Change In Guideline Recommendations Research Articles

Online searches for hepatocellular carcinoma drugs mirror prescription trends across specialties and changes in guideline recommendations.

The treatment options for systemically progressed hepatocellular carcinoma (HCC) have significantly expanded in recent years. In this study, we aimed to evaluate the potential of Google searches as a reflection of prescription rates for HCC drugs in the United States (US). We conducted an in-depth analysis of US prescription data obtained from the IQVIA National Prescription Audit (NPA) and corresponding Google Trends data from January 2017 to December 2022. We focused on drugs used in the first line and second or later treatment lines for HCC, collecting data on their prescriptions and search rates. Search volumes were collected as aggregated search queries for both generic drugs and their respective brand names. During the study period from Q1 2017 to Q4 2022, monthly prescriptions for drugs used in HCC treatment showed an 173% increase (from 1253 to 3422). Conversely online searches increased by 3.5% (from 173 to 179 per 10 million searches). Notably, strong correlations were observed between search interest and prescriptions for newer drugs, which indicates increasing usage, while older drugs with declining usage displayed limited correlation. Our findings suggest a growing role of non-physician professions in managing systemically progressed HCC within the US healthcare system, although oncologists remained primarily responsible for drug prescriptions. In conclusion, online search monitoring can offer the potential to reflect prescription trends specifically related to the treatment of HCC. This approach provides a swift and accessible means of evaluating the evolving landscape of HCC treatment.

Current practice of intracranial pressure monitoring in children with severe traumatic brain injury-a nationwide prospective surveillance study in Germany.

For management of severe traumatic brain injuries (sTBI) in children, the overall level of evidence to guide diagnostic and therapeutic procedures is low. Since 2016, international guidelines have subsequently suggested invasive intracranial pressure (ICP) monitoring in patients with initial Glasgow Coma Scale (GCS) ≤8. In Germany, ICP monitoring was an individual case decision from 2011 until the 2022 update of the German pediatric TBI guideline. The aim of this study was to evaluate current clinical practice of invasive ICP monitoring in Germany in children <10 years with respect to guideline recommendations. Anonymized clinical data on sTBI cases <10 years of age were collected in a nationwide prospective surveillance study via the German Pediatric Surveillance Unit ESPED from July 2019 until June 2022. Inclusion criteria for the surveillance study were sTBI (initial GCS ≤8) or neurosurgery following TBI. For this analysis, only cases with GCS ≤8 were subject to the present analysis. Descriptive analyses were performed to assess the proportion of ICP monitored patients and describe the cohort. Out of 217 reported cases, 102 cases met the inclusion criteria and thus qualified for ICP monitoring. Of these, 37 (36%) received ICP monitoring. Monitored patients were older, had lower median GCS values at presentation (4 vs. 5), higher mortality (32% vs. 22%), and were more frequently diagnosed with cerebral edema (68% vs. 37%). In children <10 years with sTBI, the present clinical management regarding ICP monitoring deviates from the current German national and international guidelines. The reasons remain unclear, with the low level of evidence in the field of ICP monitoring and the recency of changes in guideline recommendations as potential contributors. Prospective interventional studies should elucidate the benefit of ICP monitoring and ICP directed therapies to provide evidence-based recommendations on ICP monitoring.

Diagnostic Imaging in the Evaluation of Asymptomatic Microhematuria: Systematic Review and Meta-analysis.

Microhematuria is a highly prevalent condition with a low associated risk of urothelial and upper tract malignancy. The AUA Guidelines recently changed recommendations for imaging favoring renal ultrasound for low and intermediate risk patients with microhematuria. We summarize the diagnostic test characteristics of computed tomography urography, renal ultrasound, and magnetic resonance urography in comparison with surgical pathology for the diagnosis of upper urinary tract cancer in microhematuria and gross hematuria patients. This study is a systematic review and meta-analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from evidence collected for the 2020 AUA Microhematuria Guidelines report, including studies assessing imaging following diagnosis of hematuria published from January 2010 through December 2019. The search identified 20 studies which reported the prevalence of malignant and benign diagnoses in relation to imaging modality, of which 6 were included in the quantitative analysis. For the detection of renal cell carcinoma and upper urinary tract carcinoma in patients with microhematuria and gross hematuria, computed tomography urography had a sensitivity of 94% (95% CI, 84%-98%) and a specificity of 99% (95%CI, 97%-100%) with a certainty of evidence rating of very low and low, respectively when 4 studies were pooled. In comparison, ultrasound demonstrated a sensitivity ranging from 14%-96% (low certainty of evidence) and a specificity of 99%-100% in 2 studies (moderate certainty of evidence), while magnetic resonance urography demonstrated a sensitivity of 83% and specificity of 86% in 1 study with a low certainty of evidence. In a limited data set for each individual imaging modality, computed tomography urography appears the most sensitive imaging modality for the diagnostic evaluation of microhematuria. Future studies will be needed to evaluate the clinical and health system financial impacts of the change in guideline recommendations from computed tomography urography to renal ultrasound in evaluating low and intermediate risk patients with microhematuria.

