Pragmatic and Observational Research最新文献

Background: Healthcare systems are under increasing strain, predominantly due to chronic non-communicable diseases. Connected healthcare technologies are becoming ever more capable and their components cheaper. These innovations could facilitate both self-management and more efficient use of healthcare resources for common respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, newer technologies can only facilitate major changes in practice, and cannot accomplish them in isolation.

Focus of review: There are now large numbers of devices and software offerings available. However, the potential of such technologies is not being realised due to limited engagement with the public, clinicians and providers, and a relative paucity of evidence describing elements of best practice in this complex and evolving environment. Indeed, there are clear examples of wasted resources and potential harm. We therefore call on interested parties to work collaboratively to begin to realize the potential benefits and reduce the risks of connected technologies through change in practice. We highlight key areas where such partnership can facilitate the effective and safe use of technology in chronic respiratory care: developing data standards and fostering inter-operability, making collaborative testing facilities available at scale for small to medium enterprises, developing and promoting new adaptive trial designs, developing robust health economic models, agreeing expedited approval pathways, and detailed planning of dissemination to use.

Conclusion: The increasing capability and availability of connected technologies in respiratory care offers great opportunities and significant risks. A co-ordinated collaborative approach is needed to realize these benefits at scale. Using newer technologies to revolutionize practice relies on widespread engagement and cannot be delivered by a minority of interested specialists. Failure to engage risks a costly and inefficient chapter in respiratory care.

Background: We sought to determine from key clinical outcomes whether catheter ablation of atrial fibrillation (AF) is associated with increased survival.

Methods and results: Using routinely collected hospital data, ablation patients were matched to two control cohorts using direct and propensity score methodology. Four thousand nine hundred ninety-one ablation patients were matched 1:1 with general AF controls without ablation. Five thousand four hundred seven ablation patients were similarly matched to controls who underwent cardioversion. We examined the rates of ischemic stroke or transient ischemic attack (stroke/TIA), heart failure hospitalization, and death. Matched populations had very similar comorbidity profiles, including nearly identical CHA₂DS₂-VASc risk distribution (p=0.6948 and p=0.8152 vs general AF and cardioversion cohorts). Kaplan-Meier models showed increased survival after ablation for all outcomes compared with both control cohorts (p<0.0001 for all outcomes vs general AF, p=0.0087 for stroke/TIA, p<0.0001 for heart failure, and p<0.0001 for death vs cardioversion). Cox regression models also showed improved survival after ablation for all outcomes compared with the general AF cohort (hazard ratio [HR]=0.4, 95% confidence interval [95% CI]: 0.3-0.6, p<0.0001 for stroke/TIA; HR=0.4, 95% CI: 0.2-0.6, p<0.0001 for heart failure; HR=0.1, 95% CI: 0.1-0.1, p<0.0001 for death) and the cardioversion cohort (HR=0.6, 95% CI: 0.4-0.9, p=0.0111 for stroke/TIA; HR=0.4, 95% CI: 0.3-0.6, p<0.0001 for heart failure; HR=0.3, 95% CI:0.2-0.5, p<0.0001 for death).

Conclusions: Catheter ablation of AF was associated with very significant reductions in mortality, stroke/TIA, and heart failure compared with a matched general AF population and a matched population who underwent cardioversion. Potential confounding of outcomes was minimized by very tight cohort matching.

Background: We sought to determine whether catheter ablation of atrial fibrillation (AF) is associated with reduced occurrence of ischemic cerebrovascular events.

Methods and results: Using routinely collected hospital data, ablation patients were matched to two control cohorts via direct and propensity score matching. A total of 4,991 ablation patients were matched 1:1 to general AF controls with no ablation, and 5,407 ablation patients were similarly matched to controls who underwent cardioversion. Yearly rates of ischemic stroke or transient ischemic attack (stroke/TIA) before and after an index date were compared between cohorts. Index date was defined as the first ablation, the first cardioversion, or the second AF event in the general AF cohort. Matched populations had very similar demographic and comorbidity profiles, including nearly identical CHA₂DS₂-VASc risk distribution (p-values 0.6948 and 0.8152 vs general AF and cardioversion cohorts). Statistical models of stroke/TIA risk in the preindex period showed no difference in annual event rates between cohorts (mean±standard error 0.30% ± 0.08% ablation vs 0.28% ± 0.07% general AF, p=0.8292; 0.37% ± 0.09% ablation vs 0.42% ± 0.08% cardioversion, p=0.5198). Postindex models showed significantly lower annual rates of stroke/TIA in ablation patients compared with each control group over 5 years (0.64% ± 0.11% ablation vs 1.84% ± 0.23% general AF, p<0.0001; 0.82% ± 0.15% ablation vs 1.37% ± 0.18% cardioversion, p=0.0222).

