Time-related biases in pharmacoepidemiology.
Pharmacoepidemiol Drug Saf. 2020 Aug 11;:
Authors: Suissa S, Dell'Aniello S
PURPOSE: Observational studies using computerized healthcare databases have become popular to investigate the potential effectiveness of old drugs for new indications. Many of these studies reporting remarkable effectiveness were shown to be affected by different time-related biases. We describe these biases and illustrate their effects using a cohort of patients treated for chronic obstructive pulmonary disease (COPD).
METHODS: The Quebec healthcare databases were used to form a cohort of 124 030 patients with COPD, 50 years or older, treated between 2000 and 2015. Inhaled corticosteroids (ICS) and long-acting bronchodilators were used as exposures, with diverse outcomes, including lung cancer, acute myocardial infarction and death, to illustrate protopathic, latency time, immortal time, time-window, depletion of susceptibles, and immeasurable time biases.
RESULTS: Protopathic bias affected bronchodilator-defined cohort entry with an incident rate of lung cancer of 23.9 per 1000 in the first year, compared with around 12.0 in the subsequent years. When latency and immortal times were misclassified, ICS were associated with decreased incidence of lung cancer (hazard ratio [HR] 0.32; 95% CI: 0.30-0.34), compared with 0.50 (95% CI: 0.48-0.53) after correcting for immortal time bias and 0.96 (95% CI: 0.91-1.02) after also correcting for latency time bias. Time-window, depletion of susceptibles and immeasurable time biases also affected the findings similarly.
CONCLUSIONS: Many observational studies of new indications for older drugs reporting unrealistic effectiveness were affected by avoidable time-related biases. The apparent effectiveness often disappears with proper design and analysis. Future studies should consider these time-related issues to avoid severely biased results.
PMID: 32783283 [PubMed - as supplied by publisher]
Pneumonia Hospitalization Coding Changes Associated With Transition From the 9th to 10th Revision of International Classification of Diseases.
Health Serv Res Manag Epidemiol. 2020 Jan-Dec;7:2333392820939801
Authors: Smithee RB, Markus TM, Soda E, Grijalva CG, Xing W, Shang N, Griffin MR, Lessa FC
Objectives: To evaluate the impact of International Classification of Disease, 10th revision, Clinical Modification (ICD-10-CM) implementation on pneumonia hospitalizations rates, which had declined following pneumococcal conjugate vaccine introduction for infants in 2000.
Methods: We randomly selected records from a single hospital 1 year before (n = 500) and after (n = 500) October 2015 implementation of ICD-10-CM coding. We used a validated ICD-9-CM algorithm and translation of that algorithm to ICD-10-CM to identify pneumonia hospitalizations pre- and post-implementation, respectively. We recoded ICD-10-CM records to ICD-9-CM and vice versa. We calculated sensitivity and positive predictive value (PPV) of the ICD-10-CM algorithm using ICD-9-CM coding as the reference. We used sensitivity and PPV values to calculate an adjustment factor to apply to ICD-10 era rates to enable comparison with ICD-9-CM rates. We reviewed primary diagnoses of charts not meeting the pneumonia definition when recoded.
Results: Sensitivity and PPV of the ICD-10-CM algorithm were 94% and 92%, respectively, for young children and 74% and 79% for older adults. The estimated adjustment factor for ICD-10-CM period rates was -2.09% (95% credible region [CR], -7.71% to +3.0%) for children and +6.76% (95% CR, -3.06% to +16.7%) for older adults. We identified a change in coding adult charts that met the ICD-9-CM pneumonia definition that led to recoding in ICD-10-CM as chronic obstructive pulmonary disease (COPD) exacerbation.
Conclusions: The ICD-10-CM algorithm derived from a validated ICD-9-CM algorithm should not introduce substantial bias for evaluating pneumonia trends in children. However, changes in coding of pneumonia associated with COPD in adults warrant further study.
PMID: 32782916 [PubMed]
The Global Usability Score Short-Form for the simplified assessment of dry powder inhalers (DPIs) usability.
Multidiscip Respir Med. 2020 Jan 28;15(1):659
Authors: Povero M, Turco P, Bonadiman L, Dal Negro RW
Background: The choice of the Dry Powder Inhaler (DPI) to prescribe is a critical issue. The estimation of DPIs usability depends on the objective assessment of several indices related to both subjective and objective determinants. The Global Usability Score (GUS) Questionnaire is a comprehensive tool usable for checking, comparing, and ranking inhalers' usability objectively in real life, but it takes some time to fill.
Aim: The aim of this study was to favour the quicker check of DPIs usability in clinical practice by means of a simplified short-form GUS (S-GUS) Questionnaire, while maintaining the high specificity and sensitivity of the original, extended version of the Questionnaire (O-GUS questionnaire).
