The frequency and nature of clinician identified medication-related rapid response system calls.

Resuscitation. 2019 Oct 11;:

Authors: Levkovich BJ, Bingham G, Orosz J, Cooper DJJ, Kirkpatrick CM, Dooley MJ, Jones DA

Abstract
AIM: The contribution of adverse medication events to clinical deterioration is unknown. This study aimed to determine the frequency and nature of rapid response system (RRS) calls that clinicians perceived were medication-related using RRS quality arm data.
METHODS: Analysis of routine data prospectively collected by clinicians responding to RRS calls in an Australian acute tertiary academic hospital.
RESULTS: Between January 2013 and June 2017, 12,221 adult patients triggered the RRS for 25,906 medical emergency team (MET) and 512 code blue calls. Clinicians identified 433 medication-related RRS calls (1.6%) involving 406 patients (3.3%). These included 418 MET calls (1.3 medication-related MET calls per 1000 admissions) and 15 code blue calls (0.045 medication-related code blue calls per 1000 admissions). Medication-related calls occurred earlier in the admission (p = 0.002) and were more common for patients triggering multiple calls during the same admission (p < 0.001), compared to non-medication-related calls. Medication-related calls most commonly were triggered by low blood pressure (38.3%) and involved cardiovascular (43.0%) and nervous system medications (36.0%). Dose-related toxicity (n = 178) was the most frequent adverse medication event contributing to medication-related calls.
CONCLUSION: One in 30 patients triggering a RRS call experienced medication-related clinical deterioration, most often due to dose related toxicity of cardiovascular system medications. The perceived frequency and potential preventability of this medication-related harm suggest further research is required to increase recognition of medication-related RRS calls by responding clinicians and to reduce the incidence.

PMID: 31610227 [PubMed - as supplied by publisher]

Selection design phase II trial of high dosages of tamoxifen and creatine in amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener. 2019 Oct 14;:1-9

Authors: Babu S, Macklin EA, Jackson KE, Simpson E, Mahoney K, Yu H, Walker J, Simmons Z, David WS, Barkhaus PE, Simionescu L, Dimachkie MM, Pestronk A, Salameh JS, Weiss MD, Brooks BR, Schoenfeld D, Shefner J, Aggarwal S, Cudkowicz ME, Atassi N

Abstract
Objective: To conduct a phase-II trial using a ranking and selection paradigm where multiple treatments are compared with limited sample size and the best is chosen for a subsequent efficacy trial versus placebo. This strategy can find an effective treatment faster than traditional strategy of conducting larger trials against placebo. Methods: Sixty amyotrophic lateral sclerosis (ALS) participants were randomized 1:1:1 to creatine 30 g/day (CRE), tamoxifen 40 mg/day (T40), or tamoxifen 80 mg/day (T80), with matching placebo. The primary outcome was 38-week change in ALS Functional Rating Scale-Revised (ALSFRS-R), analyzed in a repeated-measures ANOVA. Secondary outcomes included slow vital capacity (SVC), quantitative muscle strength, early drug discontinuation (EDD), adverse events (AEs), and survival. Results: CRE participants experienced higher rates of drug-related AEs (82% vs. 43% T40, 47% T80) and EDD (50% vs. 24% T40, 29% T80). T80 participants experienced slower adjusted mean decline in ALSFRS-R in points/month (-0.80 vs. -0.84 T40, -0.85 CRE) and quantitative muscle strength but not in SVC and higher rates of mortality. Conclusion: Efficacy of T80 ranked numerically superior to CRE and T40 with respect to ALSFRS-R decline. Following the selection paradigm, T80 would be chosen to test against placebo. The approach was not designed to distinguish among treatments that are nearly equally effective or ineffective. If treatments are equivalent, then under the paradigm, it does not matter which treatment is selected. Newer approaches for increasing trial efficiency, including an adaptive platform trial design, may mitigate limitations of the selection design.

PMID: 31608711 [PubMed - as supplied by publisher]

Long-term chemogenetic suppression of spontaneous seizures in a mouse model for temporal lobe epilepsy.

