A cohort of patients in New York State with an alcohol use disorder and subsequent treatment information - A merging of two administrative data sources.

OBJECTIVE: Despite the high prevalence of alcohol use disorder (AUD) in the United States, limited research is focused on the associations among AUD, pain, and opioids/benzodiazepine use. In addition, little is known regarding individuals with a history of AUD and their potential risk for pain diagnoses, pain prescriptions, and subsequent misuse. Moreover, the potential risk of pain diagnoses, prescriptions, and subsequent misuse among individuals with a history of AUD is not well known. The objective was to develop a tailored dataset by linking data from 2 New York State (NYS) administrative databases to investigate a series of hypotheses related to AUD and painful medical disorders. METHODS: Data from the NYS Office of Addiction Services and Supports (OASAS) Client Data System (CDS) and Medicaid claims data from the NYS Department of Health Medicaid Data Warehouse (MDW) were merged using a stepwise deterministic method. Multiple patient-level identifier combinations were applied to create linkage rules. We included patients aged 18 and older from the OASAS CDS who initially entered treatment with a primary substance use of alcohol and no use of opioids between January 1, 2003, and September 23, 2019. This cohort was then linked to corresponding Medicaid claims. RESULTS: A total of 177,685 individuals with a primary AUD problem and no opioid use history were included in the dataset. Of these, 37,346 (21.0%) patients had an OUD diagnosis, and 3,365 (1.9%) patients experienced an opioid overdose. There were 121,865 (68.6%) patients found to have a pain condition. CONCLUSION: The integrated database allows researchers to examine the associations among AUD, pain, and opioids/benzodiazepine use, and propose hypotheses to improve outcomes for at-risk patients. The findings of this study can contribute to the development of a prognostic prediction model and the analysis of longitudinal outcomes to improve the care of patients with AUD.

Readmissions and costs among younger and older adults for targeted conditions during the enactment of the hospital readmission reduction program.

BACKGROUND: The Hospital Readmissions Reduction Program (HRRP) was introduced to reduce readmission rates among Medicare beneficiaries, however little is known about readmissions and costs for HRRP-targeted conditions in younger populations. The primary objective of this study was to examine readmission trends and costs for targeted conditions during policy implementation among younger and older adults in the U.S. METHODS: We analyzed the Nationwide Readmission Database from January 2010 to September 2015 in younger (18-64 years) and older (≥65 years) patients with acute myocardial infarction (AMI), heart failure (HF), pneumonia, and acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Pre- and post-HRRP periods were defined based on implementation of the policy for each condition. Readmission rates were evaluated using an interrupted time series with difference-in-difference analyses and hospital cost differences between early and late readmissions (≤30 vs. > 30 days) were evaluated using generalized linear models. RESULTS: Overall, this study included 16,884,612 hospitalizations with 3,337,266 readmissions among all age groups and 5,977,177 hospitalizations with 1,104,940 readmissions in those aged 18-64 years. Readmission rates decreased in all conditions. In the HRRP announcement period, readmissions declined significantly for those aged 40-64 years for AMI (p < 0.0001) and HF (p = 0.003). Readmissions decreased significantly in the post-HRRP period for those aged 40-64 years at a slower rate for AMI (p = 0.003) and HF (p = 0.05). Readmission rates among younger patients (18-64 years) varied within all four targeted conditions in HRRP announcement and post-HRRP periods. Adjusted models showed a significantly higher readmission cost in those readmitted within 30 days among younger and older populations for AMI (p < 0.0001), HF (p < 0.0001), pneumonia (p < 0.0001), and AECOPD (p < 0.0001). CONCLUSION: Readmissions for targeted conditions decreased in the U.S. during the enactment of the HRRP policy and younger age groups (< 65 years) not targeted by the policy saw a mixed effect. Healthcare expenditures in younger and older populations were significantly higher for early readmissions with all targeted conditions. Further research is necessary evaluating total healthcare utilization including emergency department visits, observation units, and hospital readmissions in order to better understand the extent of the HRRP on U.S. healthcare.

Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals.

OBJECTIVE: Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine (Austedo, Teva Pharmaceutical Industries, Ltd) is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools. DATA SOURCES: A search of the MEDLINE (1946 to present) database was undertaken using the Ovid interface. The search was conducted using the heading deuterium and then limited to Administration & Dosage, Adverse Effects, Pharmacokinetics, Pharmacology, Poisoning, Therapeutic Use, and Toxicity. STUDY SELECTION AND DATA EXTRACTION: All articles were reviewed and those with human information were included. Review articles were likewise interrogated for additional published human data. CONCLUSIONS: Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.