Conclusion: Matching resulted in cohorts having the same baseline risks and rates of ischemic cerebrovascular events. After the index date, there were significantly lower yearly event rates in the ablation cohort. These results suggest the divergence in outcome rates stems from variance in the treatment pathways beginning at the index date.

The source and significance of residual low-level viremia (LLV) during combinational antiretroviral therapy (cART) remain a matter of controversy. It is unclear whether residual viremia depends on ongoing release of HIV from the latent reservoir or if viral replication contributes to LLV. We examined the relationship between adherence and LLV. Adherence was estimated by pharmacy refill and dichotomized as ≥95% or <95%. Plasma HIV-RNA was determined, with an ultrasensitive test having a limit of detection of 3 copies/mL at least 2 times over the follow-up period. Patients were grouped according to HIV-RNA over time as K<3: constantly <3 copies/mL; V<3: sometimes below or above the cutoff limit but always <50 copies/mL; K>3: constantly between 3 and 50 copies/mL; and V>50: a measure of >50 copies/mL minimum. Overall, 2789 patients were included. At each time point approximately 92% of the patients presented an HIV-RNA <50 copies/mL and two-thirds of those <3 copies/mL, 34.6% of patients had <3 copies/mL constantly, 32.7% sometimes below or above the cutoff limit but always <50 copies/mL, 9.5% constantly between 3 and 50 copies/mL, and 23.2% a measure of >50 copies/mL minimum. The mean adherence rate was 92.1% (95% confidence interval [CI] from 91.1% to 93.1%) in K<3 patients, similar in V<3 patients (91.9%), but lowered to 88.8% in K>3 patients and to 88.4% in V>50 patients (P<0.0001). Approximately 55% of patients in groups K<3 and V<3 showed an adherence rate ≥95%; this proportion lowered to ~51% in K>3 and to 48% in V>50. Moreover, 34% of patients with a steady adherence <95% were categorized as K>3, whereas 21.7% of those with a drug holiday (21.7%) were observed in the V>50 group (P=0.002). A steady viral suppression can occur despite moderate cART non-adherence, but reduced adherence is associated with low-level residual viremia, which could reflect new rounds of HIV replication. However, a detectable HIV-RNA could also be detected in patients with optimal cART adherence, indicating additional mechanisms favoring HIV persistence.

Background: Acute heart failure (AHF) is a common presentation in the Emergency Department (ED), and most patients are admitted to the hospital. Identification of patients with AHF who have a low risk of adverse events and are suitable for discharge from the ED is difficult, and an objective tool would be useful.

Methods: The highly sensitive Troponin T Rules Out Acute Cardiac Insufficiency Trial (TACIT) will enroll ED patients being treated for AHF. Patients will undergo standard ED evaluation and treatment. High-sensitivity troponin T (hsTnT) will be drawn at the time of enrollment and 3 hours after the initial draw. The initial hsTnT draw will be no more than 3 hours after initiation of therapy for AHF (vasodilator, loop diuretic, noninvasive ventilation). Treating clinicians will be blinded to hsTnT results. We will assess whether hsTnT, as a single measurement or in series, can accurately predict patients at low risk of short-term adverse events.

Conclusion: TACIT will explore the value of hsTnT measurements in isolation, or in combination with other markers of disease severity, for the identification of ED patients with AHF who are at low risk of short-term adverse events.

Objective: The objective of this study was to determine whether the effectiveness of budesonide comparator is non-inferior to budesonide reference in the prevention of asthma exacerbations. Asthma-related hospitalizations and safety were also examined.