Epilepsia. 2019 Oct 13;:

Authors: Desloovere J, Boon P, Larsen LE, Merckx C, Goossens MG, Van den Haute C, Baekelandt V, De Bundel D, Carrette E, Delbeke J, Meurs A, Vonck K, Wadman W, Raedt R

Abstract
OBJECTIVE: More than one-third of patients with temporal lobe epilepsy (TLE) continue to have seizures despite treatment with antiepileptic drugs, and many experience severe drug-related side effects, illustrating the need for novel therapies. Selective expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) allows cell-type-specific reduction of neuronal excitability. In this study, we evaluated the effect of chemogenetic suppression of excitatory pyramidal and granule cell neurons of the sclerotic hippocampus in the intrahippocampal mouse model (IHKA) for temporal lobe epilepsy.
METHODS: Intrahippocampal IHKA mice were injected with an adeno-associated viral vector carrying the genes for an inhibitory DREADD hM4Di in the sclerotic hippocampus or control vector. Next, animals were treated systemically with different single doses of clozapine-N-oxide (CNO) (1, 3, and 10 mg/kg) and clozapine (0.03 and 0.1 mg/kg) and the effect on spontaneous hippocampal seizures, hippocampal electroencephalography (EEG) power, fast ripples (FRs) and behavior in the open field test was evaluated. Finally, animals received prolonged treatment with clozapine for 3 days and the effect on seizures was monitored.
RESULTS: Treatment with both CNO and clozapine resulted in a robust suppression of hippocampal seizures for at least 15 hours only in DREADD-expressing animals. Moreover, total EEG power and the number of FRs were significantly reduced. CNO and/or clozapine had no effects on interictal hippocampal EEG, seizures, or locomotion/anxiety in the open field test in non-DREADD epileptic IHKA mice. Repeated clozapine treatment every 8 hours for 3 days resulted in almost complete seizure suppression in DREADD animals.
SIGNIFICANCE: This study shows the potency of chemogenetics to robustly and sustainably suppress spontaneous epileptic seizures and pave the way for an epilepsy therapy in which a systemically administered exogenous drug selectively modulates specific cell types in a seizure network, leading to a potent seizure suppression devoid of the typical drug-related side effects.

PMID: 31608439 [PubMed - as supplied by publisher]

Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C.

J Clin Transl Hepatol. 2019 Sep 28;7(3):221-225

Authors: Wei L, Shang J, Ma Y, Xu X, Huang Y, Guan Y, Duan Z, Zhang W, Gao Z, Zhang M, Li J, Jia J, Yang Y, Wen X, Wang M, Jia Z, Ning B, Chen Y, Qi Y, Du J, Jiang J, Tong L, Xie Y, Wu JJ

Abstract
Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 μg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9-99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082.

PMID: 31608213 [PubMed]

A Diagnostically Challenging Infusion Reaction-Kounis, Takotsubo, or the ATAK!

JAMA Intern Med. 2019 Jan 01;179(1):99-100

Authors: Mustehsan MH, Jahufar F, Arora S

PMID: 30398531 [PubMed - indexed for MEDLINE]

Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: an open-label Phase IIIb/IV study (PROFILE).

J Antimicrob Chemother. 2018 12 01;73(12):3430-3441

Authors: Högenauer C, Mahida Y, Stallmach A, Marteau P, Rydzewska G, Ivashkin V, Gargalianos-Kakolyris P, Michon I, Adomakoh N, Georgopali A, Tretter R, Karas A, Reinisch W

Abstract
Objectives: Inflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD.
Methods: The plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591.
Results: Median Tmax of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1-2 h across Days 1, 5 and 10. Cmax ranges were 1.2-154 ng/mL for fidaxomicin and 4.7-555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8-2170 μg/g for fidaxomicin and 0-1940 μg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death.
Conclusions: Maximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD.

PMID: 30260412 [PubMed - indexed for MEDLINE]

Identifying signals of interest when screening for drug-outcome associations in health care data.