Temporal changes of patient characteristics over 12 years in a single-center transcatheter aortic valve implantation cohort

BackgroundBeneficial results of transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) in patients at all risk strata have led to substantial changes in guideline recommendations for valvular heart disease.AimTo examine influence of these guideline changes on a real-world TAVI cohort, we evaluated how risk profiles and outcomes of TAVI patients developed in our single-center patient cohort over a period of 12 years.MethodsBaseline, procedural and 30-day outcome parameters of TAVI patients were retrospectively compared between three time periods (period 1: 2008–2012, period 2: 2013–2017, period 3: 2018–2020).ResultsBetween 03/2008 and 12/2020, a total of 3678 patients underwent TAVI at our center. The median age was 81.1 years (25th, 75th percentile: 76.7, 84.9) with no significant change over time. The EuroSCORE II showed a continuous and significant decline from 5.3% (3.3, 8.6) in period 1 to 2.8% (1.7, 5.0) in period 3 (p < 0.001). Furthermore, rates of permanent pacemaker implantation, acute kidney injury, and paravalvular leakage ≥ moderate continuously declined over time. Accordingly, the 30-day mortality fell from 9.3% in period 1 to 4.3% in period 3 (p < 0.001).ConclusionDespite substantial guideline alterations, median patient age remained largely unchanged in our TAVI cohort over the past 12 years. Therefore, increased age still appears to be the main reason to choose TAVI over SAVR. However, risk profiles declined substantially. Significant improvements in early outcomes suggest favorable influence of less invasive access routes, improved device platforms and growing user experience.Graphical abstract

Current treatment status of patients with idiopathic pulmonary fibrosis in Japan based on a claims database analysis

Treatment for idiopathic pulmonary fibrosis (IPF) has changed over the past decades. Understanding the actual status of IPF treatment and evaluating the consistency of the guidelines are important for improving the treatment strategy. However, the relevant information is insufficient in Japan. Therefore, this study investigated the treatment status and changes in the treatment of patients with IPF in Japan. This retrospective claims-based study used a Japanese claims database that included data from acute care hospitals (April 2008-March 2019). Patients with at least one record of definitive IPF diagnosis were classified as patients with IPF. We determined the percentage of patients who received each treatment type by the year. We analyzed 9961 patients with IPF. The mean (standard deviation) age at first diagnosis was 74.4 (9.3) years, and 74.9% of the patients were men. The number of patients who did not take any drug treatment tended to decrease over the years. Nevertheless, approximately 30% of the patients did not take any drug treatment in recent years. The number of patients who received antifibrotic drugs increased over time, and it became the most popular treatment for ≥40% of the patients in and after 2017. Although steroid prescriptions tended to decrease over time, they were still administered to one-third of the patients with IPF who received drug treatment in and after 2017. Our findings suggest that changes in the IPF treatment reflect changes in guideline recommendations as well as the availability of treatment in clinical settings in Japan.

