Concurrent Medication Use Research Articles

Psilocybin for depression: Considerations for clinical trial design

Background and aims Given the enormous global burden of depressive illness, there is an urgent need to develop novel and more effective treatments for major depressive disorder (MDD). Recent findings have suggested that psychedelic drugs may have a role in the treatment of depressive symptoms, and a number of groups are in the process of developing protocols to study this question systematically. Given the subjective quality of both the psychedelic experience and depressive symptomatology, great care must be taken when designing a protocol to study the clinical efficacy of psychedelic drugs. This study will discuss many factors to consider when designing a clinical trial of psilocybin for MDD. Methods We provide a thorough review of pertinent research into antidepressant clinical trial methodology and review practical considerations that are relevant to the study of psychedelic-assisted treatment for depression. Results We discuss participant selection (including diagnostic accuracy, exclusion criteria, characteristics of the depressive episode, and the use of concurrent medications), study interventions (including dosing regimens, placebo selection, non-pharmacological components of treatment, and the importance of blinding), trial duration, outcome measures, and safety considerations. Conclusions Careful and transparent study design and data analysis will maximize the likelihood of generating meaningful, reproducible results, and identifying a treatment-specific effect. Meeting the highest standards for contemporary trial design may also broaden the acceptance of psychedelic research in the scientific community at large.

Systemic medications and cortical cataract: the Singapore Epidemiology of Eye Diseases Study

Background/aimsTo evaluate the association between systemic medications and cortical cataract prevalence in an Asian population.MethodsThe Singapore Epidemiology of Eye Diseases Study recruited 10 033 Chinese, Malay and Indian residents aged...

A Retrospective Examination of Symptom Improvements in Primary Care Patients Receiving Behavior Therapy With and Without Concurrent Pharmacotherapy.

Primary care providers are the biggest prescribers of psychopharmacological medications. In this non-randomized retrospective examination, we asked whether primary care patients receiving behavioral health interventions with and without concurrent pharmacological treatments showed differential symptom improvement. Participants (79.4% women, 61.5% Hispanic, M age = 41.68, SD = 13.50) were 431 primary care patients referred to behavioral health with a primary concern of depression at one of three federally qualified health centers. Thirty-three percent of patients initiated or had an increase in pharmacotherapy concurrently with behavioral therapy; 26.9% had no change in medication during the episode of care, and 39.7% had no concurrent psychotropic medication prescribed during the episode of care. One-way analyses of variance revealed patients in the no medication group had higher global functioning, as measured by Global Assessment of Functioning (GAF) scores, than patients who were taking medication, or who initated or had an increase in medication. There was a significant main effect of time, where patients had significantly higher GAF scores during their last session in comparison to the first session. All three patient groups experienced comparable improvements in GAF scores, but patients in the initiated/increased medication group were significantly more likely to terminate behavioral health treatment prematurely. Results suggest primary care patients experience improvements in functioning across an episode of behavioral health care, even without concurrent psychotropic medication use.

Temporal associations between medication adherence for patients with schizophrenia and opioid dependence: A 17-year Canadian Cohort Study

The current study investigated whether a previously reported beneficial effect of methadone maintenance therapy (MMT) on antiretroviral adherence is also present in relation to antipsychotic treatment for schizophrenia. Administrative data were linked over a 17-year period for 1996 people who were dually diagnosed with schizophrenia and opioid dependence and, as an indicator of further marginalization, experienced at least one episode of correctional supervision in British Columbia. Adherence was estimated using the medication possession ratio (MPR ≥ 0.80), calculated in each 120-day period beginning with the first date of concurrent use of MMT and antipsychotic medication. Generalized Estimating Equations were used to estimate the association between independent and dependent variables. The probability of antipsychotic adherence doubled in periods that were preceded by a period of MMT adherence (AOR: P: 2.07; 95% CI: 1.90–2.26). Subgroup and sensitivity analyses yielded results similar to those derived through the primary analysis, examining: conviction history; length of follow-up; initiation of MMT prior to antipsychotic induction; excluding participants who died during the study period; and restricted to participants who received methadone exclusively as part of a MMT program. Despite a strong temporal association between MMT and antipsychotic adherence, overall MPRs for both prescriptions remained <0.50 throughout the study period. Antipsychotic adherence was more than twice as likely following periods of adherence to MMT among dually-diagnosed patients. Research is needed to identify the conditions responsible for MMT adherence, and to further clarify the relationship between opioid agonist treatment and antipsychotic pharmacotherapy in this vulnerable and under-studied population.

