Drug Administration Warnings Research Articles

Ultra Long-term Follow-up of the Autologous Pubovaginal Sling for Stress Incontinence: Results at 23 Years

To examine the efficacy, safety, and long-term durability of the autologous pubovaginal sling for stress incontinence over a 29-year period. A total of 192 consecutive female patients with stress urinary incontinence who underwent autologous pubovaginal sling from 1993 through 1999 were analyzed over a 29-year period. Intermediate and ultra long-term follow-up were obtained at a mean of 4 and 23years, respectively. A total of 51 patients had sufficient data at both time intervals and were evaluated using a standardized questionnaire for resolution of stress incontinence, the primary endpoint, as well as resolution of urge incontinence, overall dryness, and voiding dysfunction. At intermediate-term follow-up (mean 45.3months), 96% of 51 patients reported no stress incontinence. In addition, 76% of patients experienced resolution of their preoperative urge incontinence. Overall dryness occurred in 84%. At ultra long-term follow-up (mean 22.9years), 84% reported no stress incontinence and an overall dryness rate of 53%. Postoperative voiding dysfunction included de novo urge incontinence (3 patients) and persistent urinary obstruction requiring urethrolysis (1 patient). The autologous pubovaginal sling is effective, safe, and durable at a mean of 23years, the longest known follow-up in the literature. Given the U.S. Food and Drug Administration (FDA) warnings regarding transvaginal mesh and growing concerns with the synthetic midurethral sling, the autologous pubovaginal sling should be offered as an option to those women seeking treatment for stress urinary incontinence.

Loperamide cases reported to United States poison centers, 2010–2022

BackgroundIntentional use of high doses of loperamide has been linked to serious cardiac toxicity. The objective of this study is to investigate the characteristics and trends of loperamide cases reported to United States (US) poison centers and to evaluate the changes in reported loperamide cases following US Food and Drug Administration (FDA) warnings, labeling requirements, and packaging restrictions for loperamide starting in 2016, with an emphasis on intentional exposures.MethodsData from the National Poison Data System were analyzed.ResultsThere were 12,987 cases reported to US poison centers from 2010 to 2022, for which, loperamide was the most likely substance responsible for observed clinical effects. Although 46.1% of these cases were associated with minor or no effect, 13.4% resulted in a serious medical outcome, including 59 deaths (0.5%). Eight percent (8.1%) of cases were admitted to a critical care unit and 5.0% were admitted to a non-critical care unit. Among cases with a serious medical outcome, most were associated with loperamide abuse (38.0%), intentional-misuse (15.7%), or suspected suicide (27.5%). The majority (60.0%; n = 33) of fatalities were related to abuse, followed by suspected suicide (20.0%; n = 11) and intentional-misuse (5.5%, n = 3). The rate of loperamide cases per 100,000 US population reported to US PCs decreased from 0.44 in 2010 to 0.36 in 2015 (p = 0.0290), followed by an increase to 0.46 in 2017 (p = 0.0013), and then a trend reversal with a decrease to 0.28 in 2022 (p < 0.0001). The rate of serious medical outcomes related to loperamide increased from 0.03 in 2010 to 0.05 in 2015 (p = 0.0109), which subsequently increased rapidly to 0.11 in 2017 (p < 0.0001), and then demonstrated a trend reversal and decreased to 0.04 in 2022 (p < 0.0001).ConclusionsFDA warnings, labeling requirements, and packaging restrictions may have contributed to the observed trend reversal and decrease in reports to US poison centers of loperamide cases related to intentional misuse, abuse, and suspected suicide. This demonstrates the potential positive effect that regulatory actions may have on public health. These findings contribute to the evidence supporting the application of similar prevention efforts to reduce poisoning from other medications associated with intentional misuse, abuse, and suicide.