Methods: The usability of the six most prescribed DPIs was assessed in 222 patients with persistent airway obstruction and needing long-term inhalation treatments. LASSO regression and multicollinearity test were used to select the subset of questions of the O-GUS questionnaire, with the highest information power. Each item was then scored using the corresponding coefficient in the linear regression (normalized at 50 as the O-GUS score). Agreement between the original and the short-form questionnaire was evaluated using the Cohen's kappa statistic (κ). The overall S-GUS values obtained for each DPI were then compared to those from the O-GUS, in the same patients, using a Bayesian indirect comparison (IC) model.
Results: After the statistical selection of the items mostly contributing to the overall score, the novel S-GUS questionnaire consists of twelve items only. Nine items are related to patients' opinion before DPIs handling, and three to the nurse's assessment after DPIs practicality. O-GUS and S-GUS score were strongly correlated (R2=0.9843, p<0.0001) and the usability score calculated for each DPI by means of the O- and of S- GUS overlapped almost completely (κ=84.5%, 95% CI 81.3% to 89.2%). Furthermore, S-GUS was much faster to complete than O-GUS (mean time 6.1 vs 23.4 minutes, p<0.001). Estimates of S-GUS, obtained from the IC model, allowed to propose a simple classification of usability: "good" by GUS values >25; "pretty good" by values ≤25≥15, and "insufficient" by values <15.
Conclusions: The S-GUS proves as much specific and suitable as the extended O-GUS questionnaire in measuring DPIs usability, while maintaining the same high sensitivity. As the time required for its use is quite shorter, S-GUS is also particularly suitable and helpful in current clinical practice.
PMID: 32782791 [PubMed]
Differential lung inflammation and injury with tobacco smoke exposure in Wistar Kyoto and spontaneously hypertensive rats.
Inhal Toxicol. 2020 Aug 11;:1-14
Authors: Pham AK, Wu CW, Qiu X, Xu J, Smiley-Jewell S, Uyeminami D, Upadhyay P, Zhao D, Pinkerton KE
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and has been associated with periods of intense lung inflammation. The objective of this study was to characterize whether similar rat strains, possessing different genetic predispositions, might play a role in exacerbating the pathophysiology of COPD-like cellular and structural changes with progressive 12-week exposure to tobacco smoke (TS). Normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats were compared.
MATERIALS AND METHODS: WKY and SH rats were exposed to filtered air or to tobacco smoke at a particulate concentration of 80 mg/m3 for 4, 8, or 12 weeks. Necropsy was performed 24 h after the last exposure to obtain cells by bronchoalveolar lavage for total cell and differential counts. Scoring of lung tissues and immunohistochemical staining for M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages were performed on paraffin-embedded lung sections.
RESULTS AND DISCUSSION: With progressive exposure, TS-exposed SH rats demonstrated significant airspace enlargement, mucin production, and lung inflammation compared to their FA control and TS-matched WKY rats. Moreover, SH rats also demonstrated increased expression of the M1 marker in alveolar macrophages compared to FA control, as well as the M2 marker compared to controls and TS-exposed WKY rats.
CONCLUSION: The progressive tobacco smoke exposure contributes to persistent lung injury and inflammation that can be significantly enhanced by rat strain susceptibility in the genesis of COPD.
PMID: 32781858 [PubMed - as supplied by publisher]
Prevalence and Characteristics of Undiagnosed COPD in Adults 40 Years and Older - Reports from the Tunisian Population-Based Burden of Obstructive Lung Disease Study.
COPD. 2020 Aug 12;:1-8
Authors: Denguezli M, Daldoul H, Harrabi I, Chouikha F, Ghali H, Burney P, Tabka Z
This study aimed to investigate the underdiagnosis of COPD and its determinants based on the Tunisian Burden of Obstructive Lung Disease study. We collected information on respiratory history symptoms and risk factors for COPD. Post-bronchodilator (Post-BD) FEV1/FVC < the lower limit of normal (LLN) was used to define COPD. Undiagnosed COPD was considered when participants had post-BD FEV1/FVC < LLN but were not given a diagnosis of emphysema, chronic bronchitis or COPD. 730 adults aged ⩾40 years selected from the general population were interviewed, 661 completed spirometry, 35 (5.3%) had COPD and 28 (80%) were undiagnosed with the highest prevalence in women (100%). When compared with patients with an established COPD diagnosis, undiagnosed subjects had a lower education level, milder airway obstruction (Post-BD FEV1 z-score -2.2 vs. -3.7, p < 0.001), fewer occurrence of wheezing (42.9% vs. 100%, p = 0.009), less previous lung function test (3.6% vs. 42.8%, p = 0.019) and less visits to the physician (32.1% vs. 85.7%, p = 0.020) in the past year. Multivaried analysis showed that the probability of COPD underdiagnosis was higher in subjects who had mild to moderate COPD and in those who did not visit a clinician and did not perform a spirometry in the last year. Collectively, our results highlight the need to improve the diagnosis of COPD in Tunisia. Wider use of spirometry should reduce the incidence of undiagnosed COPD. Spirometry should also predominately be performed not only in elderly male smokers but also in younger women in whom the prevalence of underdiagnosis is the highest.
PMID: 32781855 [PubMed - as supplied by publisher]