High-risk use of prescription opioids among patients treated for alcohol problems in New York State. A repeated cross-sectional study, 2005-2018.

Background: Patients with alcohol use disorder (AUD) and high-risk opioid use are at risk of serious complications. The purpose of this study was to estimate the prevalence of and factors associated with high-risk opioid use in patients with an alcohol use problem from 2005 to 2018. Methods: This repeated cross-sectional study analyzed data from first admissions for alcohol treatment (2005-2018) to the NYS Office of Addiction Services and Supports merged with Medicaid Claims Data. High-risk opioid use was defined as opioid dose ≥50 morphine mg equivalents (MME) per day; opioid prescriptions overlapping ≥7 days; opioids for chronic pain >90 days or opioids for acute pain >7 days. Results: Patients receiving ≥50 MME increased from 690 to 3226 from 2005 to 2010; then decreased to 2330 in 2018. From 2005-2011, patients with opioid prescriptions overlapping ≥7 days increased from 226 to 1594 then decreased to 892 in 2018. From 2005-2010, opioid use >7 days for acute pain increased from 133 to 970 and plateaued after 2010. From 2005-2018, patients who received opioids >90 days for chronic pain trended from 186 to 1655. White patients, females, age 36-55, patients with chronic and acute pain diagnoses had the highest rates of high-risk use. Conclusions: The prevalence of high-risk opioid use in patients with alcohol use problems increased from 2005 to 2011, and generally decreased after 2010. However, prevalence of opioids >90 days for chronic pain trended up from 2005 to 2018. High-risk opioid use among patients with AUD emphasizes the need to develop interventional strategies to improve patient care.

Can machine learning predict pharmacotherapy outcomes? An application study in osteoporosis.

BACKGROUND AND OBJECTIVE: The specific aim of this study is to develop machine learning models as a clinical approach for personalized treatment of osteoporosis. The model performance on outcome prediction was compared between four machine learning algorithms. METHODS: Retrospective, electronic clinical data for patients with suspected or confirmed osteoporosis treated at Wan Fang Hospital between 2011 to 2018 were used as inputs for building the following predictive machine learning models,i.e., artificial neural network (ANN), random forest (RF), support vector machine (SVM) and logistic regression (LR) models. The predicted outcome was defined as an increase/decrease in T-score after treatment. A genetic algorithm was employed to select relevant variables as input features for each model; the leave-one-out method was applied for model building and internal validation. The model with best performance was selected by a separate set of testing. Area under the receiver operating characteristic curve, accuracy, precision, sensitivity and F1 score were calculated to evaluate model performance. Main analysis for all the patients with subclinical or confirmed osteoporosis and subgroup analysis for the patients with confirmed osteoporosis (T score < -2.5) were carried out in this study. RESULTS: A genetic algorithm was employed to select 12 to 18 features from all 33 variables for the four models. No difference was found in accuracy (ANN, 71.7%; LR, 70.0%; RF, 75.0%; SVM, 66.7%), precision (ANN, 80.0%; LR, 59.3%; RF, 70.0%; SVM, 63.6%), and AUC (ANN, 0.709; LR, 0.731; RF, 0.719; SVM, 0.702) among the ANN, LR, RF and SVM models. Main analysis in performance revealed significant recall in the LR model, as compared to ANN and SVM model; while subgroup revealed significant recall in ANN model, compared to LR and SVM model. CONCLUSIONS: Machine learning-based models hold potential in forecasting the outcomes of treatment for osteoporosis via early initiation of first-line therapy for patients with subclinical disease; or a switch to second-line treatment for patients with a high risk of impending treatment failure. This convenient approach can assist clinicians in adjusting treatment tailored to individual patient for prevention of disease progression or ineffective therapy.

Accessibility of postgraduate training program information to graduates from US doctor of pharmacy programs holding F-1 visas.