Temporal changes in anticoagulant prescribing and atrial fibrillation: results of interrupted time-series analysis of openly available routine data in England

Abstract Introduction The use of anticoagulants for stroke prevention in patients with atrial fibrillation (AF) has been increasing in England in the recent years (1, 2). The changes in practice coincided with several developments in the area of anticoagulants and AF, including: the emergence of evidence supporting anticoagulant use for stroke prevention in AF, changes in guideline recommendations, and the licensing of direct oral anticoagulants (DOACs) as an alternative to warfarin, which was the mainstay of stroke prevention in AF. Currently, there are four DOACs available for use: dabigatran, rivaroxaban, apixaban, and edoxaban. Recent analyses of time trends of anticoagulant prescribing in England showed an increase in DOACs prescribing and a decrease in warfarin prescribing (1, 2). However, more recent exploration of recent anticoagulant prescribing trends is needed. Aim To explore the changes in anticoagulant prescribing for AF in England. Methods Interrupted time-series analysis (ITSA) of openly available data on anticoagulant prescribing and AF. Separate analyses were conducted for data from Sentinel Stroke National Audit Programme (SSNAP) and Quality and Outcomes Framework (QOF). The timeframe of the analysis and the length of time intervals depended on the characteristics of each dataset. Results Analysis of data from SSNAP showed that the proportion of stroke patients who have a diagnosis of AF who were taking an anticoagulant alone prior to admission increased from 32.51% in the third quarter of 2013 to 62.63% in the third quarter of 2020; this coincided with a decreased proportion of stroke patients who have a diagnosis of AF taking antiplatelets alone from 37.10% to 8.31% during the same period. Analysed QOF data on anticoagulants and AF included information about AF prevalence in QOF datasets, the eligibility of patients with AF for anticoagulant based on stroke risk assessment, and the use of anticoagulants among eligible patients. Prevalence of AF in England in QOF datasets increased from 1.52% in 2012/2013 to 2.05% in 2019/2020 (ITSA gradient=0.08, p-value&amp;lt;.001, 95% confidence interval: 0.07- 0.09). The proportion of patients with AF who are considered eligible for anticoagulation per all patients with AF in QOF datasets increased from 44.95% in 2012/2013 to 80.87% in 2019/2020; there was an increase by 25.24% between 2014/2015 and 2015/2016 which corresponds to modifying risk assessment scores to include additional criteria. The proportion of eligible patients with AF being prescribed anticoagulants also increased in the period between 2012/2013 and 2019/2020 (ITSA gradient = 1.98, p-value&amp;lt;.001, 95% confidence interval: 1.52- 2.44). Conclusion The analysis of data from different sources identified an increase in anticoagulant prescribing for patients with AF in England, which is likely to translate into health gains. However, the use of aggregate data in the analysis did not allow for detailed inspection of patient characteristics, and individual anticoagulants were not specified in the datasets. Therefore, quantitative analyses of primary care data of individual anticoagulant prescribing for different patient groups with AF are needed to further understand whether additional improvements are possible in the prevention of complications from atrial fibrillation. References (1) Adderley NJ, Ryan R, Nirantharakumar K, Marshall T. Prevalence and treatment of atrial fibrillation in UK general practice from 2000 to 2016. Heart. 2019;105(1):27-33. (2) Loo SY, Dell’Aniello S, Huiart L, Renoux C. Trends in the prescription of novel oral anticoagulants in UK primary care. British Journal of Clinical Pharmacology. 2017;83(9):2096-106.

1107-P: Trends of First-Line Antidiabetic Treatment among 2007-2017 Medicare Beneficiaries Newly Diagnosed with Type 2 Diabetes (T2D) and Their Determinants

Background: Guidelines recommend initiating metformin at the time of T2D diagnosis in the absence of contraindications for asymptomatic patients. However, the evidence is scarce regarding real-world patterns and factors associated with antidiabetic treatment initiation in patients with newly diagnosed T2D. Methods: We used a 5% random sample of Medicare beneficiaries newly diagnosed with T2D in 2007-2017 and followed them for one year. The outcome was time to initiation of an antidiabetic agent within the first year of diagnosis. We examined trends in the proportion of outcome and the therapeutic class initiated by year. We constructed Cox Proportional Hazard models to identify factors associated with treatment initiation. Results: Of 231,408 patients newly diagnosed with T2D, the mean age was 71.7, and 62.2% were female. Only 13.7% initiated an antidiabetic agent within the first year of diagnosis. Although the proportion of initiation within one year of T2D diagnosis was relatively constant over time (12.7% in 2007 to 15.4% in 2017), the mean time to initiation decreased from 74.1 days in 2007 to 21.7 days in 2017 (p&amp;lt;0.05). Of those who initiated treatment, 54.2% and 21.5% initiated metformin and sulfonylurea in 2007, while 84.4% and 6.0% initiated metformin and sulfonylurea in 2017, respectively. In the adjusted model, age (HR 0.92, 95%CI 0.91-0.93 for 10-year increase), female sex (HR 0.89, 95%CI 0.87-0.91), number of comorbidities (HR 0.86, 95%CI 0.86-0.87 for one additional) and residence in urban areas (HR 0.78, 95%CI 0.76-0.80) were associated with decreased hazards of antidiabetic initiation. Conclusion: We found unexpectedly low rates of initiation of first-line treatment among Medicare beneficiaries with newly diagnosed T2D. The changes in the proportion of different drug classes reflect the change in guideline recommendations. Further investigation is needed to understand the causes underlying the low initiation. Disclosure Y. Li: None. I. Hernandez: Consultant; Self; Bristol-Myers Squibb Company, Pfizer Inc. N. Gabriel: None. S. L. Kane-gill: None. U. Essien: None. F. Toledo: Consultant; Self; AstraZeneca. J. Guo: None.