Br J Clin Pharmacol. 2018 09;84(9):1865-1867

Authors: Pottegård A, Hallas J, Wang SV, Gagne JJ

PMID: 29862551 [PubMed - indexed for MEDLINE]

Patient involvement is essential in identifying drug-related problems.

Br J Clin Pharmacol. 2018 09;84(9):2048-2058

Authors: Kari H, Kortejärvi H, Airaksinen M, Laaksonen R

Abstract
AIMS: The aim of this study is to evaluate how critical patient involvement is in pharmacist-led clinical medication reviews and in identifying the most significant clinical drug-related problems (DRPs).
METHODS: Pharmacist-led clinical medication reviews were conducted with 161 consenting patients aged ≥75 years with at least seven prescribed medicines, living independently at home in Finland. A pharmacist, a nurse and a physician evaluated the clinical significance of the DRPs identified during the patient interview at an interprofessional case conference. It was evaluated whether the most significant clinical DRPs could also have been identified through reviewing the medication list only or the medication list and certain patient details.
RESULTS: Altogether, the 111 most significant clinical DRPs were evaluated. Only 6% could have been identified through reviewing the medication list only, and 16% through reviewing the medication list and certain patient details. Hence, 84% of the most significant clinical DRPs could only have been identified with patient involvement. The most common DRPs were: poor therapy control (25%); nonoptimal drug (22%); intentional nonadherence (12%); and additional drug needed (11%). patient involvement was critical when identifying DRPs related to additional drug needed, unintentional nonadherence, use of over-the-counter medicines or dietary supplements, or contradictions in counselling.
CONCLUSION: Patient involvement is essential when identifying clinical DRPs. Indeed, poor therapy control, nonoptimal drug use, intentional or unintentional nonadherence might otherwise be missed.

PMID: 29774588 [PubMed - indexed for MEDLINE]

No differences in olanzapine- and risperidone-related weight gain between women and men: a meta-analysis of short- and middle-term treatment.

Acta Psychiatr Scand. 2018 08;138(2):110-122

Authors: Schoretsanitis G, Drukker M, Van Os J, Schruers KRJ, Bak M

Abstract
OBJECTIVE: A plethora of data deriving from single studies as well as meta-analyses demonstrates that weight gain is associated with the exposure to the majority of antipsychotics (AP). However, potential sex differences have widely evaded the attention of AP treatment trials. It is hypothesised that female patients gain more weight compared with male patients due to their enhanced susceptibility to adverse drug reactions.
METHOD: A meta-analysis was conducted using clinical trials of AP that reported weight change separately for female and male patients. Duration of AP use was stratified in four categories: <6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots were generated for men and women separately, stratified by AP as well as by duration of use. Sex differences were tested by performing meta-regression.
RESULTS: Data of 26 studies were used in the present analysis because sufficient data were available only for olanzapine, risperidone and the no-medication group. Both female and male patients showed considerable weight gain after switch or initiate of olanzapine or risperidone, but meta-regression analyses did not show significant sex differences.
CONCLUSION: The present meta-analysis revealed that sex differences in AP-related weight gain have been under investigated hampering the detection of sex-specific patterns. In chronic patients switching to olanzapine or risperidone receiving short-or middle-term treatment, AP were associated with weight gain in both sex subgroups and no significant differences were reported.

PMID: 29602172 [PubMed - indexed for MEDLINE]

Factors influencing adherence to tuberculosis treatment in Asmara, Eritrea: a qualitative study.

J Health Popul Nutr. 2018 01 05;37(1):1

Authors: Gebreweld FH, Kifle MM, Gebremicheal FE, Simel LL, Gezae MM, Ghebreyesus SS, Mengsteab YT, Wahd NG