An Updated Review of Food and Drug Administration Warning and Untitled Letters for Clinical Outcome Assessment Claims Between 2013 and 2021

ObjectivesWe aimed to ascertain the frequency and types of Food and Drug Administration (FDA)-identified clinical outcome assessment (COA) violations in US pharmaceutical promotional materials from 2013 to 2021 by updating the review by Symonds et al (covering the period 2006-2012 for patient-reported outcomes [PRO] measures), expanding to infringements across all types of COAs, and grouping by efficacy or overall patient experience. MethodsWarning letters (WLs) and untitled letters (ULs) issued by the FDA’s Office of Prescription Drug Promotion were reviewed for COA violations and classified by their type: (1) COA measure not fit for purpose, (2) issue with study design or interpretation of results, and (3) inadequate statistical analysis. ResultsFrom 2013 to 2021, the FDA issued 22 WLs and 65 ULs. Year 2013 showed the highest number of letters issued (n = 24). Of the total 87 letters reviewed, 22 (25%) contained a COA violation, consisting of 6 WLs (27%) and 16 ULs (25%), including 20 (23%) with a PRO-related violation. The most common violations cited “study design or interpretation of results” (21 of 22 [95%]). ConclusionsOverall, the absolute number of WLs and ULs issued declined when comparing 2006 to 2012 with 2013 to 2021. Despite the overall reduction, this review still identified 25% of letters citing COA infringements (23% with PRO issues), which was similar to the prior review (19% PRO infringements). This may be due to increased FDA attention to patient-focused drug development.

Change in Pediatric Adenotonsillectomy Postoperative Visit Patterns After Opioid Food and Drug Administration Warning.

This study aimed to determine the association between opioid prescriptions given after tonsillectomy with adenoidectomy (T + A) and pain-related return visit rates in pediatric patients. Determine association between Food and Drug Administration (FDA) black box warning against opioid use in this population and pain-related return visit rates. This was a single-institution retrospective cohort study of pediatric patients who underwent T + A between April 2012 and December 2015 and had return visits to the emergency department or urgent care center. Data were obtained from the hospital electronic warehouse using International Classification of Diseases-9/10 procedure codes. Odds ratios (ORs) with 95% confidence intervals (CIs) for return visits were calculated. Multivariate logistic regression analysis was used to measure association between opioid prescriptions and return visit rates as well as FDA warning and return visit rates adjusting for confounders. There were 4778 patients who underwent T + A, median age, 5 years. Of these, 752 (15.7%) had return visits. Pain-related return visits were higher in patients who received opioid prescriptions (adjusted OR, 1.31; 95% CI, 1.09-1.57). After FDA warning, opioids were prescribed at a lower rate (47.9%) compared with previous (98.6%) (OR, 0.01; 95% CI, 0.008-0.02). Pain-related return visits were lower after FDA warning (OR, 0.73; 95% CI, 0.61-0.87). Steroid prescription rate increased after FDA warning (OR, 415; 95% CI, 197-874). Opioid prescriptions were associated with higher pain-related return visits after T + A, whereas issuance of FDA black box warning against codeine use was associated with lower pain-related return visits. Our data suggest that the black box warning potentially had unintended benefits in pain management and health care usage.

Innovative prolapse surgery without mesh implants

In many countries, such as France, England, USA, Canada, Australia, and New Zealand, alloplastic material in prolapse surgery has been paused due to the US Food and Drug Administration (FDA) warning, and restricted in other countries like the Netherlands and Sweden. For Europe and thus Germany, the SCENIHR report allows alloplastic material to be used for prolapse repair after recurrence and in other special situations. Which established and innovative prolapse surgeries without alloplastic material are currently available? Aliterature search was carried out on established, guideline-compliant pelvic floor surgeries without alloplastic material as well as innovative new approaches. An established procedure for adefect in the anterior compartment is anterior colporrhaphy, which is associated with ahigh recurrence rate. The double-layered anterior colporrhaphy is anew approach and so far is associated with an improved 19-month outcome. Apical pelvic organ prolapse can be corrected by sacrouterine ligament fixation and vaginal sacrospinous fixation. New innovative techniques include laparoscopic unilateral pectineal suspension and the use of the semitendinosus tendon autograft to perform pectopexy or sacropexy. However, long-term data are still pending. In case of aposterior vaginal wall prolapse, posterior colporrhaphy is the therapy of choice and is associated with good success rates. Well-known surgical procedures with native tissue are experiencing arenaissance and new, innovative surgical approaches with good postoperative results are being developed. However, long-term studies are still necessary.