Macroscopic Fat in Adrenocortical Carcinoma: A Systematic Review.

OBJECTIVE. The objective of this systematic review was to determine the number and quality of reports of adrenocortical carcinoma (ACC) containing macroscopic fat; this information may inform guidelines for diagnosis and management of ACC. MATERIALS AND METHODS. A comprehensive search of databases of published studies was performed. Two reviewers independently selected original research, case series, or case reports of ACC with macroscopic fat on imaging and extracted data. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS. Three case reports and one retrospective study comprising a total of seven cases of ACC (lesion size: range, 6.5-22 cm) with macroscopic fat were included. ACC was symptomatic in all patients; neither locally invasive features nor metastases were reported. Four cases had less than 5% macroscopic fat on imaging, and the percentage fat on imaging was not reported for the remaining three cases. With regard to the risk of bias, one case had high risk for the index test domain because of potentially unreliable determination of macroscopic fat (i.e., no pathologic confirmation). All seven cases (from four studies) had unclear risk for the reference standard domain because there was insufficient information about the reference standard to determine whether ACC was correctly diagnosed. All studies were at low risk of bias in the flow and timing domain. CONCLUSION. There are few reports of macroscopic fat in ACC detected on imaging studies; among the reports of macroscopic fat in ACC, tumors were large (> 6 cm) and had a small proportion of gross fat (< 5%). The reliability of reported cases is questionable primarily because of insufficient details about pathologic diagnosis. Based on this information, a change in guideline recommendations may not be warranted. However, consideration of follow-up or biopsy of patients with large symptomatic tumors (> 6 cm) containing a small proportion of fat (< 5%) may be appropriate.

Pharmacokinetics and Safety of the Integrase Inhibitors Elvitegravir and Dolutegravir in Pregnant Women With HIV.

Objective: To synthesize data on the pharmacokinetics and safety of dolutegravir and elvitegravir in pregnant women living with HIV. Data Sources: A PubMed, EMBASE, Web of Science, and Google Scholar literature search (January 2010 to December 2018) was performed using the search terms dolutegravir, elvitegravir, women, pregnant*, and HIV. Additional reports were identified from conference abstracts and review of reference lists. Study Selection and Data Extraction: English-language studies reporting pharmacokinetic and/or safety data in pregnant women receiving dolutegravir or elvitegravir/cobicistat were included. Data Synthesis: A total of 17 studies were selected. Studies demonstrated a modest decrease in dolutegravir concentrations in pregnancy. Preliminary data suggest an increased risk of neural tube defects when dolutegravir is used at the time of conception. Available pharmacokinetic data in pregnant women showed significantly reduced plasma concentrations of elvitegravir/cobicistat which may increase the risk of virological failure. Current guidelines recommend that dolutegravir should not be initiated in women who have the potential to become pregnant or women in their first trimester of pregnancy and elvitegravir/cobicistat should be avoided during pregnancy. Relevance to Patient Care and Clinical Practice: This review highlights pharmacokinetic and safety data for dolutegravir and elvitegravir/cobicistat in pregnant women. Clinicians need to be aware of these data to convey the risks and benefits of using these agents in women of child-bearing potential. Conclusions: Changes in guideline recommendations reflect emerging data regarding the use of dolutegravir and elvitegravir/cobicistat in pregnancy. Until further information is available, raltegravir or other first-line agents are recommended for women with HIV planning to become pregnant.