Methods: This study used a matched, historic cohort design. Data were drawn from the Clinformatics™ Data Mart US claims database and included a 1-year baseline, starting 1 year before the index prescription date, and a 1-year outcome period. Patients received budesonide comparator or reference treatment. The primary outcome was the rate of asthma exacerbations. Non-inferiority for budesonide comparator vs budesonide reference was established if the 95% confidence interval (CI) upper limit of mean difference in proportions between treatments was <15%. Secondary outcomes examined rate of asthma-related hospitalizations and adverse events (AEs).

Results: The budesonide comparator and reference-matched cohorts each included 3109 patients. The adjusted upper 95% CI for the difference in proportions of patients experiencing asthma exacerbations was 0.035 (3.5%), demonstrating non-inferiority. Cohorts did not significantly differ in the rate of asthma exacerbations (adjusted rate ratio [RR]=1.04, 95% CI: 0.95-1.14) or rate of asthma-related hospitalizations (adjusted RR=1.10, 95% CI: 0.99-1.24) after adjusting for baseline confounders. No asthma exacerbations occurred during the outcome period in 72.9% of budesonide comparator patients and 71.8% of budesonide reference patients. No asthma-related hospitalizations occurred in 77.9% of patients in the budesonide comparator cohort and 79.0% of patients in the budesonide reference cohort. The most frequent AEs were throat irritation (≤0.4% of patients) and hoarseness/dysphonia (0.02% of patients). AEs did not significantly differ between treatment cohorts.

Conclusion: In this real-life study, non-inferiority of the budesonide comparator vs reference was met for the primary end point of asthma exacerbation rates. Asthma-related hospitalization and AE rates did not differ between the two treatment cohorts. The budesonide comparator is an effective and safe treatment alternative for asthma exacerbations.

Background: Differentiated thyroid cancer (DTC) occurs in relatively young patients and is associated with a good prognosis and long survival. The management of this disease involves thyroidectomy, radioiodine therapy, and long-term thyroid-stimulating hormone suppression therapy (THST). The long-term effects of the treatment and the interaction between subclinical hyperthyroidism and long-term hypoparathyroidism are poorly understood. This review sought to examine the available evidence.

Methods: A PubMed search was carried out using the search terms "Thyroid Neoplasms" AND ("Thyroxine" OR "Hypocalcemia" OR "Thyrotropin"). Original English language articles published in the last 30 years studying the morbidity from thyroid-stimulating hormone (TSH) suppression and hypoparathyroidism following a surgery for DTC were retrieved and reviewed by 2 authors.

Results: Of the 3,000 results, 66 papers including 4,517 patients were selected for the present study. Studies reported on a range of skeletal (included in 34 studies, 1,647 patients), cardiovascular (17 studies, 957 patients), psychological (10 studies, 663 patients), and other outcomes (10 studies, 1,348 patients). Nine of 26 studies on patients who underwent THST showed a reduction in bone density, and 13 of 23 studies showed an increase in bone turnover markers. Skeletal effects were more marked in postmenopausal women. There was no evidence of increased fracture risk, and only little data were available on hypoparathyroidism. Four of five studies showed an increased left ventricular mass index on echocardiography, and one study showed a higher prevalence of atrial fibrillation (AF). There was little difference in basic physiological parameters and limited literature regarding symptoms or significant events. Six studies showed associations between long-term TSH suppression and impaired quality of life. Impaired glucose metabolism and prothrombotic states were also found in DTC patients.

Conclusion: There is limited literature regarding long-term DTC treatment-related morbidity, particularly regarding the effects of long-term hypocalcemia. Most studies have focused on surrogate markers and not on clinical outcomes. A large prospective study on defined clinical outcomes would help characterize the morbidity of treatment and stimulate research on tailoring treatment strategies.

