The molecular aetiology of haemophilia A in a New Zealand patient group

The genetic basis of haemophilia A (HA) is well-established, and many haematology services are supported by molecular biology laboratories that offer factor VIII genetic testing for HA patients. This report describes the results from factor VIII gene (F8) analysis of a New Zealand cohort of 45 proband HA patients. We screened all proband HA patients attending local clinics to determine the molecular basis of disease in each case. We also aimed to evaluate the significance of founder effect in this population and to explain an unusual case of HA in a female patient. HA patients were screened for the common F8 gene inversion mutations using previously described PCR-based techniques, and for single base substitution mutations using denaturing high performance liquid chromatography and DNA sequencing. Analysis of microsatellite markers located within or near F8 was used to determine identity by descent and trace inheritance patterns of disease alleles. X-chromosome inactivation (XCI) patterns were detected using methylation specific PCR. Pathogenic F8 gene mutations were detected in all 45 HA patients in this cohort and non-random XCI was confirmed in a female haemophiliac. We report nine novel F8 mutations, including two splicing mutations, a five nucleotide deletion and a large deletion at the 5' end of the gene. The molecular aetiology of HA was similar to that described in other studies but the distribution of mutations was unusual due to founder effects, with almost a quarter of all probands being descended from just three individuals.     

Drinking and Alcohol-Related Harm Among New Zealand University Students: Findings From a National Web-Based Survey

Background: Alcohol‐related harm is pervasive among college students in the United States of America and Canada, where a third to half of undergraduates binge drink at least fortnightly. There have been no national studies outside North America. We estimated the prevalence of binge drinking, related harms, and individual risk factors among undergraduates in New Zealand. Methods: A web survey was completed by 2,548 undergraduates (63% response) at 5 of New Zealand’s 8 universities. Drinking patterns and alcohol‐related problems in the preceding 4 weeks were measured. Drinking diaries for the preceding 7 days were completed. Multivariate analyses were used to identify individual risk factors. Results: A total of 81% of both women and men drank in the previous 4 weeks, 37% reported 1 or more binge episodes in the last week, 14% of women and 15% of men reported 2+ binge episodes in the last week, and 68% scored in the hazardous range (4+) on the AUDIT consumption subscale. A mean of 1.8 (95% confidence interval 1.4, 2.3) distinct alcohol‐related risk behaviors or harmful consequences were reported, e.g., 33% had a blackout, 6% had unprotected sex, and 5% said they were physically aggressive toward someone, in the preceding 4 weeks. Drink‐driving or being the passenger of a drink‐driver in the last 4 weeks was reported by 9% of women and 11% of men. Risk factors for frequent binge drinking included: lower age, earlier age of drinking onset, monthly or more frequent binge drinking in high school, and living in a residential hall or a shared house (relative to living with parents). These correlates were similar to those identified in U.S. and Canadian studies. Conclusions: Strategies are needed to reduce the availability and promotion of alcohol on and around university campuses in New Zealand. Given the high prevalence of binge drinking in high school and its strong association with later binge drinking, strategies aimed at youth drinking are also a priority. In universities, high‐risk drinkers should be identified and offered intervention early in their undergraduate careers.     

Systemic lupus erythematosus (SLE) at the Kenyatta National Hospital

Systemic lupus erythematosus (SLE) is a complex disease with varied clinical presentation and autoantibody production. It has previously been reported as rare in Black Africans. We established a Rheumatology clinic at the Kenyatta National Hospital in April 2010, and a 1 year audit of this clinic was carried out in September 2011. This is a report of this audit of patients who met the American College of Rheumatology (ACR) criteria for SLE. Thirteen patients met the ACR criteria; their mean age was 34 years, and they were all female. The commonest manifestations were malar rash and arthritis in 69.2 %. Antinuclear antibody was present in 79.6 %, and anti-dsDNA was present in 38.5 %. None of them had human immunodeficiency virus infection; 30 % had other comorbidities (hypertension, diabetes, and renal failure). Thirty percent also had an infection during this period. All these 13 were on prednisolone and 92 % of them were on hydroxychloroquine. There was no reported death during the study period. This confirms the presence of SLE in patients in Kenya who meet the ACR criteria.     

