Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.

Willingness to pay to assess patient preferences for therapy in a Canadian setting.

BACKGROUND: Adult outpatient parenteral antibiotic therapy (OPAT) programs have been reported in the literature for over 20 years, however there are no published reports quantifying preference for treatment location of patients referred to an OPAT program. The purpose of this study was to elicit treatment location preferences and willingness to pay (WTP) from patients referred to an OPAT program. METHODS: A multidisciplinary, single centre, prospective study at a 1000-bed Canadian adult tertiary care teaching hospital. This study involved a WTP questionnaire that was administered over a 9-month study period. Eligible and consenting patients referred to the OPAT program were asked to state their preference for treatment location and WTP for a hypothetical treatment scenario involving intravenous antibiotic therapy. Multiple linear regression analysis was performed to determine predictors of WTP. RESULTS: Of 131 eligible patients, 91 completed the WTP questionnaire. The majority of participants were males, married, in their sixth decade of life and had a secondary school education or greater. The majority of participants were retired or they were employed with annual household incomes less than 60,000 dollars. Osteomyelitis was the most common type of infection for which parenteral therapy was required. Of those 87 patients who indicated a preference, 77 (89%) patients preferred treatment at home, 10 (11%) patients preferred treatment in hospital. Seventy-one (82%) of these patients provided interpretable WTP responses. Of these 71 patients, 64 preferred treatment at home with a median WTP of 490 dollars CDN (mean 949 dollars, range 20 to 6250 dollars) and 7 preferred treatment in the hospital with a median WTP of 500 dollars CDN (mean 1123 dollars, range 10 to 3000 dollars). Tests for differences in means and medians revealed no differences between WTP values between the treatment locations. The total WTP for the seven patients who preferred hospital treatment was 7,859 dollars versus 60,712 dollars for the 64 patients who preferred home treatment. Income and treatment location preference were independent predictors of WTP. CONCLUSION: This study reveals that treatment at home is preferred by adult inpatients receiving intravenous antibiotic therapy that are referred to our OPAT program. Income and treatment location appear to be independently associated with their willingness to pay.

Quality-of-life assessment in an outpatient parenteral antibiotic program.

OBJECTIVE: To measure changes and to identify predictors of change of health-related quality of life (HRQoL) for enrollees into an outpatient parenteral antibiotic therapy (OPAT) program. METHODS: A multidisciplinary, single-center, prospective investigation was conducted at a 1000-bed Canadian adult tertiary-care teaching hospital. Over a 15-month study period, consenting patients who were enrolled in the OPAT program completed paired Short Form-36 (SF-36) questionnaires within 48 hours prior to discharge from the hospital and again 26-30 days after discharge. Sociodemographic data and clinical variables were also collected for the purpose of determining potential predictors of change in quality of life. RESULTS: During the study period, 134 patients were enrolled in the OPAT program and 82 completed the paired SF-36 questionnaires. Study participants experienced a significant improvement in 3 SF-36 domains (physical functioning, bodily pain, role emotional) and the mental component summary scale (MCS) scores when they were transferred from the hospital to home setting. The SF-36 scores for all domains and summary scales were lower than the Canadian population average (all p < 0.001). Multiple linear-regression analysis revealed that infectious disease diagnosis and baseline physical component summary scale (PCS) scores were predictors of the change in the PCS score when patients transferred from the hospital to the home setting. Length of hospital stay and baseline MCS scores were predictors of the change in MCS scores when patients transferred from the hospital to the home setting. CONCLUSIONS: This study reveals that some domains in HRQoL appear to improve 4 weeks after discharge for adults enrolled in an OPAT program and that there are different predictors for changes in physical and mental health.