Potential Impact of Pharmacogenomic Single Nucleotide Variants in a Rural Caucasian Population.

In the US adverse drug reactions (ADRs) are estimated to cause 100 000 fatalities and cost over $136 billion annually. A patient's genes play a significant role in their response to a drug. Pharmacogenomics aims to optimize drug choice and dose for individual patients by characterizing patients' pharmacologically relevant genes to identify variants of known impact. DNA was extracted from randomly selected remnant whole blood samples from Caucasian patients with previously performed complete blood counts. Samples were genotyped by mass spectrometry using a customized pharmacogenomics panel. A third-party result interpretation service used genotypic results to predict likely individual responses to frequently prescribed drugs. Complete genotypic and phenotypic calls for all tested Cytochrome P450 isoenzymes and other genes were obtained from 152 DNA samples. Of these 152 unique genomic DNA samples, 140 had genetic variants suggesting dose adjustment for at least one drug. Cardiovascular and psychiatry drugs had the highest number of recommendations, which included United States Food and Drug Administration warnings for highly prescribed drugs metabolized by CYP2C19, CYP2C9, CYP2D6, HLA-A, and VKORC1. Risk for each drug:gene pairing primarily depends upon the degree of predicted enzyme impairment or activation, width of the therapeutic window, and whether parent compound or metabolite is pharmacologically active. The resulting metabolic variations range from risk of toxicity to therapeutic failure. Pharmacogenomic profiling likely reduces ADR potential by allowing up front drug/dose selection to fit a patient's unique drug-response profile.

Getting square pegs out through round holes: A survey of Australian and New Zealand Gynaecologists regarding specimen retrieval.

To evaluate morcellation practices among Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). RANZCOG Fellows were invited to complete an online survey. This anonymous, cross-sectional survey consisted of 29 questions regarding demographics and morcellation practices. Four hundred and thirty eight (19.04%) of 2300 RANZCOG Fellows responded, and of these 258 (11.22%) completed the entire survey; analysis was undertaken on data from the latter respondents. Respondents were broadly representative of all RANZCOG Fellows regarding gender, age, and location. Of the respondents, 53.10% considered themselves advanced laparoscopic surgeons. Of respondents who had worked as gynaecology consultants prior to 2014, 39.39% used uncontained power morcellation prior to 2014, compared to 17.58% since (a decrease of 44.63%). The most common reasons for utilising uncontained power morcellation less often were the 2014 Food and Drug Administration warnings (40.31%), risk of adverse outcomes (33.72%), and recommendations from colleges such as RANZCOG (27.13%). When undertaking an operation that required specimen extraction, the most common methods used were: employing an open approach from the get-go (utilised by respondents in 31.01% of such cases); contained manual morcellation (28.90%); and conversion to intra-operative laparotomy (10.10%). There has been a strong trend away from uncontained power morcellation since 2014, with a 36.00% increase in clinicians who never use uncontained power morcellation, and an 80.65% decrease in clinicians who always use this method of specimen extraction. The most common reason cited for employing uncontained power morcellation less often was the 2014 Food and Drug Administration's warnings.

Isotretinoin: Risk or Benefit to Mental Health in Youth?

Isotretinoin is a medication for severe recalcitrant nodular acne and treatment-resistant forms of acne. Despite its effectiveness, adverse events have required U.S. Food and Drug Administration warning and close monitoring; psychiatric warnings include depression, psychosis, suicidal ideation, and suicide. However, longstanding concerns about psychiatric symptoms associated with isotretinoin have been called into question in recent literature. In addition, risk for psychological effects of acne have been recognized independent of treatment. Proper treatment of acne, coupled with mental health screening, provides the best course of action. [Journal of Psychosocial Nursing and Mental Health Services, 60(2), 7-9.].

Trends in Incident Varenicline Prescribing Among Veterans Following the US Food and Drug Administration Drug Safety Warnings.

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.

