Introduction Although many clinical guidelines caution against the combined use of opioids and benzodiazepines, overdose deaths and emergency department visits involving the co-ingestion of these ...drugs are increasing. Methods In this ecologic time series study, the IMS Health Total Patient Tracker was used to describe nationally projected trends of patients receiving opioids and benzodiazepines in the U.S. outpatient retail setting between January 2002 and December 2014. The IMS Health Data Extract Tool was used to examine trends in the concomitant prescribing of these two medication classes among 177 million individuals receiving opioids during this period. The annual proportion of opioid recipients who were prescribed benzodiazepines concomitantly was calculated and stratified by gender, age, duration of opioid use, immediate-release versus extended-release/long-acting opioids, and benzodiazepine molecule. The proportion of patients with concomitancy receiving opioids and benzodiazepines from the same prescriber was also analyzed. Analyses were conducted from April to June 2015. Results The nationally projected number of patients receiving opioids and benzodiazepines increased by 8% and 31%, respectively, from 2002 to 2014. During this period, the annual proportion of opioid recipients dispensed a benzodiazepine concomitantly increased from 6.8% to 9.6%, which corresponded to a relative increase of 41%. Approximately half of these patients received both prescriptions from the same prescriber on the same day. Concomitancy was more common in patients receiving opioids for ≥90 days, women, and the elderly. Conclusions Concomitant prescribing of opioids and benzodiazepines is increasing and may play a growing role in adverse patient outcomes related to these medications.
Public health authorities have described, with growing alarm, an unprecedented increase in morbidity and mortality associated with use of opioid pain relievers (OPRs). Efforts to address the opioid ...crisis have focused mainly on reducing nonmedical OPR use. Too often overlooked, however, is the need for preventing and treating opioid addiction, which occurs in both medical and nonmedical OPR users. Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid addiction, which in turn has been associated with a rise in overdose deaths and heroin use. A multifaceted public health approach that utilizes primary, secondary, and tertiary opioid addiction prevention strategies is required to effectively reduce opioid-related morbidity and mortality. We describe the scope of this public health crisis, its historical context, contributing factors, and lines of evidence indicating the role of addiction in exacerbating morbidity and mortality, and we provide a framework for interventions to address the epidemic of opioid addiction.
Tramadol has been associated with chronic opioid use and emergency room (ER) visits. However, little is known about trends in prescription tramadol use in the U.S.
Optum's de-identified ...Clinformatics® Data Mart Database was used to assess trends in monthly incident and prevalent tramadol use from 2005 to 2021, stratified by sex and age (18-64 vs. ≥65 years). State-specific trends following scheduling of tramadol as Class IV controlled substance in August 2014 were analyzed with random effects regression models. Demographics, comorbidities, initiation setting, dose, and co-dispensing with other opioids and central nervous system (CNS) agents were assessed in people initiating tramadol, stratified by age and initiation year (2005–2010, 2011–2015, 2016–2021). Analyses were performed in 2023 and 2024.
During 2005–2021, the mean percentage using tramadol in a given month was 0.88% of younger females, 0.55% of younger males, 1.97% of older females, and 1.14% of older males; 5,729,652 initiations were identified. Since 2014, estimated relative yearly decrease was 4% (95% CI 3%; 5%) in use and 5% (95% CI 4%; 5%) in initiation, with variation across states. Primary care percentage of tramadol initiations declined from 49.2% in 2005–2010 to 37.2% in 2016–2021. During 2016–2021, co-dispensing with other CNS agents occurred in 37.8% of younger and 32.1% of older adults initiating tramadol.
Tramadol use was higher in females and older adults, exhibited heterogeneous trends across states, and shifted from primary care to ER and specialist settings over time. Co-dispensing with other CNS agents was common and warrants further monitoring.
During the COVID-19 pandemic, access to in-person care was limited, and regulations requiring in-person dispensing of mifepristone for medical abortions were relaxed. The effect of the pandemic and ...accompanying regulatory changes on abortion use is unknown.
To estimate changes in the incidence rate of induced medical and procedural abortions.
Serial cross-sectional study with interrupted time-series analyses.
Commercially insured persons in the United States.
Reproductive-aged women.
Onset of the COVID-19 pandemic in March 2020 and subsequent regulatory changes affecting the in-person dispensing requirement for mifepristone.
Monthly age-adjusted incidence rates of medical and procedural abortions were measured among women aged 15 to 44 years from January 2018 to June 2022. Medical abortions were classified as in-person or telehealth. Linear segmented time-series regression was used to calculate changes in abortion rates after March 2020.
In January 2018, the estimated age-adjusted monthly incidence rate of abortions was 151 per million women (95% CI, 142 to 161 per million women), with equal rates of medical and procedural abortions. After March 2020, there was an immediate 14% decrease in the monthly incidence rate of abortions (21 per million women CI, 7 to 35 per million women;
= 0.004), driven by a 31% decline in procedural abortions (22 per million women CI, 16 to 28 per million women;
< 0.001). Fewer than 4% of medical abortions each month were administered via telehealth.