Abstract
BACKGROUND: Non-adherence to tuberculosis (TB) treatment is an important barrier for TB prevention and control. Poor adherence may result in prolonged disease infectiousness, drug resistance, relapse and death. The aim of this study was to assess factors influencing adherence to tuberculosis treatment in selected health facilities in Asmara, Eritrea.
METHODS: A qualitative study which included in-depth interviews with 12 TB patients, three focus group discussions in selected health facilities in which one group comprised eight patients and key informant interviews with three health workers. Data analysis was done by translating and transcribing the verbatim of the interviews and focus group discussions. Transcribed data was then analysed using thematic framework procedure.
RESULTS: This study found that patients lacked knowledge about the cause, transmission and duration of treatment of TB. The most common reason mentioned for discontinuing treatment was the patient "felt cured". Almost half of the respondents did not know the standard treatment duration and the consequences they face if they halt treatment. Patients reported losing their job when their diagnosis was known, were too ill to continue working or unable to find daily work due to time-consuming treatment arrangements. With few exceptions, the majority of patients reported that the short distance to the clinic encouraged them to attend regular treatment follow-up. Most of the respondents were unable to get enough food, leading to stress and feelings of hopelessness. Lack of social support for most of the patients was a critical factor for adherence as were stigma, medication side effects and long treatment duration. Recognized as an enabler to treatment adherence, health workers had good communication and positive attitude towards their patients.
CONCLUSION: Lack of knowledge, loss of income, stigma and lack of social support, drug side effects and long treatment duration emerged as important barriers for treatment adherence. Short distances to health facilities, good communication and accepting attitude of health care providers emerged as enablers for treatment adherence. For better treatment adherence, comprehensive health education at treatment sites, patient's family members and the community at large and strengthening of social support structures need to be addressed.

PMID: 29304840 [PubMed - indexed for MEDLINE]

[Rheumatological emergency on the edge of intensive care medicine].

Z Rheumatol. 2019 Oct 11;:

Authors: Härle P

Abstract
In rheumatological practice situations repeatedly occur where critical problems which need to be quickly addressed in order to prevent permanent damage to the patient. The focus of this article is on rapidly progressive inflammatory diseases, severe side effects of many medications and complications of infections during immunosuppressive treatment.

PMID: 31605194 [PubMed - as supplied by publisher]

Exploring the drug-induced anemia signals in children using electronic medical records.

Expert Opin Drug Saf. 2019 Oct;18(10):993-999

Authors: Fan DF, Yu YC, Ding XS, Nie XL, Wei R, Feng XY, Peng XX, Gao MM, Jia LL, Wang XL

Abstract
Objectives: The objectives were to identify drugs related with anemia in children and evaluate the novelty of these correlations. Methods: The authors established a two-step method for detecting the relationship between drugs and anemia using electronic medical records (EMRs), which were obtained from 247,136 patients in Beijing Children's Hospital between 2007 and 2017. The authors extracted potential drugs by mining cases for hemoglobin abnormalities from the EMR and then performed a retrospective cohort study to correlate them with anemia by calculating the matched odds ratios and 95% confidence interval using unconditional logistic regression analysis. Results: In total, nine positive drug-anemia associations were identified. Among them, the correlations of drugs fluconazole (OR 3.95; 95%CI: 2.65-5.87) and cefathiamidine (OR 3.49; 95%CI: 2.94-4.15) with anemia were considered new signals in both children and adults. Three associations of drugs, vancomycin, cefoperazone-sulbactam and ibuprofen, with anemia were considered new signals in children. Conclusion: The authors detected nine signals of drug-induced anemia, including two new signals in children and adults and three new signals in children. This study could serve as a model for using EMR and automatic mining to monitor adverse drug reaction signals in the pediatric population.

PMID: 31315002 [PubMed - indexed for MEDLINE]

Can doctors identify older patients at risk of medication harm following hospital discharge? A multicentre prospective study in the UK.