Single-use Albarran module: A removable elevator system to enhance safety in biliary endoscopy?

Bacterial infections are a major burden in biliary endoscopy. Besides incomplete manual cleaning of endoscopes, hard-to-clean components of duodenoscopes are responsible for a substantial rate of bacterial contamination. A large meta-analysis showed that 15 % of duodenoscopes harbored microorganisms of gastrointestinal or oral origin, independent from the colony forming unit (CFU) count. This indicates that the current reprocessing and process control procedures, even with ethylene oxide (ETO), could be insufficient [1]. Therefore, US Food and Drug Administration (FDA) warnings led companies to redesign duodenoscopes with the aim of enhancing safety. Disposable caps or caps + elevator are available options on the market [2] [3]. Moreover, two disposable duodenoscopes models have recently been approved by the FDA: the Boston Scientifc EXALT Model D and the Ambu A/S Ambu aScope Duodeno. Studies on disposable duodenoscope feasibility and possible economic impact on the market yielded interesting results, although the data are still preliminary [4] [5] [6] [7] [8].

Short term complications in mesh augmented vaginal repair of pelvic organ prolapse are not higher when compared with native tissue repair.

Accumulating evidence regarding the negative long-term consequences of transvaginal mesh-based procedures for pelvic organ prolapse has led to a sharp decline in mesh-based procedures. We aimed to evaluate the short-term complications of mesh-based procedures for carefully selected patients with pelvic organ prolapse after Food and Drug Administration warnings. A retrospective database review of the ACS NSQIP database was completed to examine 30-day complications including re-operation, prolonged length of stay, blood transfusion, surgical site infection, urinary tract infection, readmission and wound dehiscence in mesh-augmented and native tissue-based transvaginal procedures for pelvic organ prolapse. A total of 36,234 patients were included in the analysis, with only 7.1% (2574 women) having mesh-augmented repair. Using a multivariable logistical regression analysis adjusting for confounders, we found that the primary composite outcome (re-operation, hospital stay, blood transfusion and surgical site infection) was less common in the mesh group compared with the native tissue repair group (adjusted OR 0.80, CI 0.67-0.95, p= 0.009). The secondary outcomes (urinary tract infection, re-admission and wound dehiscence) were not different between the group. These results suggest that in well-chosen patients, short-term complications are not increased when using transvaginal mesh for pelvic organ prolapse repair.

Updates on Therapeutic Alternatives for Genitourinary Syndrome of Menopause: Hormonal and Non-Hormonal Managements.

Postmenopausal atrophic vaginitis, along with vasomotor symptoms and sleep disorders, is one of the most troublesome symptoms of menopause. However, many women do not manage this symptom properly due to insufficient knowledge of the symptoms or sexual embarrassment. With appropriate treatment, many postmenopausal women can experience relief from discomforts, including burning sensation or dryness of the vagina and dyspareunia. Topical lubricants and moisturizers, systemic and local estrogens, testosterones, intravaginal dehydroepiandrosterones (DHEAs), selective estrogen receptor modulators, and energy-based therapies are possible treatment modalities. Systemic and local estrogen therapies effectively treat genitourinary syndrome of menopause (GSM), but they are contraindicated in patients with breast cancer, for whom lubricants and moisturizers must be considered as the primary treatment. Intravaginal DHEA and ospemifene can be recommended for moderate to severe GSM; however, there is insufficient data on the use of intravaginal DHEA or ospemifene in patients with breast cancer, and further studies are needed. Energy-based devices such as vaginal laser therapy reportedly alleviate GSM symptoms; however, the U.S. Food and Drug Administration warning has recently been issued because of complications such as chronic pain and burning sensations of the vagina. To summarize, clinicians should provide appropriate individualized treatment options depending on women's past history, symptom severity, and chief complaints.

