Pharmacology management of major neurocognitive disorders in the United Kingdom: a population-based drug utilization study
Bibliographic record
Abstract
Background: Major neurocognitive disorders (MNCD) affect 1 in 11 persons over age 65.Cholinesterase inhibitors (ChEIs, i.e. donepezil, galantamine, and rivastigmine) and memantine are the only approved drugs for the management of MNCD in both the United Kingdom (UK) and Canada.The objective of this thesis was to describe the sex, age, and clinical characteristics associated with MNCD drug utilization, and to examine how prescription patterns vary with these characteristics.Methods: I assembled a retrospective, population-based inception cohort of all patients aged 65+ years with a new diagnosis of MNCD between 1997 and 2017 in the Clinical Practice Research Datalink, a primary care database with 15 million patient records from over 700 primary care practices in the UK.Patients were followed from MNCD diagnosis until the date of departure from the general practitioner practice, death, or March 2017.MNCD drug utilization patterns included time from date of diagnosis to medication initiation, switches, adherence and persistence, which were described overall, by sex, age group (65-74, 75-84, 85-94, 95+) and MNCD subtype (Alzheimer's, vascular, mixed, other [dementia with Lewy bodies, frontotemporal and Parkinson's] and non-specific).Associations between patient characteristics and drug initiation, switches, discontinuation and non-adherence were compared using Cox proportional hazards regression models, presented as hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant demographic and clinical covariates.Results: A total of 91,025 patients with MNCD were identified, among whom 25,071 (28%) received at least 1 MNCD drug prescription during follow-up and 13% of initiators switched to a second MNCD drug.Persistence was low (82% after the first trial, 56% after 6 months, 19% after 2 years), and adherence was modest among those who were persistent (53% at 2 years).Compared to male patients, female patients were more likely to initiate treatment with donepezil (adjusted HR=1.10, 95% CI 1.07-1.14),less likely to discontinue treatment with donepezil (adjusted HR=0.96, 95% CI 0.93-0.99)and less likely to become non-adherent (adjusted HR=0.91, 95% CI 0.87-0.96) to donepezil treatment.As compared to patients diagnosed at age 65-74, those diagnosed over age 95 were more frequently prescribed memantine (28%, versus 9%), less likely to switch medications (adjusted HR=0.25, 95% CI 0.23-0.28),were less persistent and had a higher rate of non-adherence.There were observed differences among the 5 iii dementia subtypes with respect to MNCD treatment initiation, switches and persistence but not adherence.Conclusion: In this population-based inception cohort, the largest MNCD primary care drug utilization study conducted to date, MNCD drug utilization varied by sex, age and MNCD subtype.v ajusté : 1,11; IC à 95 % : 1,07 à 1,14), moins susceptibles d'arrêter le traitement avec le donépézil (RRI ajusté : 0,96; IC à 95 % : 0,93 à 0,99) et moins susceptibles d'être non observantes (RRI ajusté : 0.91, IC à 95 % : 0,87 à 0,96) au traitement avec le donépézil.Comparativement aux patients diagnostiqués entre 65 et 74 ans, les patients diagnostiqués après 95 ans avaient reçu plus fréquemment de la mémantine (28 % p/r à 9 %), étaient moins susceptibles de passer à un autre médicament (RRI ajusté : 0,25; IC à 95 % : 0,23 à 0,28), affichaient moins de persistance et présentaient un taux plus élevé de non-observance.Des différences ont été observées entre les 5 sous-types de démence quant à la prescription de médicaments pour les TNM, aux passages à d'autres médicaments et à la persistance, mais pas en ce qui a trait à l'observance.Conclusion : Dans cette cohorte populationnelle de patients suivis depuis le début de leur maladie, qui constitue la plus vaste étude sur l'usage de médicaments pour les TNM en soins primaires menée à ce jour, l'utilisation de ces médicaments variait en fonction du genre et de l'âge des patients, et du sous-type de TNM.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".