Br J Clin Pharmacol. 2018 10;84(10):2344-2351

Authors: Parekh N, Stevenson JM, Schiff R, Graham Davies J, Bremner S, Van der Cammen T, Harchowal J, Rajkumar C, Ali K, PRIME study group

Abstract
AIMS: Medication-related harm (MRH) is common in older adults following hospital discharge. In resource-limited health systems, interventions to reduce this risk can be targeted at high-risk patients. This study aims to determine whether (1) doctors can predict which older patients will experience MRH requiring healthcare following hospital discharge, (2) clinical experience and confidence in prediction influence the accuracy of the prediction.
METHODS: This was a multicentre observational prospective study involving five teaching hospitals in England between September 2013 and November 2015. Doctors discharging patients (aged ≥65 years) from medical wards predicted the likelihood of their patient experiencing MRH requiring healthcare (hospital readmission or community healthcare) in the initial 8-week period post-discharge. Patients were followed up by senior pharmacists to determine MRH occurrence.
RESULTS: Data of 1066 patients (83%) with completed predictions and follow-up, out of 1280 recruited patients, were analysed. Patients had a median age of 82 years (65-103 years), and 58% were female. Most predictions (85%) were made by junior doctors with less than 5 years' clinical experience. There was no relationship between doctors' predictions and patient MRH (OR 1.10, 95% CI 0.82-1.46, P = 0.53), irrespective of years of clinical experience. Doctors' predictions were more likely to be accurate when they reported higher confidence in their prediction, especially in predicting MRH-associated hospital readmissions (OR 1.58, 95% CI 1.42-1.76, P < 0.001).
CONCLUSIONS: Clinical judgement of doctors is not a reliable tool to predict MRH in older adults post-discharge.

PMID: 29957885 [PubMed - indexed for MEDLINE]

Is lithium monitoring NICE? Lithium monitoring in a UK secondary care setting.

J Psychopharmacol. 2018 04;32(4):408-415

Authors: Nikolova VL, Pattanaseri K, Hidalgo-Mazzei D, Taylor D, Young AH

Abstract
BACKGROUND: Lithium is widely used for the treatment of bipolar disorder. Owing to its narrow therapeutic index and side-effect profile, regular monitoring of serum levels, renal and thyroid function has been recommended by all major guidelines on lithium use.
OBJECTIVES: We investigated whether lithium monitoring during maintenance phase treatment in clinical practice meets the latest recommendation by the National Institute for Health and Clinical excellence (i.e. lithium levels between 0.6 and 1.0 mmol/L and lithium level, thyroid and renal function tests every 6 months) in one of the largest mental health organizations in Europe, the South London and Maudsley (SLaM) NHS Foundation Trust.
METHODS: Retrospective data were extracted from SLaM's Clinical Record Interactive Search (CRIS) system. Adult patients with a psychiatric disorder who were on lithium at any point during the period January 2012-January 2016 and had at least one lithium level test result in the system were included in the analyses.
RESULTS: A total of 2639 lithium level tests results were retrieved for 412 patients. Overall, the serum level was within the recommended range in 50.7% of all tests, below the range in 42.4% and above in 6.9%. Lithium level, renal and thyroid function tests were performed at the recommended frequency of 6 months (or less) in 76.2%, 72.7% and 60.2% of patients, respectively.
CONCLUSION: These data demonstrate that there is a gap between the NICE 2014 recommendation and lithium monitoring practice in secondary care, with a high number of lithium level results below the therapeutic minimum. Reminder strategies for secondary care practitioners, shared care agreements or a central registry for lithium users could improve monitoring performance.

PMID: 29552933 [PubMed - indexed for MEDLINE]

Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized, double-blind, 8-week study.

J Clin Hypertens (Greenwich). 2018 01;20(1):150-158

Authors: Cheung DG, Aizenberg D, Gorbunov V, Hafeez K, Chen CW, Zhang J

Abstract
A majority of patients with hypertension fail to achieve blood pressure (BP) control despite treatment with commonly prescribed drugs. This randomized, double-blind phase III trial assessed the superiority of sacubitril/valsartan 200 mg (97/103 mg) to continued olmesartan 20 mg in reducing ambulatory systolic BP after 8-week treatment in patients with mild to moderate essential hypertension uncontrolled with olmesartan 20 mg alone. A total of 376 patients were randomized to receive either sacubitril/valsartan (n = 188) or olmesartan (n = 188). Superior reductions in 24-hour mean ambulatory systolic BP were observed in the sacubitril/valsartan group vs the olmesartan group (-4.3 mm Hg vs -1.1 mm Hg, P < .001). Reductions in 24-hour mean ambulatory diastolic BP and pulse pressure and office systolic BP and diastolic BP were significantly greater with sacubitril/valsartan vs olmesartan (P < .014). A greater proportion of patients achieved BP control with sacubitril/valsartan vs olmesartan. The overall incidence of adverse events was comparable between the groups. Compared with continued olmesartan, sacubitril/valsartan was more effective and generally safe in patients with hypertension uncontrolled with olmesartan 20 mg.