SUN-402 Iatrogenic Cushing's Syndrome following Epidural Steroid Injections in an HIV-Infected Patient on Treatment with Genvoya

Introduction: We report the first known case of iatrogenic Cushing's syndrome in a patient with concomitant use of epidural triamcinolone injections and Genvoya therapy for HIV. Clinical Case: A 76-year-old female with HIV and diabetes presented with two months of fatigue, 6lb weight loss, and uncontrolled hyperglycemia. Her HIV-RNA level was suppressed on Genvoya, a four-drug combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide.1 She had received four 80 mg epidural triamcinolone acetonide injections six months apart for chronic back pain starting 18 months before admission. The most recent injection was one month before presentation. She reported fatigue, depressed mood and difficulty ambulating. Examination was notable for plethoric moon facies, proximal muscle weakness, and episodic hypotension. Endocrine evaluation revealed evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression with a low morning cortisol level of 4.5 mcg/dL (5-25 mcg/dL); repeat testing was undetectable at 0.8 mcg/dL. Response to Cosyntropin stimulation was adequate (cortisol 17.8 mcg/dL at 60 minutes). A urine synthetic glucocorticoid panel showed an elevated triamcinolone acetonide level of 0.69 mcg/dL (cutoff value 0.10, Mayo Medical Labs, MN). We hypothesized that the interaction between Genvoya and triamcinolone led to iatrogenic Cushing's syndrome with suppression of her endogenous HPA axis, via the inhibition of steroid metabolism by Cobicistat, a hepatic CYP3A4 inhibitor. By applying the Naranjo Nomogram for Causality and the Drug Interaction Probability Scale to this interaction, we estimated a score of 5 (probable) and 6 (probable), respectively. Her antiretroviral medication was changed to emtricitabine, tenofovir alafenamide, and dolutegravir. She was started on maintenance hydrocortisone to prevent an adrenal crisis, with immediate improvement in fatigue, muscle weakness, and improved ambulation. A repeat urine glucocorticoid panel, within three days of her HIV regimen being changed, showed a decrease in triamcinolone levels to 0.32 mcg/dL. Conclusion: Cobicistat, a CYP3A4 inhibitor, can potentiate pharmacokinetic drug interactions with the concurrent use of other medications metabolized via this pathway. A literature review revealed a single case report of adrenal insufficiency following triamcinolone injections while on the HIV medication Stribild, which also contains cobiscistat.2 To our knowledge, there are no prior reports of Cushing's syndrome with Genvoya and exogenous steroids. We aim to increase awareness of this potential interaction to avoid adverse effects in patients on Genvoya also receiving corticosteroids.

Parameters associated with efficacy of epidural steroid injections in the management of postherpetic neuralgia: the Mayo Clinic experience.