PURPOSE: To evaluate information provided by residency and fellowship programs to graduates of Accreditation Council for Pharmacy Education-accredited doctor of pharmacy programs holding F-1 visas who are seeking postgraduate training opportunities. METHODS: A 2-phase review of all US-based postgraduate year 1 (PGY1) residency and fellowship programs was conducted. In phase 1, program eligibility criteria were reviewed from the residency and fellowship directories published by the American Society of Health-System Pharmacists (ASHP) and American College of Clinical Pharmacy (ACCP). In phase 2, the postgraduate programs' official websites were reviewed for additional information. Each program was evaluated to determine the eligibility of international students with F-1 visa or Optional Practical Training (OPT) status, visa sponsorship and work authorization opportunities, and citizenship requirements. Programs were classified as eligible or noneligible to international students or as not providing sufficient information. Descriptive statistics were used to summarize the data. RESULTS: A total of 1,455 ASHP PGY1 programs and 69 fellowship programs were included in our analysis. In phase 1, there were 3 eligible programs accepting applicants with F-1/OPT status and 377 noneligible programs. In phase 2, there were 10 eligible programs accepting applicants with F-1/OPT status or providing H-1B sponsorship and 410 noneligible programs. Over 70% of programs (phase 1, n = 1,075; phase 2, n = 1,035) were classified as providing no information. None of the fellowship programs were classified as eligible in our review. CONCLUSION: Most residency and fellowship programs did not provide clear eligibility criteria for students with F-1/OPT status. Only a few programs clearly stated that they would accept applicants with F-1/OPT status or provide visa sponsorship to graduates holding F-1 visas.

Pharmacokinetic drug interactions of integrase strand transfer inhibitors.

The integrase strand transfer inhibitor (INSTI)-containing regimens are currently considered as the first-line treatment of human immunodeficiency virus (HIV) infection. Although possessing a common mechanism of action to inhibit HIV integrase irreversibly to stop HIV replication cycle, the INSTIs, including raltegravir, elvitegravir, dolutegravir, and bictegravir, differ in pharmacokinetic characteristics. While raltegravir undergoes biotransformation by the UDP-glucuronosyltransferases (UGTs), elvitegravir is primarily metabolized by cytochrome P450 (CYP) 3A4 and co-formulated with cobicistat to increase its plasma exposure. The metabolism pathways of dolutegravir and bictegravir are similar, both including CYP3A and UGT1A1, and both agents are substrates to different drug transporters. Because of their differences in metabolism, INSTIs interact with other medications differently through CYP enzymes and transporters as inducers or inhibitors. These drug interactions may become an important consideration in the long-term clinical use because the life expectancy of people with HIV (PWH) approaches to that of the general population. Also, common geriatric challenges such as multimorbidity and polypharmacy have been increasingly recognized in PWH. This review provides a summary of pharmacokinetic interactions with INSTIs and future perspectives in implications of INSTI drug interactions.

The economic impact of 18FDG positron emission tomography in the surgical management of colorectal cancer with hepatic metastases.

BACKGROUND: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is recognized as a powerful tool in the management of patients with recurrent and/or metastatic colorectal cancer. The aim of this was was to analyze costs from the payer's perspective, of adding FDG-PET to a computed tomography (CT) scan preoperatively in colorectal cancer patients with resectable hepatic metastases. METHODS: CT with and without FDG-PET were compared among patients with colorectal cancer in staging for surgical resection of hepatic metastases. Outcomes included uncomplicated surgery, complicated surgery, or death. Extrahepatic disease occurrence rates and diagnostic accuracy of CT and FDG-PET were obtained from published sources. Complication rates and costs for CT, FDG-PET, and surgical procedures were obtained from Healthcare Finance Administration data. RESULTS: The average expected surgical cost per patient when FDG-PET was used to determine the presence of extrahepatic disease was 16,278 dollars compared to 21,547 dollars for conventional management-a net savings of 5,269 dollars. CONCLUSIONS: Integration of FDG-PET into the presurgical evaluation of patients with hepatic metastases could substantially reduce overall costs and patients' morbidity. This substantial net saving results from the unique ability of FDG-PET in excluding patients with extrahepatic disease, and avoiding unnecessary surgical expenses.

Treatment of headache in the elderly.

OPINION STATEMENT: Most primary headaches in the elderly are similar to those in younger patients (tension, migraine, and cluster), but there are some differences, such as late-life migraine accompaniments and hypnic headaches. Although migraine in younger persons usually presents with headache, migraine in older persons may initially appear with visual or sensory phenomena, instead of headache ("migraine accompaniments"). Hypnic headaches awaken patients from sleep, are short-lived, and occur only in the elderly. The probability of secondary headache increases steadily with age. Secondary headaches include those associated with temporal arteritis, trigeminal neuralgia, sleep apnea, post- herpetic neuralgia, cervical spondylosis, subarachnoid hemorrhage, intracerebral hemorrhage, intracranial neoplasm, and post-concussive syndrome. Certain rescue treatments for migraine headache in younger individuals (triptans or dihydroergotamine, for example) should not be used in elderly patients because of the risk of coronary artery disease. Naproxen and hydroxyzine are commonly used oral rescue therapies for older adults who have migraine or tension headaches. Intravenous magnesium, valproic acid, and metoclopramide are all effective rescue therapies for severe headaches in the emergency room setting. Some effective prophylactic agents for migraine in younger patients (amitriptyline and doxepin) are not usually recommended for older individuals because of the risks of cognitive impairment, urinary retention, and cardiac arrhythmia. For these reasons, the recommended oral preventive agents for migraine in older adults include divalproex sodium, topiramate, metoprolol, and propranolol. Oral agents that can prevent hypnic headaches include caffeine and lithium. Cough headaches respond to indomethacin or acetazolamide.