Trends in advanced imaging and hospitalization for emergency department syncope care before and after ACEP clinical policy

ObjectivesTo describe recent trends in advanced imaging and hospitalization of emergency department (ED) syncope patients, both considered “low-value”, and examine trend changes before and after the publication of American College Emergency Physician (ACEP) syncope guidelines in 2007, compared to conditions that had no changes in guideline recommendations. MethodsWe analyzed 2002–2015 National Hospital Ambulatory Medical Care Survey data using an interrupted-time series with comparison series design. The primary outcomes were advanced imaging among ED visits with principal diagnosis of syncope and headache and hospitalization for ED visits with principal diagnosis of syncope, chest pain, dysrhythmia, and pneumonia. We adjusted annual imaging and hospitalization rates using survey-weighted multivariable logistic regression, controlling for demographic and visit characteristics. Using adjusted outcomes as datapoints, we compared linear trends and trend changes of annual imaging and hospitalization rates before and after 2007 with aggregate-level multivariable linear regression. ResultsFrom 2002 to 2007, advanced imaging rates for syncope increased from 27.2% to 42.1% but had no significant trend after 2007 (trend change: −3.1%; 95%CI −4.7, −1.6). Hospitalization rates remained at approximately 37% from 2002 to 2007 but declined to 25.7% by 2015 (trend change: −2.2%; 95%CI −3.0, −1.4). Similar trend changes occurred among control conditions versus syncope, including advanced imaging for headache (difference in trend change: −0.6%; 95%CI −2.8, 1.6) and hospitalizations for chest pain, dysrhythmia, and pneumonia (differences in trend changes: 0.1% [95%CI −1.9, 2.0]; −0.9% [95%CI −3.1, 1.3]; and −1.2% [95%CI −5.3, 2.9], respectively). ConclusionsBefore and after the release of 2007 ACEP syncope guidelines, trends in advanced imaging and hospitalization for ED syncope visits had similar changes compared to control conditions. Changes in syncope care may, therefore, reflect broader practice shifts rather than a direct association with the 2007 ACEP guideline. Moreover, utilization of advanced imaging remains prevalent. To reduce low-value care, policymakers should augment society guidelines with additional policy changes such as reportable quality measures.

The “efficacy paradox”

The “efficacy paradox” occurs when the efficacy of a treatment in a randomised controlled trial (RCT), or the recommendation in an evidence-based guideline, differs from the treatment benefits seen in clinical practice (1–3). This occurs because in RCT reporting and guidelines, treatment efficacy is judged by the difference in outcome between treatment and placebo (i.e., the specific effect of the treatment). This difference is used to estimate the “strength” or effect size (ES) of a treatment, and only treatments that separate from placebo by a minimum clinically important difference (MCID) may be recommended for use (e.g., by NICE). However, RCT participants who receive placebo often do very well, and in the treatment group the overall treatment ES (which includes both specific and contextual responses) is often in the good-strong range of ES. When a patient receives a treatment in practice it is the overall treatment effect, not just the specific treatment effect that they experience. This difference in focus can cause discordance between guidelines and clinical practice and ignores the impact of contextual response in clinical care (1). An alternative way of reporting RCTs is to firstly highlight the overall treatment effect (as would be expected in practice), and then explain how much of this is attributable to specific treatment effect and how much to placebo/contextual effects (the “proportional contextual effect (PCE)” (2)). This interpretation of all the results would diminish the paradox, alter the hierarchy of “strong treatments” for individual conditions (based on overall treatment rather than just specific treatment effects), and might lead to changes in guideline recommendations. For many chronic painful distressing conditions (e.g., OA, fibromyalgia) the majority of treatment benefit results from contextual effects, and optimising such effects in clinical practice could lead to substantial improvements in patient-centred outcomes. 1. Walach H. J Altern Complement Med 2001;7(3):213–218. 2. Zhang et al. Ann Intern Med 2015;163:392–393. 3. Zhang W, Doherty M. Clin Immunol 2017. https://doi.org/10.1016/j.clim.2017.07.018.

The impact of emerging safety and effectiveness evidence on the use of physician-administered drugs: the case of bevacizumab for breast cancer.

