Title: Prescription Trends of Hydrochlorothiazide vs. Chlorthalidone in the United States (2019-2024).

Alterations in surgical technique after FDA statement on power morcellation

BackgroundA see on cardiovascular diseases and bladder cancer. The changes to the patterns of rosiglitazone and pioglitazone utilisation in Australia following the timing of these various health authority warnings such as the Australian Therapeutic Good Administration (TGA), European Medicines Agency (EMA) press releases or U.S. Food and Drug Administration (FDA) is unknown. This study investigated the utilisation patterns of rosiglitazone and pioglitazone in Australia before and after warnings of major drug authorities.MethodsWe evaluated rosiglitazone and pioglitazone dispensing using the Pharmaceutical Benefit Scheme (PBS) subsidised drug dispensing data for the Australian population from February 2004 to July 2012. The World Health Organisation Anatomic Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) system was used to compare the drug utilisation patterns following the announcements of EMA, FDA, and TGA safety warnings, which first occurred in May 2007. The DDD/1000population/day were examined in a series of time-series regression analysis with the drug safety warnings specified as interventions.ResultsRosiglitazone utilisation increased steadily from 2004 until reaching a peak at 1.96/1000population/day in January 2007. Then rosiglitazone use decreased significantly after the initial EMA press release and FDA warning on cardiovascular risk in May 2007 (with a 15.04% average monthly decline, p-value <0.001), however use did not significantly decrease after the TGA warning or subsequent EMA and FDA warnings. Pioglitazone utilisation proceeded rosiglitazone in September 2008 and remained above 1.5/1000/day during 2009–2010. However, pioglitazone utilisation has slightly declined after the FDA, EMA, and TGA warnings related to bladder cancer.ConclusionsDrug safety warnings were associated with a decrease in rosiglitazone and pioglitazone utilisation in Australia. Rosiglitazone began to decline prior to TGA warnings in December 2007, which suggests that Australian prescribers may have acted in response to scientific evidence or international safety warnings (EMA, FDA), prior to the response of the TGA. Minor effects were observed after bladder cancer warnings on pioglitazone utilisation.

While US Food and Drug Administration (FDA) black box warnings are common, their impact on perioperative outcomes is unclear. Hydroxyethyl starch (HES) is associated with increased bleeding and kidney injury in patients with sepsis, leading to an FDA black box warning in 2013. Among patients undergoing musculoskeletal surgery in a subset of hospitals where colloid use changed from HES to albumin following the FDA warning, we examined the rate of major perioperative bleeding post- versus pre-FDA warning. The authors of this article used a retrospective, quasi-experimental, repeated cross-sectional, interrupted time series study of patients undergoing musculoskeletal surgery in hospitals within the Premier Healthcare Database, in the year before and year after the 2013 FDA black box warning. We examined patients in 23 "switcher" hospitals (where the percentage of colloid recipients receiving HES exceeded 50% before the FDA warning and decreased by at least 25% in absolute terms after the FDA warning) and patients in 279 "nonswitcher" hospitals. Among patients having surgery in "switcher" and "nonswitcher" hospitals, we determined monthly rates of major perioperative bleeding during the 12 months after the FDA warning, compared to 12 months before the FDA warning. Among patients who received surgery in "switcher" hospitals, we conducted a propensity-weighted segmented regression analysis assessing differences-in-differences (DID), using patients in "nonswitcher" hospitals as a control group. Among 3078 patients treated at "switcher" hospitals (1892 patients treated pre-FDA warning versus 1186 patients treated post-FDA warning), demographic and clinical characteristics were well-balanced. Two hundred fifty-one (13.3%) received albumin pre-FDA warning, and 900 (75.9%) received albumin post-FDA warning. Among patients undergoing surgery in "switcher" hospitals during the pre-FDA warning period, 282 of 1892 (14.9%) experienced major bleeding during the hospitalization, compared to 149 of 1186 (12.6%) following the warning. In segmented regression, the adjusted ratio of slopes for major perioperative bleeding post- versus pre-FDA warning was 0.98 (95% confidence interval [CI], 0.93-1.04). In the DID estimate using "nonswitcher" hospitals as a control group, the ratio of ratios was 0.93 (95% CI, 0.46-1.86), indicating no significant difference. We identified a subset of hospitals where colloid use for musculoskeletal surgery changed following a 2013 FDA black box warning regarding HES use in sepsis. Among patients undergoing musculoskeletal surgery at these "switcher" hospitals, there was no significant decrease in the rate of major perioperative bleeding following the warning, possibly due to incomplete practice change. Evaluation of the impact of systemic changes in health care may contribute to the understanding of patient outcomes in perioperative medicine.

Research round-up

ObjectiveTo describe the pattern of hydroxychloroquine use and examine the association between hydroxychloroquine use and clinical outcomes arising from changes in the US Food and Drug Administration (FDA)’s recommendation during...