Only abortions reimbursed by commercial insurance were measured.
The incidence rate of procedural abortions declined during the COVID-19 pandemic, and this lower rate persisted after other elective procedures rebounded to prepandemic rates. Despite removal of the in-person dispensing requirement for mifepristone, the use of telehealth for insurance-covered medical abortions remained rare. Amid increasing state restrictions, commercial insurers have the opportunity to increase access to abortion care, particularly via telehealth.
Health Resources and Services Administration.
Multiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported ...outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement.
Fifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1 month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. Acute toxicity was documented per RTOG criteria.
Median follow up time was 20 (range 4-44) months. Median PSA at time of diagnosis was 7.4 (2.7-19.5) ng/ml. Eighteen men received 6 months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9 ng/mL at 20 months; 0.08 and 1.32 ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6 ± 4 mm at the prostate midgland. No grade ≥ 3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1 month and in 12% of men at 1 year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4 weeks after SBRT. All GI symptoms were resolving by the 1 month post-treatment assessment and no acute or late rectal toxicity was reported > 1 month after treatment.
Periprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.
The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the ...USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 11% with the EMA, seven of 16 44% with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.
Glucagon-like peptide-1 receptor agonists are effective for treating obesity, but the high cost of these medications endangers the financial viability of our health care system. To ensure that these ...drugs are available to Medicare beneficiaries, pharmaceutical manufacturers must lower their prices.
We aim to test the hypothesis that neurovascular bundle (NVB) displacement by rectal hydrogel spacer combined with NVB delineation as an organ at risk (OAR) is a feasible method for NVB-sparing ...stereotactic body radiotherapy.
Thirty-five men with low- and intermediate-risk prostate cancer who underwent rectal hydrogel spacer placement and pre-, post-spacer prostate MRI studies were treated with prostate SBRT (36.25 Gy in five fractions). A prostate radiologist contoured the NVB on both the pre- and post-spacer T2W MRI sequences that were then registered to the CT simulation scan for NVB-sparing radiation treatment planning. Three SBRT treatment plans were developed for each patient: (1) no NVB sparing, (2) NVB-sparing using pre-spacer MRI, and (3) NVB-sparing using post-spacer MRI. NVB dose constraints include maximum dose 36.25 Gy (100%), V34.4 Gy (95% of dose) <60%, V32Gy <70%, V28Gy <90%.
Rectal hydrogel spacer placement shifted NVB contours an average of 3.1 ± 3.4 mm away from the prostate, resulting in a 10% decrease in NVB V34.4 Gy in non-NVB-sparing plans (
< 0.01). NVB-sparing treatment planning reduced the NVB V34.4 by 16% without the spacer (
< 0.01) and 25% with spacer (
< 0.001). NVB-sparing did not compromise PTV coverage and OAR endpoints.
NVB-sparing SBRT with rectal hydrogel spacer significantly reduces the volume of NVB treated with high-dose radiation. Rectal spacer contributes to this effect through a dosimetrically meaningful displacement of the NVB that may significantly reduce RiED. These results suggest that NVB-sparing SBRT warrants further clinical evaluation.
This is a feasibility study showing that the periprostatic NVBs can be spared high doses of radiation during prostate SBRT using a hydrogel spacer and nerve-sparing treatment planning.
Despite representing 30% to 40% of newly diagnosed cases of adult non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL) rarely presents (1) in the leukemic phase (2) with dysregulation of the ...TP53 tumor suppressor gene and (3) an elevated serum lactic acid level. In this case report and literature review, we highlight this unfortunate triad of poor prognostic features associated with an aggressive and fatal clinical course in a 53-year-old man with recrudescent DLBCL. A leukemic presentation of de novo or relapsed DLBCL is rare and may be related to differential expressions of adhesion molecules on cell surfaces. In addition, TP53 gene mutations are present in approximately 20% to 25% of DLBCL cases and foreshadow worse clinical outcomes. Finally, an elevated serum lactic acid level in DLBCL that is not clearly associated with sepsis syndrome is a poor prognostic factor for survival and manifests as type B lactic acidosis through the Warburg effect.
Transitional care management (TCM) and chronic care management (CCM) fee-for-service billing codes can serve as bridges to help organizations build care management capabilities and effectively ...transition from volume- to value-based care. TCM codes encourage providers to build capabilities for managing hospital discharge transitions. CCM codes encourage physician and nonphysician staff to build capabilities for longitudinally managing patients with multiple chronic conditions. Implementation challenges include achieving return on investment in health information technology and securing stakeholder commitment and engagement. Nonetheless, policy makers have reinforced their commitment to these codes, offering an encouraging signal for organizations seeking more gradual ways to build competencies and bridge toward value-based payment and care delivery.
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