Tobacco sales in pharmacies: a survey of attitudes, knowledge and beliefs of pharmacists employed in student experiential and other worksites in Western New York.

BACKGROUND: Pharmacies are venues in which patients seek out products and professional advice in order to improve overall health. However, many pharmacies in the United States continue to sell tobacco products, which are widely known to cause detrimental health effects. This conflict presents a challenge to pharmacists, who are becoming increasingly more involved in patient health promotion activities. This study sought to assess Western New York (WNY) area pharmacists' opinions about the sale of tobacco products in pharmacies, and pharmacists' opinions on their role in patient smoking cessation. METHODS: Participants responded to two parallel surveys; a web-based survey was completed by 148 university-affiliated pharmacist preceptors via a list based sample, and a mail-based survey was completed by the supervising pharmacist in 120 area pharmacies via a list-based sample. The combined response rate for both surveys was 31%. Univariate and bivariate analyses were performed to determine any significant differences between the preceptor and supervising pharmacist survey groups. RESULTS: Over 75% of respondents support legislation banning the sale of tobacco products in pharmacies. Over 86% of respondents would prefer to work in a pharmacy that does not sell tobacco products. Differences between preceptor and supervising pharmacist groups were observed. Action regarding counseling patients was uncommon among both groups. CONCLUSIONS: Pharmacists support initiatives that increase their role in cessation counseling and initiatives that restrict the sale of tobacco products in pharmacies. These data could have important implications for communities and pharmacy practice.

Preparing pharmacy graduates for traditional and emerging career opportunities.

Educational programs in pharmacy must focus on educating pharmacists of the future who are prepared to serve as competent and confident health care "providers" whose "practice" can occur in any number of current and future settings; and whose expertise is essential to an interprofessional health care team. Graduates must be able to incorporate a scholarly approach to their practice in identifying patient care problems; practicing in an evidence-based manner; and ensuring safe, effective, and appropriate use of medications. It is time for colleges and schools of pharmacy to implement contemporary teaching and assessment strategies that facilitate effective and efficient student learning that is focused at the graduate professional level, to evolve the content around which the curriculum is organized, and clearly articulate the abilities graduates must have to function effectively in the myriad professional roles in which they may find themselves.

Transcranial Doppler measurements in migraine and nitroglycerin headache.

The objective of this study was to examine the cerebral circulation during spontaneous migraine attacks and to compare changes to an experimental headache model induced by nitroglycerin (NTG) infusion. This prospective study was carried out in a tertiary care hospital on migraineurs with or without aura. Healthy volunteers served as controls. There were no interventions. Flow velocity (FV) and pulsatility index (PI) were measured in migraineurs between and during headache attacks. In controls, FV and PI of the middle cerebral arteries were performed at baseline and after each IV infusion of 0.125, 0.25 and 0.5 microg/kg/min of NTG. In migraineurs, a significant increase in the mean flow velocity (MFV) in the left vertebral artery (VA) and the PI of the right VA during spontaneous migraine headache was found. In controls, all FV significantly decreased after infusion of NTG. The NTG model produces expected and substantially different vascular effects than those seen with spontaneous migraine headache.

Transcranial Doppler: an introduction for primary care physicians.

Transcranial Doppler (TCD) is a diagnostic tool that can be used at bedside to assess the cerebral vasculature noninvasively. It is inexpensive, safe, and reliable when compared with other techniques. It can be repeated multiple times and can be used for continuous monitoring if needed. Screening of children with sickle cell disease to assess and prevent ischemic strokes and monitoring for vasospasm after subarachnoid hemorrhage are well established, evidenced based utilizations of TCD. It is useful for the evaluation of occlusive intracranial vascular lesions with many emerging indications in the management of ischemic stroke. TCD with micro-bubble enhancement has comparable sensitivity to transesophageal echocardiogram in detecting right-to-left atrial cardiac shunts. TCD is underused as a clinical tool despite well established indications. The pressure to contain increasing medical cost will likely result in increased utilization of this test in future.

Syncope and head CT scans in the emergency department.