Spending on physician-administered drugs is high and uses not approved by the US Food and Drug Administration (FDA) are frequent. Although these drugs may be targets of future policy efforts to rationalize use, little is known regarding how physicians respond to emerging safety and effectiveness evidence. We analyzed changes in bevacizumab (Avastin) use for breast cancer in response to its market launch (February 2008), 2 FDA meetings reviewing data suggesting that its risks exceed its benefits (July 2010 and June 2011), and the FDA's withdrawal of approval (November 2011). Data from a population-based audit of oncologists' prescribing (IntrinsiQ Intellidose) were used to measure the monthly number of breast cancer patients treated with bevacizumab (January 2008-April 2012). The number of bevacizumab patients following each regulatory action was estimated using negative binomial regression, compared with patients before the first FDA meeting, adjusting for cancer stage, treatment line, patient age, and outpatient office affiliation. Bevacizumab use for breast cancer increased significantly after FDA approval. After all regulatory actions, there was a 65% decline (95% CI, 64%-65%) in use compared with the period before the first meeting. The largest decline was in the 6-month period after the first meeting (37%; 95% CI, 28%-47%). The rate of decline did not differ by patient or cancer characteristics and differed minimally by office affiliation. Bevacizumab use for breast cancer declined dramatically after FDA meetings and regulatory actions, a period without changes in guideline recommendations or insurance coverage. Physicians seem to be responsive to emerging evidence concerning physician-administered drug safety and effectiveness.

Diabetes screening with hemoglobin A1c prior to a change in guideline recommendations: prevalence and patient characteristics.

BackgroundIn January 2010, the American Diabetes Association recommended the use of hemoglobin A1c (Hgb A1c) to screen and diagnose diabetes. This study explored the prevalence and clinical context of Hgb A1c tests done for non-diabetic primary care patients for the three years prior to the release of the new guidelines. We sought to determine the provision of tests in non-diabetic patients age 19 or over, patients age 45 and over (eligible for routine diabetes screening), the annual change in the rate of this screening test, and the patient characteristics associated with the provision of Hgb A1c screening.MethodsWe conducted a retrospective study using data routinely collected in Electronic Medical Records. The participants were thirteen community-based family physicians in Toronto, Ontario. We calculated the proportion of non diabetic patients who had at least one Hbg A1c done in three years. We used logistic generalized estimating equation with year treated as a continuous variable to test for a non-zero slope in yearly Hbg A1c provision. We modelled screening using multivariable logistic regression.ResultsThere were 11,792 non-diabetic adults. Of these, 1,678 (14.2%; 95%CI 13.6%-14.9%) had at least one Hgb A1c test done; this was higher for patients 45 years of age or older (20.2%; 95% CI 19.3% - 21.2%). The proportion of non-diabetic patients with an A1c test increased from 5.2% in 2007 to 8.8% in 2009 (p < 0.0001 for presence of slope). Factors associated with significantly greater adjusted odds ratios of having the test done included increasing diastolic blood pressure, increasing fasting glucose, increasing body mass index, increasing age, as well as male gender and presence of hypertension, but not smoking status or LDL cholesterol. Patients living in the highest income quintile neighbourhoods had significantly lower odds ratios of having this test done than those in the lowest quintile (p < 0.001).ConclusionsA large and increasing proportion of the non-diabetic patients we studied have had an Hgb A1c for screening prior to guidelines recommending the test for this purpose. Several risk factors for cardiovascular disease or diabetes were associated with the provision of the Hgb A1c. Early uptake of the test may represent appropriate utilization.

Impact of National Clinical Guideline Recommendations for Revascularization of Persistently Occluded Infarct-Related Arteries on Clinical Practice in the United States

The Occluded Artery Trial (OAT) was a large, randomized controlled trial published in 2006 that demonstrated no benefit to routine percutaneous coronary intervention (PCI) of persistently totally occluded infarct-related arteries (IRA) identified a minimum of 24 hours (on calendar days 3-28) after myocardial infarction (MI). The purpose of this study was to determine the impact of OAT results and consequent change in guideline recommendations for PCI for treatment of persistently occluded IRAs. We identified all patients enrolled in the CathPCI Registry, from 2005 to 2008, undergoing catheterization more than 24 hours after MI with a totally occluded native coronary artery and no major OAT exclusion criteria. We examined trends in monthly rates of PCI for occlusions after OAT publication and after guideline revisions. Because reporting of diagnostic catheterizations was not mandatory, we examined trends among hospitals in the highest quartile for reporting of diagnostic procedures. A total of 28,780 patient visits from 896 hospitals were included. Overall, we found no significant decline in the adjusted monthly rate of PCI of occlusions after publication of OAT (odds ratio [OR], 0.997; 95% confidence interval [CI], 0.989-1.006) or after guideline revisions (OR, 1.007; 95% CI, 0.992-1.022). Among hospitals consistently reporting diagnostic catheterizations, there was no significant decline after OAT publication (OR, 1.018; 95% CI, 0.995-1.042), and there was a trend toward decline after guideline revisions (OR, 0.963; 95% CI, 0.920-1.000). These findings suggest that the results of OAT and consequent guideline revisions have not, to date, been fully incorporated into clinical practice in a large cross-section of hospitals in the United States.