Enhanced Recovery and Surgical Optimization Protocol for Minimally Invasive Gynecologic Surgery: An AAGL White Paper

This is the first Enhanced Recovery After Surgery (ERAS) guideline dedicated to standardizing and optimizing perioperative care for women undergoing minimally invasive gynecologic surgery. The guideline was rigorously formulated by an American Association of Gynecologic Laparoscopists Task Force of US and Canadian gynecologic surgeons with special interest and experience in adapting ERAS practices for patients requiring minimally invasive gynecologic surgery. It builds on the 2016 ERAS Society recommendations for perioperative care in gynecologic/oncologic surgery by serving as a more comprehensive reference for minimally invasive endoscopic and vaginal surgery for both benign and malignant gynecologic conditions. For example, the section on preoperative optimization provides more specific recommendations derived from the ambulatory surgery and anesthesia literature for the management of anemia, hyperglycemia, and obstructive sleep apnea. Recommendations pertaining to multimodal analgesia account for the recent Food and Drug Administration warnings about respiratory depression from gabapentinoids. The guideline focuses on workflows important to high-value care in minimally invasive surgery, such as same-day discharge, and tackles controversial issues in minimally invasive surgery, such as thromboprophylaxis. In these ways, the guideline supports the American Association of Gynecologic Laparoscopists and our collective mission to elevate the quality and safety of healthcare for women through excellence in clinical practice.

Diagnosis of rupture of membranes: AmniSure, clinical assessment, and the Food and Drug Administration warning

An accurate diagnosis of rupture of membranes is critical to the rendering of appropriate maternity care in both preterm and term patients. Immunoassays, such as the one detecting placental alpha microglobulin-1 (AmniSure) in cervicovaginal secretions, have replaced the traditional speculum-based assessment in some clinical settings; however, the Food and Drug Administration recently issued a warning regarding the potential risks of using the test in isolation. The study aimed to report the performance of AmniSure as a first-line nurse-administered screening test for rupture of membranes in our teaching county hospital obstetrical triage unit and as part of a clinical protocol to diagnose rupture of membranes. We conducted a retrospective secondary analysis of 310 randomly selected term and preterm patients with concern for rupture of membranes screened with the AmniSure test. We systematically reviewed medical records to determine membrane status at the time of the AmniSure test. We calculated test characteristics of the AmniSure test used independently and in conjunction with speculum-based assessment. Of 302 women evaluated for retrospective determination of membrane status at 17 to 41 weeks' gestation (median, 36.6 weeks' gestation), 208 (68.9%) were intact and 94 (31.1%) were ruptured at the time of the AmniSure test using a gold standard of retrospective membrane status determined by medical record review. A total of 4 false-negative AmniSure results and 16 false-positive AmniSure results were identified. The AmniSure test used independently had a sensitivity of 95.7%, specificity of 92.3%, positive predictive value of 84.9%, and negative predictive value of 98.0%. A rupture of membranes protocol combining AmniSure and clinical assessment had a sensitivity of 98.2%, specificity of 99.5%, positive predictive value of 100.0%, and negative predictive value of 100.0%. The AmniSure has a high sensitivity as a first-line nurse-administered screening test for membrane rupture. Consistent with the Food and Drug Administration warning, the sensitivity, specificity, positive predictive value, and negative predictive value are improved when it is used as part of a clinical protocol and not in isolation. Determination of membrane status remains challenging in a small subset of patients, especially those with an equivocal speculum-based assessment; therefore, engaging women in their care and careful follow-up for identifying persistent or recurrent symptoms are required.

Bleeding After Musculoskeletal Surgery in Hospitals That Switched From Hydroxyethyl Starch to Albumin Following a Food and Drug Administration Warning.

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.

Acute Kidney Injury Events in Patients With Type 2 Diabetes Using SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs: A Retrospective Cohort Study