Purpose: Thirty percent of patients with postherpetic neuralgia (PHN) receiving conservative treatment report unsatisfactory pain relief. Epidural steroid injections (ESIs) are commonly used as a therapeutic intervention in these patients. In this study, we aimed to determine if there are variables that predict the efficacy of ESI in patients with PHN.Patients and methods: We retrospectively identified patients seen at Mayo Clinic who had PHN and received ESI. From their medical records, we abstracted the demographic variables, concurrent medication use, anatomic approach and medication for ESI, and degree of pain relief at 2 and 12 weeks' postintervention.Results: None of the studied variables were significantly associated with efficacy of ESI in patients with PHN. PHN that began <11 months before treatment was predictive of a response to ESI at 12 weeks postintervention (positive predictive value, 55%). Patients who reported poor ESI efficacy 2 weeks after the intervention had a 94% chance of still having pain at 12 weeks.Conclusion: For this cohort of patients with PHN being treated with ESI, no demographic characteristics, concurrently used medications, or type of ESI were associated with ESI treatment efficacy at 2 or 12 weeks after the intervention.

Optimizing Management of Medically Responsive Epilepsy.

This article reviews the management of patients with medically responsive epilepsy, including discussion of factors that may lead to transient breakthrough seizures and patient and physician strategies to maintain freedom from seizures. Imperfect adherence, unanticipated changes in ongoing medical therapy, inadvertent use of proconvulsants or concurrent medications that alter epilepsy medication kinetics, and a variety of seizure precipitants such as stress or sleep deprivation may alter long-term seizure control. The majority of patients with epilepsy are medically responsive. Many potential factors may lead to breakthrough seizures in these patients. Identification of these factors, patient education, and use of self-management techniques including mindfulness therapy and cognitive-behavioral therapy may play a role in protecting patients with epilepsy against breakthrough seizures.

Impact of prior and concurrent medication on exacerbation risk with long-acting bronchodilators in chronic obstructive pulmonary disease: a post hoc analysis

BackgroundSymptomatic patients with chronic obstructive pulmonary disease (COPD) and low exacerbation risk still have disease instability, which can be improved with better bronchodilation. We evaluated two long-acting bronchodilators individually and in combination on reducing exacerbation risk and the potential impact of concurrent medication in these patients.MethodsIntegrated post hoc intent-to-treat (ITT) analysis of data from two large 24-week, randomized placebo (PBO)-controlled trials (NCT01313637, NCT01313650). Symptomatic patients with moderate-to-very-severe COPD with/without an exacerbation history were randomized (2:3:3:3) to once-daily: PBO, umeclidinium/vilanterol (UMEC/VI 62.5/25 μg [NCT01313650] or 125/25 μg [NCT01313637]), UMEC (62.5 [NCT01313650] or 125 μg [NCT01313637]) or VI (25 μg) via the ELLIPTA inhaler. Medication subgroups were segmented by treatment status at screening: a) maintenance-naïve or on maintenance medications, b) inhaled corticosteroid [ICS]-free or ICS-treated, c) low or high albuterol use based on median run-in use (< 3.6 or ≥ 3.6 puffs/day). Time to first moderate/severe exacerbation (Cox proportional hazard model) and change from baseline in trough forced expiratory volume in 1 s (FEV1; mixed model repeated measures) were analyzed. Safety was also assessed.ResultsOf 3021 patients (ITT population; UMEC/VI: n = 816; UMEC: n = 825; VI: n = 825; PBO: n = 555), 36% had a recent exacerbation history, 33% were maintenance-naïve, 51% were ICS-free. Mean baseline albuterol use was 5.1 puffs/day. In the ITT population, UMEC/VI, UMEC, and VI reduced the risk of a first exacerbation versus PBO by 58, 44, and 39%, respectively (all p < 0.05). UMEC/VI provided significant risk reductions versus PBO in all subgroups. VI had no benefit versus PBO in maintenance-naïve, ICS-free, and low rescue use patients and was significantly less effective than UMEC/VI in these subgroups. UMEC had no significant benefit versus PBO in maintenance-naïve and ICS-free patients. All bronchodilators improved FEV1 versus PBO, and UMEC/VI significantly improved FEV1 versus both monotherapies across all populations studied (p < 0.05). All bronchodilators were similarly well tolerated.ConclusionsResults suggest that UMEC/VI reduces exacerbation risk versus PBO more consistently across medication subgroups than UMEC or VI, particularly in patients with no/low concurrent medication use. Confirmed prospectively, these findings may support first-line use of dual bronchodilation therapy in symptomatic low-risk patients.