Objective: To evaluate national trends in incident varenicline and nicotine replacement therapy (NRT) prescribing among Department of Veterans Affairs (VA) beneficiaries before and after US Food and Drug Administration (FDA) warnings regarding neuropsychiatric side effects with varenicline use. Methods: All adult VA patients identified as smokers from 2007 to 2019 (N = 3,600,947) were determined and monthly counts of new varenicline and NRT users were calculated. An interrupted time-series analysis estimated the effect of the FDA warnings on varenicline and NRT prescribing overall and among Veterans with and without mental health disorders. Results: The incident use rate of varenicline decreased from a peak of 6.2 per 1,000 veteran smokers in October 2007 to 1.0 by July 2009 following the first FDA warning (pre-warning monthly slope = −0.27; P = .03). New NRT use increased from 10.7 per 1,000 veteran smokers in October 2007 to a peak of 12.6 per 1,000 in July 2009 (slope change = 0.71; P = .01), suggesting potential substitution. Following removal of the FDA boxed warning in December 2016, varenicline prescribing increased but did not return to pre-warning levels by December 2019. Among veterans with and without mental health disorders, varenicline use decreased 90% and 88%, respectively, following the first FDA warning, and both groups had comparable rates of new NRT use. Conclusions: Following the first FDA warning, incident use of varenicline declined significantly among veterans both with and without mental health disorders. Despite removal of the FDA boxed warning in December 2016, new use of varenicline had not returned to pre-warning levels 3 years following the removal.

Biotin interference in routine laboratory tests: A bibliometric analysis

In 2013 and 2016, the US Food and Drug Administration (FDA) issued warnings and recommended limited use of fluoroquinolones for patients with certain acute conditions. It is not clear how prescribers have responded to these warnings. To analyze changes in prescribing of fluoroquinolones after the 2013 and 2016 FDA warnings and to examine the physician characteristics associated with these changes. This cross-sectional study used Medicare administrative claims data on Medicare fee-for-service beneficiaries and OneKey data on physicians and their organizations from January 1, 2011, to December 31, 2017. The sample was restricted to outpatient visits for sinusitis, bronchitis, and uncomplicated urinary tract infections. An interrupted time series approach was used to analyze the changes in the prescription rate after each FDA warning. Data analysis was performed between January 1, 2011, and December 31, 2017. Two FDA black box warnings released in August 2013 and July 2016. The main outcome was an indicator for fluoroquinolone prescriptions in 3 periods: before the 2013 warning (baseline period), after the 2013 warning but before the 2016 warning (postwarning period 1), and after the 2016 warning (postwarning period 2). The sample comprised 1 238 397 unique patients with a total of 2 720 071 outpatient acute care visits. Of this sample, 848 360 were women (68.5%), and the mean (SD) age was 69.7 (12.6) years. The immediate prescribing levels of fluoroquinolones in postwarning period 1 increased by 3.42 percentage points (95% CI, 3.23-3.62; P < .001) and declined by -0.77 percentage points (95% CI, -1.00 to -0.54; P < .001) in postwarning period 2. The prescribing trend increased by 0.08 percentage points per month (95% CI, 0.08-0.10; P < .001) in postwarning period 1 and 0.06 percentage points per month (95% CI, 0.04-0.08; P < .001) in postwarning period 2. In postwarning period 1, the prescribing levels for physicians who were affiliated with hospitals with a top 10th percentile case mix index vs those without such affiliation decreased by -1.13 percentage points (95% CI, -1.92 to -0.34; P = .005), whereas the levels for primary care physicians declined by -1.34 percentage points (95% CI, -1.78 to -0.88; P < .001) compared with non-primary care physicians in postwarning period 2. Physicians at teaching hospitals were the only ones who showed a decline in prescribing trend in postwarning period 1. This cross-sectional study found an overall decline in prescribing of fluoroquinolones after the release of FDA warnings. Understanding the association of physician and organizational characteristics with fluoroquinolone prescribing behavior may ultimately help to identify mechanisms to improve de-adoption.

Evaluation of: Zivin K, Pfeiffer PN, Bohnert AS, Ganoczy D, Blow FC, Nallamothu BK, Kales HC. Evaluation of the FDA Warning against Prescribing Citalopram at Doses Exceeding 40 mg. Am J Psychiatry. 2013 May 3. doi: 10.1176/appi.ajp.2013.12030408. [Epub ahead of print]A number of studies have suggested that antidepressants such as selective serotonin reuptake inhibitors may increase a risk of developing harmful cardiac adverse event such as QT interval prolongation. In fact, the US Food and Drug Administration (FDA) consecutively gave safety warnings to healthcare professionals that the use of citalopram may be associated with QT interval prolongation in 2011 and 2012. Despite the fact that citalopram has been one of the most acceptable antidepressants worldwide, concerns on citalopram about cardiac safety issues have become apparent to clinicians after the FDA warning. However, a recent cohort study raises some practical questions about the FDA warnings on the use of citalopram and may also provide clinicians with a good guidance for prudent use of citalopram in clinical practice.