Sodium/glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease and prevent heart failure events. However, SGLT2 inhibitors may increase the risk for acute kidney injury (AKI). Our objective was to assess whether SGLT2 inhibitor use, compared with all other glucose-lowering drugs (oGLDs), is associated with increased rates of AKI. Retrospective cohort study. Adults in Manitoba, Canada, with type 2 diabetes mellitus followed up from June 2014 until March2017. Initial SGLT2 inhibitor or oGLD use ascertained through a province-wide outpatient prescription database. The primary outcome was incident AKI, identified either by an increase in serum creatinine level and/or hospital discharge codes for AKI while taking glucose-lowering drugs (on-treatment approach). A propensity score analysis was used to assemble groups of incident users of SGLT2 inhibitors and a 1:1 matched set of oGLD users. The rate of AKI was compared across matched groups using cause-specific hazards models. Sensitivity analyses considered exposure to be constant throughout follow-up after initiation of the drug treatment (intention-to-treat approach) or incorporated recurrent exposures (new user design). Comparing 4,778 incident users of SGLT2 inhibitors with 4,778 incident users of oGLDs, there were no differences observed in the primary outcome (HR, 0.64; 95% CI, 0.40-1.03; P= 0.06) using an on-treatment approach. In neither set of sensitivity analyses were SGLT2 inhibitors associated with increased risk for AKI. Drug choice may have been related to AKI risk, laboratory data were obtained from clinical care, and changes in adverse event reporting may have followed the US Food and Drug Administration warning. There were insufficient data to compare individual SGLT2 inhibitors. Compared with oGLDs, SGLT2 inhibitors were not observed to be associated with increased risk for AKI in a clinical population-based cohort.

Decreased Outpatient Fluoroquinolone Prescribing Using a Multimodal Antimicrobial Stewardship Initiative.

BackgroundFluoroquinolones are antibiotics prescribed in the outpatient setting, though they have serious side effects. This study evaluates the impact of stewardship interventions on total and inappropriate prescribing of fluoroquinolones in outpatient settings in a large county hospital and health system.MethodsIn an effort to decrease inappropriate outpatient fluoroquinolone usage, a multimodal antimicrobial stewardship initiative was implemented in November 2016. Education regarding the risks, benefits, and appropriate uses of fluoroquinolones was provided to providers in different outpatient settings, Food and Drug Administration warnings were added to all oral fluoroquinolone orders, an outpatient order set for cystitis treatment was created, and fluoroquinolone susceptibilities were suppressed when appropriate. Charts from October 2016, 2017, and 2018 were retrospectively reviewed if the patient encounter occurred in primary care clinics, emergency departments, or urgent care centers within Parkland Health & Hospital System and a fluoroquinolone was prescribed. Inappropriate use was defined as a fluoroquinolone prescription for cystitis, bronchitis, or sinusitis in a patient without a history of Pseudomonas aeruginosa or multidrug-resistant organisms and without drug allergies that precluded use of other oral antibiotics.ResultsTotal fluoroquinolone prescriptions per 1000 patient visits decreased significantly by 39% (P < .01), and inappropriate fluoroquinolone use decreased from 53% to 34% (P < .01). More than 90% of inappropriate fluoroquinolone prescriptions were given for cystitis, while bronchitis and sinusitis accounted for only 4.4% and 1.6% of inappropriate indications, respectively.ConclusionA multimodal stewardship initiative appears to effectively reduce both total and inappropriate outpatient fluoroquinolone prescriptions.

Sedation, Analgesia, and Neuromuscular Blockade: An Assessment of Practices From 2009 to 2016 in a National Sample of 66,443 Pediatric Patients Cared for in the ICU.

To describe the pharmaceutical management of sedation, analgesia, and neuromuscular blockade medications administered to children in ICUs. A retrospective analysis using data extracted from the national database Health Facts. One hundred sixty-one ICUs in the United States with pediatric admissions. Children in ICUs receiving medications from 2009 to 2016. Frequency and duration of administration of sedation, analgesia, and neuromuscular blockade medications. Of 66,443 patients with a median age of 1.3 years (interquartile range, 0-14.5), 63.3% (n = 42,070) received nonopioid analgesic, opioid analgesic, sedative, and/or neuromuscular blockade medications consisting of 83 different agents. Opioid and nonopioid analgesics were dispensed to 58.4% (n = 38,776), of which nonopioid analgesics were prescribed to 67.4% (n = 26,149). Median duration of opioid analgesic administration was 32 hours (interquartile range, 7-92). Sedatives were dispensed to 39.8% (n = 26,441) for a median duration of 23 hours (interquartile range, 3-84), of which benzodiazepines were most common (73.4%; n = 19,426). Neuromuscular-blocking agents were dispensed to 17.3% (n = 11,517) for a median duration of 2 hours (interquartile range, 1-15). Younger age was associated with longer durations in all medication classes. A greater proportion of operative patients received these medication classes for a longer duration than nonoperative patients. A greater proportion of patients with musculoskeletal and hematologic/oncologic diseases received these medication classes. Analgesic, sedative, and neuromuscular-blocking medications were prescribed to 63.3% of children in ICUs. The durations of opioid analgesic and sedative medication administration found in this study can be associated with known complications, including tolerance and withdrawal. Several medications dispensed to pediatric patients in this analysis are in conflict with Food and Drug Administration warnings, suggesting that there is potential risk in current sedation and analgesia practice that could be reduced with practice changes to improve efficacy and minimize risks.