PMID: 29338113 [PubMed - indexed for MEDLINE]

Use of Medicines that May Exacerbate Heart Failure in Older Adults: Therapeutic Complexity of Multimorbidity.

Drugs Aging. 2019 05;36(5):471-479

Authors: Caughey GE, Shakib S, Barratt JD, Roughead EE

Abstract
BACKGROUND: Multimorbidity is common in older patients with heart failure (HF), complicating therapeutic management and increasing the risk of harm.
OBJECTIVE: This study sought to examine the prevalence of medicines for the treatment of comorbid conditions potentially associated with harm in older people, before and after HF hospitalization.
METHODS: A retrospective cohort study of older people hospitalized with a primary diagnosis of HF over a 12-month period was conducted using administrative health claims data from the Department of Veterans' Affairs (DVA) Australia. We examined the prevalence of medicines that may exacerbate or worsen HF as defined by the American Heart Association (AHA) and Australian HF clinical guidelines, in the 30 days prior and 120 days before and after discharge for HF.
RESULTS: A total of 4069 older adults were hospitalized for HF during the study period; almost 60% (n = 2435) received at least one medicine associated with an increased risk of harm before hospitalization, with the majority (66.7%, n = 1623) dispensed in the 30 days prior. A small but significant reduction after hospitalization was observed, but 56% (n = 1638) received at least one of these medicines after hospitalization (p = 0.001). Over one-quarter received two or more medicines before hospitalization, and this only reduced to 22% post-hospitalization (p < 0.0001).
CONCLUSIONS: Little change in the prescribing of potentially harmful medicines for HF was observed; 56% of older adults received at least one following hospitalization for HF, highlighting the therapeutic complexity of multimorbidity in HF. Use of the AHA list to facilitate identification of potentially harmful medicines, followed by prioritization of treatment goals and appropriate risk mitigation are needed to facilitate reduction in hospitalization for patients with HF with multimorbidity.

PMID: 30875020 [PubMed - indexed for MEDLINE]

Potentially Inappropriate Prescribing and Related Hospital Admissions in Geriatric Patients: A Comparative Analysis between the STOPP and START Criteria Versions 1 and 2.

Drugs Aging. 2019 05;36(5):453-459

Authors: Thevelin S, Mounaouar LE, Marien S, Boland B, Henrard S, Dalleur O

Abstract
BACKGROUND: Older persons are at significant risk of drug-related admissions (DRAs). We previously demonstrated that 27% of hospitalizations in geriatric patients were associated with potentially inappropriate medicines (PIMs) and/or potential prescribing omissions (PPOs) identified by the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) criteria version 1 (v1). The updated STOPP/START criteria version 2 (v2) comprised a 31% increase in prescribing criteria.
OBJECTIVE: As a secondary analysis of our study conducted in 2008, we aimed to compare the prevalence and types of DRAs identified by STOPP/START.v1 and STOPP/START.v2.
METHODS: We applied the STOPP/START.v2 criteria to a subset of 100 consecutively admitted geriatric patients selected from our original cross-sectional study of 302 patients. A geriatrician and a pharmacist adjudicated whether the identified PIMs and PPOs were related to acute hospitalization. Admissions were defined as DRAs if the identified PIM(s) and/or PPO(s) were related to the main cause of admission or played a significant contributory role in the admission.
RESULTS: The median patient age was 83 years and the median number of medications at home was 8. Compared with STOPP/START.v1, STOPP/START.v2 not only yielded more instances of inappropriate prescribing but also targeted significantly more PIMs and PPOs associated with preventable DRAs (23% vs. 40% of all admissions, p < 0.001). PIMs of fall-risk-increasing drugs, and PPOs of musculoskeletal and cardiovascular system drugs, were most frequently associated with DRAs.
CONCLUSION: The latter instances of inappropriate prescribing with major clinical relevance warrant particular attention during medication review in older persons.