Adherence and Concomitant Medication Use among Patients on Warfarin Therapy: Insight from a Large Pharmacy Dispensing Database in Japan.

Warfarin is a drug used for anticoagulation management, with a narrow therapeutic range and multiple drug-drug interactions. Adherence and proper use of concomitant medication are thus fundamental to the efficacy and safety of warfarin therapy. In 2012, we retrospectively analyzed data from three large-scale pharmacy chains in Japan. We included all adults (≥ 20 years old) with at least one record of warfarin dispensation. We examined patient demographic data, adherence as measured by medication possession ratio (MPR), and co-dispensation focusing on the number of concomitant dispensations and concurrent use of medications that increase bleeding risk. Thresholds of underadherence and overadherence were set at <0.9 and >1.1, considering the narrow therapeutic window. We reviewed 443007 warfarin dispensation records of 71340 individuals (median age, 73 years; 62% male). The MPR was 1.0 (interquartile range: 0.96-1.0), and underadherence and overadherence was found in 16.3 and 1.9% of individuals, respectively. The median number of co-dispensed drugs was eight at each pharmacy encounter, which did not differ by age group. Drugs associated with a high bleeding risk were dispensed in 40.0% of encounters and accounted for 16.4% of all co-dispensed drugs. In summary, we found optimal overall adherence, as assessed by MPR, among our Japanese study population, even when defining a strict cut-off value. However, polypharmacy was common in all age groups and medications with a high bleeding risk profile were often co-dispensed with warfarin. Future research addressing how these dispensation patterns affect patient outcome is warranted.

Statins reduce the progression of non-advanced adenomas to colorectal cancer: a postcolonoscopy study in 187 897 patients

Background and aimsPostcolonoscopy colorectal cancer (PCCRC) accounts for up to 9% of all CRCs. Statins have been shown to be associated with a lower CRC risk. We aimed to investigate...

Racial Disparities in Virologic Failure and Tolerability During Firstline HIV Antiretroviral Therapy.

BackgroundRacial/ethnic disparities in HIV outcomes have persisted despite effective antiretroviral therapy. In a study of initial regimens, we found viral suppression varied by race/ethnicity. In this exploratory analysis, we use clinical and socioeconomic data to assess factors associated with virologic failure and adverse events within racial/ethnic groups.MethodsData were from AIDS Clinical Trial Group A5257, a randomized trial of initial regimens with either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir (each combined with tenofovir DF and emtricitabine). We grouped participants by race/ethnicity and then used Cox-proportional hazards regression to examine the impact of demographic, clinical, and socioeconomic factors on the time to virologic suppression and time to adverse event reporting within each racial/ethnic group.ResultsWe analyzed data from 1762 participants: 757 self-reported as non-Hispanic black (NHB), 615 as non-Hispanic white (NHW), and 390 as Hispanic. The proportion with virologic failure was higher for NHB (22%) and Hispanic (17%) participants compared with NHWs (9%). Factors associated with virologic failure were poor adherence and higher baseline HIV RNA level. Prior clinical AIDS diagnosis was associated with virologic failure for NHBs only, and unstable housing and illicit drug use for NHWs only. Factors associated with adverse events were female sex in all groups and concurrent use of medications for comorbidities in NHB and Hispanic participants only.ConclusionsClinical and socioeconomic factors that are associated with virologic failure and tolerability of antiretroviral therapy vary between and within racial and ethnic groups. Further research may shed light into mechanisms leading to disparities and targeted strategies to eliminate those disparities.

Analysis of Factors That Interrupt With INR Control in the First Anticoagulation Clinic Monitoring Jordanian Patients.