New onset of venous thromboembolism among hospitalized patients at Brigham and Women's Hospital is caused more often by prophylaxis failure than by withholding treatment

CONTEXT: Guidelines to prevent venous thromboembolism (VTE) have been widely distributed and generally have been assumed to be effective. Therefore, among hospitalized patients, the development of VTE is thought to occur in the context of omitted prophylaxis. OBJECTIVES: To describe hospitalized patients who develop VTE and to determine whether they received antecedent prophylaxis. DESIGN: Case series. SETTING: Brigham and Women's Hospital. PATIENTS: Three hundred eighty-four patients who developed in-hospital deep venous thrombosis or pulmonary embolism or who developed VTE within 30 days of prior hospital discharge. Main outcome measures: The relationship of developing new-onset VTE to the use or omission of antecedent in-hospital prophylaxis. RESULTS: Of the 384 identified patients, 272 had deep venous thrombosis alone, 62 had pulmonary embolism alone, and 50 had deep venous thrombosis and pulmonary embolism. Most were medical service patients; fewer than one fourth were general or orthopedic surgery patients. Overall, 52% had received antecedent VTE prophylaxis. Thirteen deaths (3.4%) were ascribed to pulmonary embolism, and prophylaxis was omitted in only 1 of those 13 patients. CONCLUSIONS: Most deaths from pulmonary embolism among patients hospitalized for other conditions occurred in the setting of failed prophylaxis rather than omitted prophylaxis. High-risk patients, especially medical service patients, warrant intensive VTE prophylaxis and close follow-up to ensure successful outcomes.     

Surveillance for Dysplasia in Patients With Inflammatory Bowel Disease: A National Survey of Colonoscopic Practice in New Zealand

BACKGROUND Patients with chronic ulcerative colitis and Crohns colitis have an increased risk of colorectal cancer. Because of this, surveillance colonoscopy is practiced.AIMS We aimed to describe the practice of surveillance colonoscopy in New Zealand, with comparison among specialties, and with practice internationally.SUBJECTS New Zealand colonoscopists (both physicians and surgeons) looking after patients with inflammatory bowel disease were surveyed to evaluate attitudes about surveillance colonoscopy and ways in which colonoscopy results are interpreted.METHODS A postal survey assessed the colonoscopists understanding of how and why surveillance colonoscopy is undertaken and their interpretation of the results from such evaluations.RESULTS Of the196 physicians and surgeons surveyed, 180 responded (92 percent). Sixty responses were excluded. Only 24 of 120 respondents (20 percent) correctly defined dysplasia. The median number of biopsies taken at colonoscopy was 17. Eighty of 120 (67 percent) and 77 of 120 (64 percent) doctors underestimate the risk of invasive malignancy if low-grade or high-grade dysplasia, respectively, is identified. The colectomy referral rate for dysplasia-associated lesion or mass was 115/120 (96 percent); that for high-grade dysplasia was 110/120 (92 percent); and that for low-grade dysplasia was 26/120 (22 percent). Thirty of 120 (25 percent) doctors offer patients the option of colectomy after 20 years of colitis. Seventy of 120 (58 percent) doctors sought the opinion of a second pathologist if dysplasia was found. There were differences in responses between specialist groups, with colorectal surgeons most likely to correctly define dysplasia and appreciate the significance of low-grade dysplasia.CONCLUSIONS Many New Zealand colonoscopists have a poor understanding of the definition and importance of dysplasia associated with colitis. Although colectomy referral rates are higher in this study than in similar studies, low-grade dysplasia is often not referred for colectomy. Improved education may improve surveillance practice.Presented at the New Zealand Society of Gastroenterology Annual Scientific Meeting, Auckland, New Zealand, November 13 to 15, 2002 and at the Royal Australasian College of Surgeons Annual Scientific Meeting, Brisbane, Queensland, Australia, May 5 to 9, 2003.Supported by a grant from the Canterbury Medical Research Foundation.