Variant type and position predict two distinct limb phenotypes in patients with GLI3-mediated polydactyly syndromes.

INTRODUCTION: Pathogenic DNA variants in the GLI-Kruppel family member 3 (GLI3) gene are known to cause multiple syndromes: for example, Greig syndrome, preaxial polydactyly-type 4 (PPD4) and Pallister-Hall syndrome. Out of these, Pallister-Hall is a different entity, but the distinction between Greig syndrome and PPD4 is less evident. Using latent class analysis (LCA), our study aimed to investigate the correlation between reported limb anomalies and the reported GLI3 variants in these GLI3-mediated polydactyly syndromes. We identified two subclasses of limb anomalies that relate to the underlying variant. METHODS: Both local and published cases were included for analysis. The presence of individual limb phenotypes was dichotomised and an exploratory LCA was performed. Distribution of phenotypes and genotypes over the classes were explored and subsequently the key predictors of latent class membership were correlated to the different clustered genotypes. RESULTS: 297 cases were identified with 127 different variants in the GLI3 gene. A two-class model was fitted revealing two subgroups of patients with anterior versus posterior anomalies. Posterior anomalies were observed in cases with truncating variants in the activator domain (postaxial polydactyly; hand, OR: 12.7; foot, OR: 33.9). Multivariate analysis supports these results (Beta: 1.467, p=0.013 and Beta: 2.548, p<0.001, respectively). Corpus callosum agenesis was significantly correlated to these variants (OR: 8.8, p<0.001). CONCLUSION: There are two distinct phenotypes within the GLI3-mediated polydactyly population: anteriorly and posteriorly orientated. Variants that likely produce haploinsufficiency are associated with anterior phenotypes. Posterior phenotypes are associated with truncating variants in the activator domain. Patients with these truncating variants have a greater risk for corpus callosum anomalies.

A Secondary Analysis of Longitudinal Prevalence Data to Determine the Use of Pressure Ulcer Preventive Measures in Dutch Nursing Homes, 2005-2014.

Pressure ulcers (PUs) are an important and distressing problem in Dutch nursing homes. A secondary analysis of longitudinal data from the Dutch National Prevalence Measurement of Care Problems (LPZ) - an annual, multicenter, point-prevalence survey - was conducted for the years 2005-2014 to determine the use of specific recommended PU preventive measures from the European Pressure Ulcer Advisory Panel 1998, the National Pressure Ulcer Advisory Panel/European Pressure Ulcer Advisory Panel 2009, and the 2002 and 2011 Dutch PU guidelines. Preventive care was investigated among nursing home residents at risk for PUs and included skin care (moisturization); nutritional and hydration status assessment and optimization; and pressure redistribution involving mattresses, cushions, and heel pressure-relieving strategies and devices. Following abstraction from the study database, data for 3 at-risk groups were distinguished: 1) residents with a Braden score of 17, 18, or 19; 2) residents with a Braden score below 17; and 3) residents with a PU. Data were aggregated at the institutional level. Differences were tested with multiple regression analyses. The mean number of residents over the study period was 5435, the mean age was 82.8 years, and the mean Braden score was 15.3. None of the recommended preventive measures from the guidelines consulted was applied 100% of the time: preventive skin care measures were used in 25.1% to 63.8% of cases and dehydration and/or malnutrition were identified and managed in 27.8% to 65.6% of patients. Pressure redistribution with special types of mattresses was used in 85.2% of patients, cushions in (wheel)chairs were used in 64.8% of patients, and heels were offloaded in 57.8% of patients. The results regarding repositioning for the 3 groups, respectively, showed a maximum use of 9.7%, 30.3%, and 65.6%; the higher the PU risk, the more preventive measures were used. Although the results show a decrease in the percent of category 2 through category 4 PUs from 16.6% to 5.5% and a trend toward increased use of preventive measures (more skin care, attention for dehydration/malnutrition, use of floating heels/heel devices, and pressure-relieving systems when a PU was present), the reason why measurements were suboptimally used remains unclear. Further research to address the application of guidelines in daily practice is needed.

Quality of measurements of acute surgical and traumatic wounds using a digital wound-analysing tool.

The aim of this study was to assess the reliability of measurements using a wound-analysing tool and their interpretability. Wound surface areas and tissue types, such as granulation, slough and necrosis, in twenty digital photographs were measured using a specific software program. The ratio of these tissue types in a wound was calculated using a wound profile. We calculated the intraclass coefficient or κ for reliability, standard error of measurement (SEM) and smallest detectable change (SDC). The inter-rater reliability intraclass correlation coefficient (ICC) was 0·99 for surface area, 0·76 for granulation, 0·67 for slough and 0·22 for necrosis. The profiles gave an overall κ of 0·16. For test-retest reliability, the ICC was 0·99 for surface area, 0·81 for granulation, 0·80 for slough and 0·97 for necrosis. The agreement of the applied profiles in the test-retest was 66% (40-100). SEM and SDC for surface area were 0·10/0·27; for granulation, 6·88/19·08; for slough, 7·17/19·87; and for necrosis, 0·35/0·98, respectively. Measuring wound surface area and tissue types by means of digital photo analysis is a reliable and applicable method for monitoring wound healing in acute wounds in daily practice as well as in research.

Dupuytren's contracture: a retrospective database analysis to determine hospitalizations in the Netherlands.

BACKGROUND: Dupuytren's contracture is a condition of the palmar fascia involving contractures of the fascia and skin in the hand. Current treatment for Dupuytren's contracture is mainly limited to surgery. In the Netherlands, little is known about the prevalence of Dupuytren's contracture. In this study we determined the prevalence of patients with a hospitalization for Dupuytren's contracture in the Netherlands and characterized their (re)hospitalizations. METHODS: From the PHARMO database, which consists of multiple observational databases linked on a patient level, all patients hospitalized for Dupuytren's contracture between 2004 and 2007 were included in the source population (ICD-9-CM code 728.6). Numbers from this source population were used to provide estimates of hospitalizations for Dupuytren's contracture in the Netherlands. Patients with a medical history in the PHARMO database of at least 12 months before their hospitalization were included in the study cohort and followed until end of data collection, death, or end of study period, whichever occurred first. Type of admission, length of stay, recorded procedures, treating specialty, number of rehospitalizations for Dupuytren's contracture, and time to first rehospitalization were assessed. RESULTS: Of 3, 126 patients included in the source population, 3, 040 were included in the study population. The overall prevalence of patients with a hospitalization for Dupuytren's contracture was 0.04%, with the highest prevalence (0.25%) among 60-79 year old males. The majority (85%) of all hospitalizations were day-case admissions. Of the admitted inpatients (15%) the majority (81%) had one overnight stay in the hospital. The most common recorded procedure was fasciectomy (87%) and 78% of patients was treated by a plastic surgeon. During a median (IQR) follow-up of 2.9 (1.8-4.0) years, 523 patients were rehospitalized for Dupuytren's contracture. The median (IQR) time to first rehospitalization was 0.8 (0.4-1.9) years. CONCLUSIONS: This study is a first exploration of Dupuytren's contracture in the Netherlands based on hospitalizations, showing a prevalence of 0.25% among 60-79 year old males. Future studies should also address outpatient procedures to get a complete picture of the treatment of Dupuytren's contracture. In addition, patients not yet treated should be included to be able to estimate the prevalence of Dupuytren's contracture.