Multiple factors such as vitamin K consumption, drug interactions, herbs interactions, disease states, and alcohol intake affect international normalized ratio (INR) values and thus warfarin dosing. These variables have been described in general and for all patients in the literature. In contrast, the factors that affect INR control in a specific population are rarely studied. Being aware of these factors contributes a lot in maintaining an INR control and avoiding the supratherapeutic or subtherapeutic anticoagulation and the associated risks of hemorrhage or thromboembolism. The aim of this study is to recognize the specific population factors in Jordanian patients that interrupt INR control. Such recognition provides clinical pharmacists managing the anti-coagulation clinic (ACC) with necessary tools and predictors of dose adjustment, nontarget INR handling, and points to add on to the educational session. A total of 2788 patients were referred to the first clinical pharmacists managed ACC at Queen Alia Heart Institute—the only official referral hospital for cardiac patients in Jordan—for education and monitoring between November 1, 2013, and November 1, 2016. We evaluated specific population factors that interrupt INR control using a pretested, structured clinical data collection form. The patients were followed up regularly for achieving target INR (TINR). For patients who were not achieving TINR, the possible cause was examined thoroughly by reviewing the patient’s medical file for recent medication intake, comorbidities, and laboratory results. Then the patients or their caregiver were asked direct questions regarding their diet, food supplements, cigarette smoking, shisha smoking, alcohol intake, herbs, and complementary medicine use and compliance, in addition to performing pharmacogenetic testing (polymorphisms of vitamin K–epoxide reductase complex [VKORC1] and cytochrome P450 2C9 [CYP2C9] genes) in special cases. For a total of 2788 patients, 89 488 INR values were included in the study. Of all, 20 365 (22.8%) were non-TINR values, 13 145 (14%) were subtherapeutic, and 7220 (8.1%) were supratherapeutic. All patients included in the study had a non-TINR at least 3 times (n = 65, 2.3%) and as frequent as 50 times (n = 21, 0.8%) during the study period. Non-TINR values ranged from 1 to 11. Serious side effects reported in 7 patients with uncontrolled INR, 6 were bleeding, which required hospitalization (2 upper gastrointestinal [GI] bleeding, 3 nasal bleeding, and 1 eye bleeding), 1 was cerebrovascular accident (CVA thrombolytic). Factors that interrupted INR control in our population, arranged in descending sequence, were concurrent medication use 46.9% (mainly Salicylates and Amiodarone), smoking cigarettes and shisha 17% (represented the most frequent single factor that caused non-TINR in the present study), a nonbalanced dietary vitamin K intake 16.88% caused changes in INR (lower) was related to an increase in the intake of vitamin K-rich food, were noticed to be much more in the spring season in Jordan (end of March and April mainly), herbal supplements 15.02%; Hawthorn (Crataegus, الزعرور) is an herb that lives widely in Jordan, and shockingly we found that it is used very commonly in our ACC patients and corresponded to an elevated INR <8 in 11 patients, and serious bleeding events that required hospitalization in 2 cases), noncompliance 1.49%, comorbid diseases 1%, malabsorption 0.53%, alcohol intake 0.39%, and VKORC1 A/G and CYP2C9 *1*1 genotype 0.15%. The analysis of factors that interrupted with INR control in our patients were both predicted and distinctive; most of these factors were reported previously by other researchers. On the other hand, many of the previously reported factors were not frequently detected in our patients, and the frequency of each of the realized factors was contributed differently to non-TINR in our population. Alarming factors causing non-TINR detected in our study include smoking both cigarettes and shisha, herbal use (Hawthorn and Ginseng), increased intake of vitamin K rich food in the spring season, and concurrent medication use (Salicylates, Amiodarone, Ciprofloxacin, nonsteroidal anti-inflammatory drugs [NSAIDS], Azithromycin, Clarithromycin: although the use of these drugs is mandatory sometimes, it can be replaced by an alternative, eg, antibiotics or monitored closely together with warfarin).