CONTEXT: Patients presenting with syncope to the emergency department (ED) of a community hospital were evaluated. AIM: The objective of this study is to examine the use and results of head computerized tomography (CT) scans in patients presenting with syncope to the ED of a community hospital. SETTINGS AND DESIGN: A retrospective chart review of patients presenting with syncope to the emergency room was conducted. METHODS AND MATERIALS: We reviewed the charts of patients who presented to the ED over a 6-month period with syncope. When performed, head CT scan findings were noted, and their relationship to the clinical presentation was examined. RESULTS: One hundred twenty-eight patients were identified. Forty-four patients had their head CT scans performed. In 1 patient, the CT scan showed evidence of infarction in the posterior circulation. In 19 patients, the head CT scan was normal. Twenty-four patients had abnormal findings unrelated to the ED presentation. CONCLUSIONS: Head CT scans were commonly used in our series of syncope patients. Abnormal findings pertinent to the syncope were observed in only 1 patient. A prospective study examining yield in a larger series of patients may help define the utility of this neuroimaging modality in syncope.

Interaction of colony-stimulating factors and fluorodeoxyglucose f(18) positron emission tomography.

OBJECTIVE: To evaluate reports of altered diagnostic images with fluorodeoxyglucose F(18) (FDG) positron emission tomography (PET) after treatment with colony-stimulating factors (CSFs). DATA SOURCES: Literature was identified by a MEDLINE search (1966-December 2001). Key search terms included granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, fluorodeoxyglucose, and emission-computed tomography. English language literature was reviewed. DATA SYNTHESIS: Reports have suggested altered FDG PET images following CSF treatment. Studies that assessed the effect of CSF administration on FDG PET imaging of the bone and bone marrow were reviewed. CONCLUSIONS: Administration of CSFs may interfere with accurate FDG PET imaging. Separating FDG PET imaging from CSF therapy by >/=5 days may diminish this interference.

Compounded versus proprietary sincalide for evaluation of gallbladder ejection fraction.

OBJECTIVE: To report a comparison of compounded and proprietary sincalide in the evaluation of gallbladder ejection fraction during hepatobiliary scintigraphy. CASE SUMMARIES: Two patients were referred to nuclear medicine with symptoms consistent with hepatobiliary dysfunction. Both underwent hepatobiliary scintigraphy to evaluate anatomic and physiologic tract patency of the hepatobiliary system. Compounded sincalide, an adjuvant pharmaceutical used to evaluate gallbladder ejection fraction, was infused during hepatobiliary scintigraphy, and gallbladder ejection fractions were 11% and 24%, respectively. Hepatobiliary scintigraphy was repeated on both patients 72 hours later with proprietary sincalide used as the adjuvant pharmaceutical. The gallbladder ejection fractions were 32% and 72%, respectively. DISCUSSION: The use of sincalide to evaluate gallbladder ejection fraction in hepatobiliary scintigraphy is widely accepted in the surgical and nuclear medicine community. In late 2001, the sole manufacturer of sincalide announced indefinite unavailability of the product. Following the announcement, several compounding pharmacies began selling extemporaneously compounded sincalide as a replacement. Use of the compounded product has assumed therapeutic equivalence. CONCLUSIONS: Significant differences in gallbladder ejection fraction between compounded sincalide and sincalide in our patients are likely due to the intrinsic variability in response to sincalide. Clinicians should be aware of this variability, as well as the potential effect of concomitant medications.

Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 12-week interim analysis.

Observations on the neurochemistry of dementia with Lewy bodies (DLB) have suggested that cholinesterase inhibitors (ChEIs) might be beneficial in treating some clinical symptoms of DLB. A 24-week, multicenter open-label study was designed to assess the safety and efficacy of the ChEI galantamine in patients with DLB, and an interim analysis of results was performed at 12 weeks. Efficacy analyses were performed on data from 25 patients. Scores on the Neuropsychiatric Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks (marginally significant, p = 0.061). NPI-12 scores decreased by half in 12 of the 25 patients. Highly significant improvement was observed in scores on the NPI-4 subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores on the Clinician's Global Impression of Change (CGIC) improved by 0.95 points (significant, p = 0.02). Improvements also were found in secondary efficacy variables, including cognitive, functional, activities of daily living, sleep and confusion assessments. Motor scores, as measured by the UPDRS motor subscale, showed mild improvement, which demonstrates that galantamine has no adverse effect on parkinsonian symptoms. Adverse events generally were transient and of mild-to-moderate intensity. Two of the 25 patients discontinued galantamine because of nausea and anorexia. One serious adverse event was recorded, but it was judged to be unrelated to the study medication.