Over half of adults in the United States report consuming dietary supplements. The US Food and Drug Administration (FDA) has warned of numerous dietary supplements containing undeclared, unapproved pharmaceutical ingredients. These FDA warnings have not been comprehensively analyzed for recent years. To summarize trends across adulterated (containing unapproved ingredients) dietary supplements associated with a warning released by the FDA from 2007 through 2016. In this quality improvement study, data were extracted from the FDA's Center for Drug Evaluation and Research, Tainted Products Marketed as Dietary Supplements_CDER database from 2007 through 2016. Data from each warning were recorded unless multiple warnings were issued for the same product within a 6-month period. Date, product name, company, hidden ingredient(s), product category, source of sample, and warning document type were recorded for each included warning. Data analysis was conducted from February 2017 to June 2017. From 2007 through 2016, 776 adulterated dietary supplements were identified by the FDA and 146 different dietary supplement companies were implicated. Most of these products were marketed for sexual enhancement (353 [45.5%]), weight loss (317 [40.9%]), or muscle building (92 [11.9%]), with 157 adulterated products (20.2%) containing more than 1 unapproved ingredient. The most common adulterants were sildenafil for sexual enhancement supplements (166 of 353 [47.0%]), sibutramine for weight loss supplements (269 of 317 [84.9%]), and synthetic steroids or steroid-like ingredients for muscle building supplements (82 of 92 [89.1%]). There were 28 products named in 2 or 3 warnings more than 6 months apart. Of these products, 19 (67.9%) were reported to contain new unapproved ingredients in the second or third warning, consistent with the assumption that the FDA found the product to be adulterated more than once. In recent years (2014-2016), 117 of 303 adulterated samples (38.6%) were identified through online sampling and 104 of 303 (34.3%) were identified through the examination of international mail shipments. Active pharmaceuticals continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after FDA warnings. The drug ingredients in these dietary supplements have the potential to cause serious adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement.

Pharmacy Data Shed More Light on Antidepressant Trends

The Food and Drug Administration (FDA) has issued more than 350 safety alerts for drugs and biological products, since January 2008. Approximately 12% (40) of these alerts were regarding medications indicated for the treatment of neurologic or psychiatric disorders. FDA safety alerts are intended to improve patient safety by providing the medical community with timely new safety data and actionable information that may impact treatment choices by both healthcare providers and patients. Communication of the safety alert to health care professionals also generally provides a summary of the data that serves as the basis for the alert, although often unpublished and not accessible for in depth review by decision makers. Health care providers and institutions are expected to orchestrate a response to these alerts that is in the best interest of delivering safe care to patients. Responses may range from dissemination of new information, policy development, or changes in selection or use of a drug or medication class. As mental health care delivery systems vary widely in size, patient population, infrastructure and financing, and resources (personnel and technology), responses to safety alerts may also vary to same degree. We were interested in identifying commonalities for failures and successes, in the experiences of clinical pharmacy specialists in mental health settings responding to safety alerts.

Droperidol-induced Proarrhythmia

The US Food and Drug Administration (FDA) is a remarkable hybrid. Part regulatory agency, part public health agency, it sits at the intersection of science, law, and public policy. The FDA’s mission can be considered in the context of 2 broad dimensions: the products it regulates and its core functions. Both fall under the rubric of protecting and promoting the public health. The FDA’s remit is both broad and diverse: altogether, the agency has regulatory responsibility for >20% of the US economy. The products it is charged with overseeing through its various centers1 encompass food and cosmetics (regulated by the Center for Food Safety and Applied Nutrition); food and drugs for animals, including companion animals and animals used for food (regulated by the Center for Veterinary Medicine); and medical devices, drugs, and biologics (regulated by the Centers for Devices and Radiological Health, Drug Evaluation and Research, and Biologics Evaluation and Research, respectively). Tobacco products were added to the FDA’s portfolio by the Tobacco Control Act of 2009, and are overseen by the Center for Tobacco Products. Regardless of the specific product regulated, the FDA’s core mission remains the same: to protect the US population by helping to ensure the fundamental safety of the food Americans consume and the medical products prescribed by their clinicians. At the same time, this primary mission is complemented by a mandate to promote the public health by reviewing research and taking appropriate action on the marketing of regulated products in a timely manner. Not only do people need access to advances in nutrition and medical therapies, but also the American spirit is itself characterized by a strong current of scientific and technological innovation. At first glance, differences in these 2 priorities, protecting the public safety and promoting the public health through encouraging innovation, might …

Direct-Acting Antivirals for Chronic Hepatitis C: Can Drug Properties Signal Potential for Liver Injury?