Idiopathic toxic epidermal necrolysis in an adolescent

A 10‐year‐old girl, suspected 2 days prior to have streptococcal pharyngitis, presented with diffuse erythema, tense bullae, Nikolsky‐positive desquamation, as well as ulcerations of her oral and genital mucosa. She denied recent travel, sick contacts, or preceding and concurrent use of medications, including over‐the‐counter and herbal supplements. A comprehensive viral polymerase chain reaction (PCR) panel, Mycoplasma pneumoniae PCR and IgM, streptococcal molecular antigen test, urine culture, blood culture, and rheumatologic serologies were negative. Based on the patient's clinical presentation and biopsy results, she was diagnosed with idiopathic toxic epidermal necrolysis.

Caffeine Sodium Benzoate for Electroconvulsive Therapy Augmentation.

Because of an ongoing manufacturer shortage of injectable caffeine sodium benzoate (CSB), patients at our health system were given CSB compounded in-house to increase seizure response during electroconvulsive therapy (ECT). Therefore, we aimed to evaluate its effectiveness and safety as an ECT augmentation agent. Medical records of patients who received compounded CSB at Virginia Commonwealth University Health System were reviewed to identify adults receiving it as part of an index ECT treatment course between June 2012 and December 2016. The primary outcome was change in electroencephalogram seizure duration from pre-caffeine session to initial caffeine session. Data were also collected on demographics, motor seizure duration, maximum heart rate, mean arterial pressure, and concurrent medication use for these sessions and the last caffeine session. Seven-one patients were included in the study, predominantly white females with a mean age of 58.6 years. The most common indication for ECT was major depressive disorder resistant to pharmacotherapy (71.8%), followed by catatonia associated with another mental disorder (19.7%). Electroencephalogram seizure duration increased by 24.1 seconds on average with first CSB use (P < 0.0001), allowing 24 more patients overall to achieve goal of at least 30 seconds (P < 0.0001). No clinically significant changes in maximum heart rate or mean arterial pressure were observed, nor did any patients require an abortive agent for prolonged seizure. Five patients (7%) discontinued CSB prematurely: 4 related to adverse effects and 1 secondary to ineffectiveness. We confirm results of prior studies of the utility of CSB and add that compounded CSB is effective for ECT augmentation, maintaining effectiveness throughout the index course with minimal safety concerns.

Predictors of polypharmacy among elderly Thais with depressive and anxiety disorders: findings from the DAS study

BackgroundPolypharmacy is a geriatric syndrome defined variously as the use of potentially inappropriate drugs and/or the concurrent use of multiple medications including prescription and over-the-counter drugs. An association has been shown between polypharmacy and physical health, increased morbidity and increased mortality. However, there is little information regarding the association between polypharmacy and physical disease, personality trait and mental health problems in elderly. The aim of this study was to investigate potential predictive psychosocial factors related to polypharmacy in elderly Thai people.MethodsThe study analysed the secondary data from the Depressive Disorders, Anxiety Disorders, Suicide Risk and Associated Factors Among Elderly Thai People Program (DAS Study) which was funded by National Research Council of Thailand and conducted between January 2012 and April 2013. Demographic and baseline clinical characteristics including sex, age, education, living alone or with others, access to health care privilege and monthly income were described. The number of medication, physical diseases and mental health problems (i.e. depression, anxiety, and personality trait of neuroticism) were analyzed using descriptive statistics, chi-square and proportional odds logistic regression.ResultsThe 803 participants consumed an average of 2.13 prescribed medicines daily (SD 1.46, median = 2). The largest group used 3 medications (18.6%). Predictors found to be associated with polypharmacy in the logistic regression model included hypertension (OR = 1.985, 95% CI = 1.420–2.775), anxiety disorder (OR = 4.402, 95% CI = 2.630–7.367), number of diseases (OR = 2.140, 95% CI = 1.874–2.445), depressive disorder (OR = 1.470, 95% CI = 1.080–2.001), diabetes mellitus (OR = 1.864, 95% CI = 1.122–3.098) and dyslipidemia (OR = 0.511, 95%CI = 0.325–0.803).ConclusionsThe prevalence of polypharmacy among Thai elderly was relatively high compared to other related studies. Several aspects should be taken into consideration before starting an additional medication in elderly patients. In addition to the number of physical disease that leads to polypharmacy, general practitioners should be aware of anxiety, depression, and personality trait of neuroticism that may be related to polypharmacy. Early detection for such condition as well as non-pharmacological intervention could be one way to help reduce polypharmacy in the elderly.

