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Summary Objective Untreated Cushing's syndrome (CS) is associated with significant morbidity and mortality. However, recent operative series suggest low morbidity and mortality for CS, whereas population-based surveys report elevated mortality rates. We investigated the mortality and morbidity of CS in New Zealand. Design A nationwide retrospective survey of patients with CS between 1960 and 2005 managed at the four main endocrinology services. Patients A total of 253 patients with CS were identified, excluding adrenal carcinoma and malignant ectopic CS. Measurements The primary outcome was the standardized mortality ratio (SMR), comparing the observed number of deaths with the expected number for the population matched for age, sex and duration of follow-up. Secondary outcomes were the change in prevalence of co-morbidities at presentation and at final follow-up. Results The approximate prevalence and incidence of CS was 79/million and 1·8/million/y. The mean age at presentation was 39 year, and median duration of follow-up was 6·4 year (range 0-46). Overall, 89% achieved biochemical cure at last follow-up, with >90% achieving biochemical cure for CS from adrenal adenoma and pituitary causes. Thirty-six patients died during follow-up compared with 8·8 expected deaths (SMR 4·1, 95%CI 2·9-5·6). While hypertension, sexual dysfunction, myopathy and mild psychiatric illness were significantly reduced after treatment, hypertension, diabetes mellitus, moderate or major psychiatric illness, and osteoporosis were common at final follow-up. Conclusion CS is associated with both high mortality and a high prevalence of co-morbidities, even when biochemical cure rates are between 80% and 90%. [ABSTRACT FROM AUTHOR]

Genetic factors play an important role in the pathogenesis of Paget disease of bone (PDB). SQSTM1 is the most important disease-associated gene identified to date. We investigated the relationship of family history, phenotype, and SQSTM1 mutation status in New Zealand (a country with a high prevalence of PDB) in patients with a family history and/or a severe phenotype. We studied 61 unrelated subjects with familial PDB. Family history was subclassified into three groups according to the closeness of the relationship. We also studied a fourth group of 19 unrelated patients defined by early onset and/or severe disease but no family history. The PDB phenotype was defined according to age, alkaline phosphatase activity, and disease extent on scintiscan at the time of diagnosis. Mutations in exon 8 of SQSTM1 were detected by screening of genomic DNA. Four different mutations were identified; the ubiquitous P392L mutation and the truncating mutation E396X accounted for 89% of cases. Overall 26% of patients with familial PBD in New Zealand had disease-associated mutations in the SQSTM1 gene. Mutations were most prevalent (60%) in those with a parent or sibling and at least one other relative affected (P < 0.002). The severity of the phenotype was significantly related to SQSTM1 mutation status but not the strength of the family history (P < 0.005). SQSTM1 mutations were found in 10.5% of patients with early onset and/or severe disease but no family history. [ABSTRACT FROM AUTHOR]

Background: Severe prolonged vitamin D deficiency can cause rickets or osteomalacia. Both can be prevented by sunshine exposure or vitamin D supplementation. Although New Zealand guidance does not recommend vitamin D supplementation for the general population, it can be considered for individuals at risk of vitamin D deficiency. Routine measurement of 25-hydroxyvitamin D (25OHD) is also considered unnecessary., Methods: We investigated the rates of vitamin D supplementation, rickets and osteomalacia in New Zealand, and of 25OHD results in Auckland, over the last two decades., Results: Vitamin D prescriptions increased 14-fold, from 86,295/year to 1,215,507/year, between 2003 and 2019, with medication costs alone in 2019 being >$1 million. Despite these changes, the annual prevalence of hospital admissions for rickets, osteomalacia and unspecified vitamin D deficiency remained low and stable (10-20/year). 25OHD concentrations increased between 2002 and 2003 and between 2009 and 2019, and in the later time-period, 25OHD tests mainly identified individuals without vitamin D deficiency (40-50% >75nmol/L, 65-70% >50nmol/L and only 7-12.5% <25nmol/L)., Conclusions: Osteomalacia and rickets persist at low rates despite widespread, increasingly costly vitamin D supplementation and testing, which largely identifies individuals without vitamin D deficiency. These results suggest that vitamin D guidance and practice in New Zealand should change., Competing Interests: None of the authors have any financial conflicts of interest, but all authors have co-authored randomised controlled trials and systematic reviews of the efficacy of vitamin D supplements and co-authored articles concluding that there is no role for routine vitamin D supplementation in community dwelling individuals.

A patient with a long-standing medical condition was enrolled in a clinical trial, deemed as conducted for the benefit of the manufacturer. The patient entered the trial and, shortly afterward, developed a severe illness that left him with a significant permanent disability. Clinical investigators and clinicians not involved in the trial believed the illness was related to trial participation. Because the trial was for the manufacturer's benefit, the participant was not eligible for compensation from the Accident Compensation Corporation (ACC). Discussions with the trial sponsor took many years to resolve. This case highlights the numerous barriers faced by patients seeking compensation from trial sponsors for adverse events probably resulting from trial participation. Legal changes are required to resolve this situation. Without such changes, potential participants and researchers should consider carefully whether to participate and invite people to participate in trials conducted for the benefit of a manufacturer, as there may be little support available should a trial-related illness occur., Competing Interests: Dr Bolland reports: I have no financial conflicts to declare. The views expressed in the article represent my own opinion: the manuscript has not been written on behalf of any of my employers, nor does it represent the views of any of my employers.

Aims: Researchers are commonly requested to describe potential benefits of their research for New Zealand in funding applications, but such benefits can be difficult to precisely determine. Recently, we reported that calcium supplements increase cardiovascular risk. We investigated the impact of this research on prescriptions of calcium supplements in New Zealand., Methods: Data on the number of calcium supplement prescriptions in New Zealand from 2000-2012 were obtained from the Ministry of Health and the total costs of calcium carbonate from PHARMAC., Results: Calcium prescriptions increased rapidly between 2000 and 2007, plateaued after the publication of a randomised controlled trial in 2008, and then rapidly declined after publication of a meta-analysis in 2010. Since 2007, monthly prescriptions have decreased by 66%. From 2000 to 2006, the annual cost of calcium carbonate increased from $1.2 to $2.4 million, but from 2007 to 2012, the annual cost decreased by $1.5 million, with a cumulative reduction in cost of $3.9 million. There were substantial regional variations in declines in prescription numbers, and in 2012 prescribing rates., Conclusion: Public-good funding of independent researchers to conduct randomised clinical trials with meaningful clinical outcomes and meta-analyses of such trials can translate into substantial benefits through cost savings.