Contemporary Trends in Prescription of Dipeptidyl Peptidase-4 Inhibitors in the Context of US Food and Drug Administration Warnings of Heart Failure Risk

Dipeptidyl peptidase-4 inhibitors (DPP-4i) are one of the most widely used antihyperglycemic therapeutic classes in type 2 diabetes mellitus management. In April 2016 and August 2017, the US Food and Drug Administration (FDA) introduced sequential labelling requirements regarding heart failure risk related to DPP-4i. We explored longitudinal trends in prescription of DPP-4i before and after these FDA warnings in a multicenter health system. We identified all first-time prescriptions of DPP4i or their combinations across the Partners HealthCare system (Boston, MA) from October 2006 (FDA approval of first DPP-4i) to December 2018. Overall, 11,830 patients were newly prescribed DPP-4i during the study period. Primary care physicians (31.5%) were the most common prescribing specialty. Overall, 8.4%, 20.4%, and 11.6% had heart failure, atherosclerotic cardiovascular disease, and chronic kidney disease, respectively. Median number of background antihyperglycemic therapies was 2 [25th to 75th percentiles 1 to 2], commonly metformin (65.4%) and/or insulin (36.4%). The vast majority of prescriptions were sitagliptin (85.7%), followed by linagliptin (9.5%), saxagliptin (4.7%), and alogliptin (0.2%). Quarterly prescriptions rose gradually from 2006 to mid-2016, and have decreased consistently since then for each of the 4 DPP-4i. Declines in DPP-4i among high-risk groups and those initiated by endocrinologists were most pronounced. In conclusion, although DPP-4i remain a dominant oral antihyperglycemic therapy in clinical practice, new prescriptions have declined recently. These data may reflect relatively swift health system response to broad FDA safety communications regarding heart failure risk, which appeared to impact the entire DPP-4i class, including specific drugs that have not demonstrated any increased risk of heart failure.

Medicolegal Issues in Power Morcellation: Cautionary Rules for Gynecologists to Avoid Unfavorable Outcomes

Power morcellation in laparoscopic surgery enables specialists to carry out minimally invasive procedures such as hysterectomies and myomectomies by cutting specimens into smaller pieces using a rotating blade and removing pieces through a laparoscope. Unexpected uterine sarcoma treated by surgery involving tumor disruption could be associated with poor prognosis. The current study aims to shed light on power morcellation from a medicolegal perspective: the procedure has resulted in adverse outcomes and litigation, and compensation for plaintiffs, as published in various journals cited in PubMed and MEDLINE, Cochrane Library, EMBASE, and GyneWeb. Considering the claims after the US Food and Drug Administration warnings on morcellation, the current study broadens the scope of research by including search engines, legal databases, and court filings (DeJure, Lexis Nexis, Justia, superior court of New Jersey, and US district court of Minnesota) between 1995 and 2019. Legal records show that courts determine professional responsibility regarding complications, making it essential to document adherence to safety protocols and specific guidelines, when available. Sound medical practices and clearly stated institute best practices result in better patient outcomes and are important when unfavorable clinical outcomes occur; adverse legal decisions can be avoided if there are grounds to prove professional conformity with specific guidelines and the unpredictability of an event.