Data linkage of two national databases: lessons learned from linking the Dutch Arthroplasty Register with the Dutch Foundation for Pharmaceutical Statistics

Background: To provide guidance on data linkage in case of non-unique identifiers, we present a case study linking the Dutch Foundation for Pharmaceutical Statistics and Dutch Arthroplasty Register to investigate opioid prescriptions before/after arthroplasty. Methods: Deterministic data linkage was used. Records were linked on: sex, birthyear, postcode, surgery date, or thromboprophylaxis initiation as a proxy for the surgery date. Different postcodes were used, depending on availability: patient postcode (available from 2013 onwards), hospital postcode with codes for physicians/hospitals, and hospital postcode with catchment area. Linkage was assessed in several groups: linked arthroplasties, linked on patient postcode, linked on patient postcode, and low-molecular-weight heparin(LWMH). Linkage quality was assessed by checking prescriptions after death, antibiotics after revision for infection, and presence of multiple prostheses. Representativeness was assessed by comparing the patient-postcode-LMWH group with the remaining arthroplasties. External validation was performed by comparing our opioid prescription rates with those derived from datasets from Statistics Netherlands. Results: We linked 317,899 arthroplasties on patient postcode/hospital postcode(48%). Linkage on the hospital postcode appeared insufficient. Linkage uncertainty ranged from roughly 30% in all arthroplasties to 10-21% in the patient-postcode-LMWH-group. This subset resulted in 166.357(42%) linked arthroplasties after 2013 with somewhat younger age, fewer females, and more often osteoarthritis than other indications compared to the other arthroplasties. External validation showed similar increases in opioid prescription rates. Conclusions: After identifier selection, checking data availability and internal validity, assessing representativeness, and externally validating our results we found sufficient linkage quality in the patient-postcode-LMWH-group, which consisted of around 42% of the arthroplasties performed after 2013.Orthopaedics, Trauma Surgery and Rehabilitatio

Capturing essential physiological aspects of interacting cartilage and bone tissue with osteoarthritis pathophysiology: a human osteochondral unit-on-a-chip model

Given the multi-tissue aspects of osteoarthritis (OA) pathophysiology, translation of OA susceptibility genes towards underlying biological mechanism and eventually drug target discovery requires appropriate human in vitro OA models that incorporate both functional bone and cartilage tissue units. Therefore, a microfluidic chip is developed with an integrated fibrous polycaprolactone matrix in which neo-bone and cartilage are produced, that could serve as a tailored human in vitro disease model of the osteochondral unit of joints. The model enables to evaluate OA-related environmental perturbations to (individual) tissue units by controlling environmental cues, for example by adding biochemical agents. After establishing the co-culture in the system, a layer of cartilaginous matrix is deposited in the chondrogenic compartment, while a bone-like matrix is deposited between the fibers, indicated by both histology and gene expression levels of collagen type 2 and osteopontin, respectively. As proof-of-principle, the bone and cartilaginous tissue are exposed to active thyroid hormone, creating an OA disease model. This results in increased expression levels of hypertrophy markers integrin-binding sialoprotein and alkaline phosphatase in both cartilage and bone, as expected. Altogether, this model could contribute to enhanced translation from OA risk genes towards novel OA therapies.Molecular Epidemiolog

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

Quantitative Dixon MRI sequences to relate muscle atrophy and fatty degeneration with range of motion and muscle force in brachial plexus injury

Development and application of statistical models for medical scientific researc

Does acromioplasty result in favorable clinical and radiologic outcomes in the management of chronic subacromial pain syndrome? A double-blinded randomized clinical trial with 9 to 14 years' follow-up

Orthopaedics, Trauma Surgery and Rehabilitatio

Out-of-hospital opioid prescriptions after knee and hip arthroplasty: prescribers and the first prescribed opioid

Background: We determined the first prescribed opioid and the prescribers of opioids after knee and hip arthroplasty (KA/HA) between 2013 and 2018 in the Netherlands. We also evaluated whether the first prescribed opioid dose was associated with the total dispensed dose and long-term opioid use in the first postoperative year.Methods: The Dutch Foundation for Pharmaceutical Statistics was linked to the Dutch Arthroplasty Register. Stratified for KA/HA, the first out-of-hospital opioid within 30 days of operation was quantified as median morphine milligram equivalent (MME). Opioid prescribers were orthopaedic surgeons, general practitioners, rheumatologists, anaesthesiol-ogists, and other physicians. Long-term use was defined as >= 1 opioid prescription for >90 postoperative days. We used linear and logistic regression analyses adjusted for confounders.Results: Seventy percent of 46 106 KAs and 51% of the 42 893 HAs were prescribed >= 1 opioid. Oxycodone increased as first prescribed opioid (from 44% to 85%) whereas tramadol decreased (64-11%), but their dosage remained stable (stronger opioids were preferred by prescribers). An increase in the first prescription of 1% MME resulted in a 0.43%/0.37% increase in total MME (KA/HA, respectively). A 100 MME increase in dose of the first dispensed opioid had a small effect on long-term use (prevalence: 25% KA, 20% HA) (odds ratio=1.02/1.01 for KA/HA, respectively). Orthopaedic surgeons increasingly prescribed the first pre-scription between 2013 and 2018 (44-69%). General practitioners mostly prescribed consecutive prescriptions (>50%).Conclusion: Oxycodone increased as first out-of-hospital prescription between 2013 and 2018. The dose of the first prescribed opioid was associated with the total dose and a small increased risk of prolonged use. First prescriptions were mostly written by orthopaedic surgeons and consecutive prescriptions by general practitioners

Opioid prescribing patterns after arthroplasty of the knee and hip: a Dutch nationwide cohort study from 2013 to 2018

Background and purpose - Numbers on opioid prescriptions over time in arthroplasty patients are currently lacking. Therefore we determined the annual opioid prescribing rate in patients who received a hip/knee arthroplasty (HA/KA) between 2013 and 2018.Patients and methods - The Dutch Foundation for Pharmaceutical Statistics, which provides national coverage of medication prescriptions, was linked to the Dutch Arthroplasty Register, which provides arthroplasty procedures. The opioid prescription rates were expressed as the number of defined daily dosages (DDD) and morphine milligram equivalent (MME) per person year (PY) and stratified for primary and revision arthroplasty. Amongst subgroups for age (= 1 opioid within the first year; this increased to 89% in 2018. For primary HA these numbers increased from 38% to 75%. In KAs the prescription rates increased from 13.1 DDD/PY to 14.4 DDD/PY, mainly due to oxycodone prescriptions (2.9 DDD/PY to 7.3 DDD/PY), while tramadol decreased (7.3 DDD/ PY to 4.6 DDD/PY). The number of MME/PY also increased (888 MME/PY to 1224 MME/PY). Similar changes were observed for HA and revision arthroplasties. Irrespective of joint, prescription of opioid medication increased over time, with highest levels in groups with preoperative opioid prescriptions while weak opioid prescriptions decreased.Interpretation - In the Netherlands, between 2013 and 2018 postoperative opioid prescriptions after KA and HA increased, mainly due to increased oxycodone prescriptions with highest levels after surgeries with preoperative prescriptions.Orthopaedics, Trauma Surgery and Rehabilitatio