Polypharmacy and medication costs at end of life among commercially insured adults age 65 and older with cancer.

65 Background: Polypharmacy, or the concurrent use of multiple medications, may expose patients to drug-drug interactions and excessive costs. There are limited data on polypharmacy for commercially insured older adults, primarily Medicare Advantage patients, that may have better access to medication management services than Medicare fee-for-service patients. We characterized medication use and out-of-pocket (OOP) medication costs in the last month of life among patients age 65+ who did not enroll in hospice to examine medication use in this population. Methods: We linked enrollment and claims records from two regional commercial insurers to Surveillance, Epidemiology, and End Results (SEER) Cancer Surveillance System and Washington State Cancer Registry records for patients diagnosed with a stage IV malignancy in Washington State between January 1, 2007-December 31, 2016. We calculated OOP costs as the difference between allowed and paid claim amounts and adjusted OOP costs (aOOP) for inflation to 2017 dollars. Results: Among 345 patients with medication claims in their last month, 156 (45%) had a chemotherapy claim. Average age was 74 years (range 65-95), 55% (n = 190) were male, and 150 had lung cancer (44%). Patients averaged 7.7 medication claims (range 1-50); 151 (44%) had 1-4, 99 (29%) had 5-9, and 95 (27%) had 10+. Common symptom-related medications were opioids, benzodiazepines, anti-emetics. Chemotherapy was associated with higher odds of 10+ prescriptions (OR 1.38, 95% CI 1.26-1.51). Excluding four patients with aOOP chemotherapy costs &gt; $14,000, average aOOP costs were $101 for chemotherapy claims (range $0-$8957) and $33 for non-chemotherapy claims ($0-$1993). Costs for those in the highest quartile ranged from $320-$8957 for chemotherapy claims and $100-1993 for non-chemotherapy claims. Conclusions: Most subjects had at least five medication claims in their last 30 days. One-quarter had 10+ claims, which was associated with chemotherapy receipt. Hospice enrollment could reduce OOP costs, as hospice provides symptom-related medications. Interventions facilitating hospice enrollment and reducing chemotherapy use may minimize polypharmacy and cost burden for patients and families.

Controversies in Breastfeeding

When addressing the compatibility of breastfeeding with certain maternal conditions, we need to differentiate between “contraindication” and “obstacle.” Failure to distinguish between the two confuses new mothers and their families, and engenders misconceptions about breastfeeding advice by health professionals. Health conditions that may simply impede the initiation and duration of breastfeeding are often wrongly referred to as true contraindications to breastfeed, under the assumption that they might harm the health of the mother and/or that of the nursing infant. Here, we discuss several topics, including breast surgery, prolactinoma, concurrent new pregnancy, hormonal contraception, and use of medications and contrast agents, that continue to raise controversy. While most conditions appear to be compatible with breastfeeding, the major determinants of a woman's final choice of whether to nurse her infant or not are the attitude of health professionals and the state of mind of being an informed mother.

'I take my tablets with the whiskey': A qualitative study of alcohol and medication use in mid to later life.