Evidence-based practice is an important component of health care service delivery. However, there is a tendency, embodied in tools such as Grades of Recommendation, Assessment, Development, and Evaluation, to focus principally on the classification of study design, at the expense of a detailed assessment of the strengths and limitations of the individual study. Randomized controlled trials (RCTs), and in particular the classical "explanatory" RCT, have a privileged place in the hierarchy of evidence. However, classical RCTs have substantial limitations, most notably a lack of generalizability, which limit their direct applicability to clinical practice implementation. Pragmatic and observational studies can provide an invaluable perspective into real-world applicability. This evidence could be used more widely to complement ideal-condition results from classical RCTs, following the principle of triangulation. In this review article, we discuss several types of pragmatic and observational studies that could be used in this capacity. We discuss their particular strengths and how their limitations may be overcome and provide real-life examples by means of illustration.

Background: Motor vehicle collisions (MVCs) are a leading cause of injury in the US. While the probability of collision with a pedestrian (PMVC) has declined in recent years, the probability of a pedestrian fatality has risen. Our objective was to determine whether older age impacts potential outcomes in patients involved in low-velocity PMVCs.

Materials and methods: We performed a retrospective-cohort study of adult patients aged >14 years involved in low-velocity pedestrian-MVCs (<15 miles per hour [24.14 km/h]), presenting to an urban level I trauma center from January to November 2013. Subjects were identified via trauma registry and stratified: ages 15-49 years and ≥50 years. Electronic medical records were reviewed for demographics, vital signs, and laboratory results on initial presentation, presence or absence of systemic inflammatory response syndrome (SIRS), shock index (SI), injury-severity score (ISS), length of stay (LOS), and survival to discharge. For statistical analysis, χ² or Student's t-tests were utilized.

Results: Our study included 145 patients (77 female) with a mean age of 41.9±3 years; 95 patients were aged 15-49 years (mean 31.9±2.2 years), and 50 patients were aged ≥50 years or older (mean 62.44±2.9 years). Mean ISS was 10.05±1.95, mean SI was 0.68±0.03, and mean LOS was 3.67±0.57 days. A total of 41 patients met SIRS criteria on arrival, and nine patients expired (6.2%). Mean ISS (15.64±4.42 vs 7.1±1.64, P<0.001) and mean SI (0.75±0.07 vs 0.65±0.03, P=0.002) were higher in patients aged ≥50 years. Mean LOS was longer in older patients (5.22±1.14 vs 2.85±0.58 days, P<0.001). Older age was associated with SIRS on arrival (P=0.023) and associated with mortality (P=0.004).

Conclusion: Age ≥50 years is associated with greater severity of injury and poor outcomes for patients involved in low-velocity PMVCs. Increased clinical attention and resource allocation should be directed toward older patients after low-velocity PMVCs.

Background: Adherence to asthma and chronic obstructive pulmonary disease (COPD) treatment has been shown to depend on patient-level factors, such as disease severity, and medication-level factors, such as complexity. However, little is known about the impact of prescription charges - a factor at the health care system level. This study used real-life data to investigate whether co-payment affects adherence (implementation and persistence) and disease outcomes in patients with asthma or COPD.

Methods: A matched, historical cohort study was carried out using two UK primary care databases. The exposure was co-payment for prescriptions, which is required for most patients in England but not in Scotland. Two comparison cohorts were formed: one comprising patients registered at general practices in England and the other comprising patients registered in Scotland. Patients aged 20-59 years with asthma, or 40-59 years with COPD, who were initiated on fluticasone propionate/salmeterol xinafoate, were included, matched to patients in the opposite cohort, and followed up for 1 year following fluticasone propionate/salmeterol xinafoate initiation. The primary outcome was good adherence, defined as medication possession ratio ≥80%, and was analyzed using conditional logistic regression. Secondary outcomes included exacerbation rate.

Results: There were 1,640 patients in the payment cohort, ie, England (1,378 patients with asthma and 262 patients with COPD) and 619 patients in the no-payment cohort, ie, Scotland (512 patients with asthma and 107 patients with COPD). The proportion of patients with good adherence was 34.3% and 34.9% in the payment and no-payment cohorts, respectively, across both disease groups. In a multivariable model, no difference in odds of good adherence was found between the cohorts (odds ratio, 1.04; 95% confidence interval, 0.85-1.27). There was also no difference in exacerbation rate.

Conclusion: There was no difference in adherence between matched patients registered in England and Scotland, suggesting that prescription charges do not have an impact on adherence to treatment.