PMID: 30694444 [PubMed - indexed for MEDLINE]

Addressing New Diagnostic and Treatment Challenges Associated With a New Age of Cancer Treatment.

Ann Emerg Med. 2019 01;73(1):88-90

Authors: Bischof JJ, Presley CJ, Caterino JM

PMID: 30243546 [PubMed - indexed for MEDLINE]

Low to Intermediate Dose Atropine Administration During Dobutamine Stress Echocardiography in the Pre-Liver Transplant Population.

Prog Transplant. 2018 12;28(4):361-367

Authors: Snipelisky D, Shipman J, Olson N, Pellikka P, Aqel B, McCully R, Watt K

Abstract
INTRODUCTION: Dobutamine stress echocardiography (DSE) is frequently used to screen for obstructive coronary artery disease in the pre-liver transplant evaluation. Although atropine is a commonly used adjunctive medication, no study has evaluated its side effect profile in patients with end-stage liver disease (ESLD).
RESEARCH QUESTION: What is the safety of atropine in candidates undergoing pre-liver transplant evaluation when atropine is used in stress testing?
DESIGN: This multicenter, prospective study enrolled patients over a 6-month period undergoing pre-liver transplant evaluation. Each patient completed a questionnaire assessing anticholinergic-related symptoms within 24 hours of testing and 48 hours following. Comparisons were made among patients receiving any atropine dose versus those who did not and among patients receiving at least 1 mg atropine and those receiving less/none.
RESULTS: Forty patients were evaluated, and 32 (80%) had adjunctive atropine administered. No differences in clinical characteristics were noted. In comparisons among patients receiving any dose of atropine with those who did not, questionnaire results indicated a higher rate of nausea prior to testing and higher overall symptom severity following testing in patients not receiving atropine. In comparisons among patients receiving less than 1 mg atropine with those receiving at least 1 mg atropine, no difference in pre- or posttesting questionnaire responses was present. No patient in the study required reversal agents or hospitalization within 7 days of testing.
CONCLUSIONS: Atropine, a hepatically metabolized medication, did not predispose patients with ESLD to an increased symptom burden, and clinical outcomes related to DSE were unaffected.

PMID: 30222085 [PubMed - indexed for MEDLINE]

A novel multi-parametric high content screening assay in ciPTEC-OAT1 to predict drug-induced nephrotoxicity during drug discovery.

Arch Toxicol. 2018 10;92(10):3175-3190

Authors: Sjögren AK, Breitholtz K, Ahlberg E, Milton L, Forsgard M, Persson M, Stahl SH, Wilmer MJ, Hornberg JJ

Abstract
Drug-induced nephrotoxicity is a major concern in the clinic and hampers the use of available treatments as well as the development of innovative medicines. It is typically discovered late during drug development, which reflects a lack of in vitro nephrotoxicity assays available that can be employed readily in early drug discovery, to identify and hence steer away from the risk. Here, we report the development of a high content screening assay in ciPTEC-OAT1, a proximal tubular cell line that expresses several relevant renal transporters, using five fluorescent dyes to quantify cell health parameters. We used a validation set of 62 drugs, tested across a relevant concentration range compared to their exposure in humans, to develop a model that integrates multi-parametric data and drug exposure information, which identified most proximal tubular toxic drugs tested (sensitivity 75%) without any false positives (specificity 100%). Due to the relatively high throughput (straight-forward assay protocol, 96-well format, cost-effective) the assay is compatible with the needs in the early drug discovery setting to enable identification, quantification and subsequent mitigation of the risk for nephrotoxicity.

PMID: 30155723 [PubMed - indexed for MEDLINE]