A Virtuous Cycle to Improve Hypertension Outcomes at a National Level

Compared with the seemingly orderly approach to science associated with controlled laboratory environments, the assessment of broad changes in clinical practices and their impact on society is maddeningly complex and difficult to ascertain with confidence. Yet, in the end, the favorable regard of most societies toward public funding of biomedical science hinges on the belief that the end product of such research will benefit human health. This critical societal trust has been eroded by a growing skepticism directed toward the biomedical research enterprise and its associated industries, particularly the pharmaceutical industry. In this issue of Hypertension , Campbell et al1 report on their analysis of the impact of a program to improve the treatment of hypertension across Canada, one that has corresponded with increased use of antihypertensive medications and reduced incidence of death, stroke, myocardial infarction, and heart failure. The authors took advantage of the confluence of a major change in guideline recommendations, concerted national efforts linking professional societies and public health to control hypertension, and excellent sources of public data. These data allowed them to track prescriptions written by Canadian physicians and to correlate them with rates of key events (death and major cardiovascular and neurologic events) in the overall population. Using the powerful statistical technique of time series analysis, they demonstrated that rates of these critical events declined in direct proportion to the increase in prescription of antihypertensive medications, beginning in 1999. Taken at face value, this study provides compelling evidence that broad changes in medical care, when supported by convincing evidence from clinical trials, can result in improvements in death and disability for populations at the national level. Skeptics will …

Inhaled beclomethasone versus budesonide for chronic asthma.

Beclomethasone dipropionate (BDP) and budesonide (BUD) are used widely in the treatment of chronic asthma. The two drugs have different in vitro pharmacokinetic characteristics. It is unclear whether this translates into clinically significant differences in efficacy or safety when treating children and adults with chronic asthma. To assess clinical outcomes in studies which have compared inhaled BDP and BUD in the treatment of chronic asthma. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999). Prospective, randomised trials comparing BDP to BUD in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1. 24 studies met the criteria for inclusion (1174 subjects). Methodological quality was variable. A meta-analysis of crossover studies did not demonstrate a significant difference between BDP and BUD for FEV1, morning PEF, evening PEF, asthma symptoms or rescue beta2 agonist use, over a dose range of 400 to 1000 mcg/d. The majority of crossover trials had significant design flaws related to a lack of washout and/or failure to exclude carryover effects so the results must be viewed with caution. A single crossover study with adequate washout showed that BUD 400 mcg/d delivered via Turbohaler dry powder inhaler (DPI) may be more effective than BDP 400 mcg/d delivered via Rotahaler DPI in reducing histamine bronchial hyper-responsiveness: Weighted Mean Difference (WMD) 0.43 log10 PC20 FEV1 (95% Confidence Intervals (CI) 0.05, 0.81 log10 PC20 FEV1). A meta-analysis of two parallel group, dose down-titration studies (231 patients) showed that less BUD delivered via a Turbohaler DPI was required to maintain control in adults asthmatics compared to BDP delivered via metered dose inhaler with or without a spacer: WMD 444 mcg/d (95% CI 332, 556 mcg/d). There is limited high quality randomised controlled trial data comparing the relative efficacy of BDP and BUD. Current guidelines (BTS 1997, GINA 1995, NHLBI 1997) assume BDP and BUD to have equal efficacy, such that for each defined level of asthma severity, the recommended doses BDP and BUD are the same. Although there is some data to suggest that BUD via Turbohaler is more effective than BDP via either Rotahaler or MDI (with and without spacer), these comparisons are confounded by use of different delivery devices, and are not sufficient to warrant a change in guideline recommendations.