Hypophosphatasia (HPP) is a rare inherited disease caused when the body does not produce enough of an enzyme that enables calcium and phosphate to bind together to strengthen bones and teeth. When the enzyme is missing or at low levels, bones and teeth are weak and may not grow properly, with effects not only the skeleton, but also breathing and brain development; also, unused calcium and phosphate can accumulate in the body, damaging the kidneys and other body systems. The severity of HPP is generally related to the age at which the disease became apparent: the form diagnosed at or before birth can be fatal, while forms diagnosed in adults and older children are milder. We wish to use the Clinical Practice Research Datalink to estimate the number of cases of HPP in the UK at 30 June 2015 and to describe HPP's effects on patients' health and use of healthcare services. These findings will be important in understanding the public health impact of HPP.
We aim to estimate the prevalence of hypophosphatasia (HPP) in a UK population based on CPRD and to characterize its epidemiology in terms of healthcare-resource use, mortality and morbidity. Patients will be included based on two algorithms: one based on diagnostic codes (Read or ICD-10); the other also including patients with low alkaline phosphatase levels, and will be ascribed suspected or uncertain HPP status accordingly. Main analyses will consider suspected HPP cases, with sensitivity analyses performed on all cases and those eligible for linkage to HES and ONS mortality data. Period prevalence will be calculated for 2015, based on patients registered with an up-to-standard practice at 30 June 2015. Clinical manifestations will be determined in CPRD GOLD by Read codes and test results and in HES by ICD-10 and OPCS codes. Deaths and causes of death will be ascertained from CPRD GOLD and ONS data. Frequency of healthcare use, as primary-care contacts, inpatient episodes, outpatient attendances, and prescriptions issued in primary care, will be calculated. Results will be tabulated with wide granularity, ensuring that cells with n<5 are suppressed in accordance with CPRD guidelines to prevent deductive/unintentional disclosure.
Prevalence of hypophosphatasia; All-cause mortality and causes of death; NHS resource use associated with hypophosphatasia; Prevalence and incidence of depression and anxiety in hypophosphatasia; Clinical manifestations of hypophosphatasia.
Christopher Morgan - Chief Investigator - Pharmatelligence Limited t/a Human Data Sciences
Sara Jenkins-Jones - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
Richard Eastell - Collaborator - University of Sheffield
Sara Jenkins-Jones - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data