BackgroundConcurrent alcohol and medication use can result in significant problems especially in mid to later life. Alcohol is often used instead of medication for a number of health-related conditions. This novel qualitative study explored concurrent alcohol and medication use, as well as the use of alcohol for medicinal purposes, in a sample of individuals in mid to later life.MethodsTwenty-four interviews (12 men/12 women, ages 51–90 years) and three focus groups (n = 27, 6 men/21 women, ages 50–95 years) from three branches of Age UK and two services for alcohol problems in North East England.ResultsOlder people in this study often combined alcohol and medication, frequently without discussing this with their family doctor. However, being prescribed medication could act as a motivating factor to stop or reduce alcohol consumption. Participants also used alcohol to self-medicate, to numb pain, aid sleep or cope with stress and anxiety. Some participants used alcohol to deal with depression although alcohol was also reported as a cause of depression. Women in this study reported using alcohol to cope with mental health problems while men were more likely to describe reducing their alcohol consumption as a consequence of being prescribed medication.ConclusionsAs older people often combine alcohol and medication, health professionals such as family doctors, community nurses, and pharmacists should consider older patients’ alcohol consumption prior to prescribing or dispensing medication and should monitor subsequent drinking. In particular, older people should be informed of the dangers of concurrent alcohol and medication use.

Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated Hypotension: A Retrospective Cohort Study.

Tizanidine, a widely used muscle relaxant that can lower blood pressure, is metabolized by the cytochrome P450 1A2 (CYP1A2). We studied 1,626 patients prescribed tizanidine and 5,012 prescribed cyclobenzaprine concurrently with a strong CYP1A2 inhibitor. The primary outcome was severe hypotension, defined as systolic blood pressure (SBP) ≤70mmHg during periods of drug co-exposure. Severe hypotension occurred more often in the tizanidine group (2.03%; n=33) than the cyclobenzaprine group (1.28%; n=64); odds ratio (OR)=1.60; P=0.029. This difference remained statistically significant after adjustment for a log-transformed propensity score that included age, sex, race, Charlson's comorbidity index, and concurrent use of antihypertensive medications (OR=1.57; P=0.049). A sensitivity analysis that defined hypotension as SBP <90mmHg also yielded higher rates of hypotension among patients prescribed tizanidine. In conclusion, CYP1A2 inhibition increases the risk of hypotensive episodes associated with the use of tizanidine in routine clinical practice.

Building interpretable models for polypharmacy prediction in older chronic patients based on drug prescription records.

BackgroundMultimorbidity presents an increasingly common problem in older population, and is tightly related to polypharmacy, i.e., concurrent use of multiple medications by one individual. Detecting polypharmacy from drug prescription records is not only related to multimorbidity, but can also point at incorrect use of medicines. In this work, we build models for predicting polypharmacy from drug prescription records for newly diagnosed chronic patients. We evaluate the models’ performance with a strong focus on interpretability of the results.MethodsA centrally collected nationwide dataset of prescription records was used to perform electronic phenotyping of patients for the following two chronic conditions: type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD). In addition, a hospital discharge dataset was linked to the prescription records. A regularized regression model was built for 11 different experimental scenarios on two datasets, and complexity of the model was controlled with a maximum number of dimensions (MND) parameter. Performance and interpretability of the model were evaluated with AUC, AUPRC, calibration plots, and interpretation by a medical doctor.ResultsFor the CVD model, AUC and AUPRC values of 0.900 (95% [0.898–0.901]) and 0.640 (0.635–0.645) were reached, respectively, while for the T2D model the values were 0.808 (0.803–0.812) and 0.732 (0.725–0.739). Reducing complexity of the model by 65% and 48% for CVD and T2D, resulted in 3% and 4% lower AUC, and 4% and 5% lower AUPRC values, respectively. Calibration plots for our models showed that we can achieve moderate calibration with reducing the models’ complexity without significant loss of predictive performance.DiscussionIn this study, we found that it is possible to use drug prescription data to build a model for polypharmacy prediction in older population. In addition, the study showed that it is possible to find a balance between good performance and interpretability of the model, and achieve acceptable calibration at the same time.