fatality rate (CFR) for children was 48.7%, with Egypt having a very low pediatric CFR. Overall, children aged ≤5 years had the lowest CFR and were brought to hospitals more quickly and treated sooner than older children. Children who presented for medical care with a complaint of rhinorrhea had a 76% reduction in the likelihood of death compared with those who presented without rhinorrhea, even after statistical adjustment for age, having been infected in Egypt, and oseltamivir treatment (P = .02). Delayed initiation of treatment with oseltamivir increases the likelihood of death, with an overall 75% increase in the adjusted odds ratio for death for each day of delay. CONCLUSIONS: The presence of rhinorrhea appears to indicate a better prognosis for children with H5N1, with most patients surviving regardless of age, country, or treatment. For individuals treated with oseltamivir, early initiation of treatment substantially enhances the chance of survival.