Leuk Lymphoma. 2021 Feb 13:1-13. doi: 10.1080/10428194.2021.1881509. Online ahead of print.

ABSTRACT

Bromodomain and extra-terminal (BET) proteins can drive carcinogenesis and therapy resistance. RO6870810 (RO) is a novel, small-molecule BET inhibitor. We conducted a study in 32 patients with relapsed/refractory acute myeloid leukemia and hypomethylating agent-refractory myelodysplastic syndrome (NCT02308761). Pharmacodynamic assessments showed decreases in CD11b in peripheral blood mononuclear cells at RO concentrations above 120 ng/mL. Treatment emergent adverse events were generally mild and the most frequent were fatigue, injection site reactions, diarrhea, decreased appetite and nausea. There were no treatment-related deaths. Potential drug-related dose limiting toxicities included decreased appetite, congestive cardiac failure, hypertension, fatigue, increased conjugated bilirubin and increased gamma glutamyltransferase. One AML patient achieved complete remission after withdrawal from study. Eleven AML patients experienced SD. For AML, the median OS was 72.0 days. For MDS, two patients experienced SD. Further development of RO as monotherapy was discontinued due to lack of efficacy, but combinations with other agents are under consideration.

PMID:33586590 | DOI:10.1080/10428194.2021.1881509

Cancer Med. 2021 Feb 14. doi: 10.1002/cam4.3771. Online ahead of print.

ABSTRACT

BACKGROUND: Currently, there are no randomized trials on the effect of antiangiogenic therapy in patients with esophageal squamous cell carcinoma (ESCC). The following study investigated the efficacy and safety of anlotinib in patients with advanced ESCC who were previously treated with chemotherapy.

METHODS: This randomized, placebo-controlled, double-blind phase 2 trial (NCT02649361) was conducted in 13 Chinese hospitals. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC who were previously treated with chemotherapy, and were randomly assigned (2:1) to receive oral anlotinib 12 mg or placebo on days 1-14 (repeated every 21 days). The primary endpoint was progression-free survival (PFS).

RESULTS: One hundred and sixty-five patients were randomly assigned to the anlotinib (n = 110) or the placebo (n = 55) arm. Median PFS was 3.02 months (95% CI 2.63-3.65) in the anlotinib group and 1.41 months (95% CI 1.38-1.41) in the placebo group (hazard ratio 0.46 [95% CI 0.32-0.66]; p < 0.001). The most common treatment-related adverse events of grade 3 or 4 were hypertension (17 [16%] patients), decreased appetite (6 [6%] patients), and hyponatremia (4 [4%] patients) in the anlotinib group and decreased appetite (2 [4%] patients) in the placebo group. Three (3%) deaths in the anlotinib group were considered as drug related, while there were no treatment-related deaths in the placebo group.

CONCLUSIONS: The use of anlotinib in previously treated, recurrent, or metastatic ESCC patients significantly improved PFS compared with placebo. Our findings suggest that antiangiogenesis might be an important therapeutic target in advanced ESCC.

CLINICAL TRIALS REGISTRATION: Study of Anlotinib in Patients With Esophageal Squamous Cell Carcinoma (ALTER1102), NCT02649361.

PMID:33586360 | DOI:10.1002/cam4.3771

J Investig Med High Impact Case Rep. 2021 Jan-Dec;9:2324709620984610. doi: 10.1177/2324709620984610.

ABSTRACT

Nitrofurantoin is considered optimal treatment for acute uncomplicated cystitis by the Infectious Diseases Society of America and is being increasingly recommended due to microbial resistance to sulfamethoxazole/trimethoprim and various fluoroquinolone antibiotics. Adverse effects of nitrofurantoin are generally considered mild, with gastrointestinal complaints being the most common. However, there have been isolated case reports describing a more severe systemic inflammatory response syndrome-like reaction, which leads to diagnostic challenges and treatment complications. We report the case of a patient with repeat episodes of systemic inflammatory response syndrome secondary to nitrofurantoin, which was initially attributed to recurrent urinary tract infections.

PMID:33583214 | DOI:10.1177/2324709620984610

Carbapenem Therapeutic Drug Monitoring in Critically Ill Adult Patients and Clinical Outcomes: A Systematic Review with Meta-Analysis.

Antibiotics (Basel). 2021 Feb 10;10(2):

Authors: Lechtig-Wasserman S, Liebisch-Rey H, Diaz-Pinilla N, Blanco J, Fuentes-Barreiro YV, Bustos RH

Abstract
Drug monitoring is one strategy of antibiotic stewardship to face antimicrobial resistance. This strategy could have a determinant role in critically ill patients treated with carbapenems to overcome pharmacokinetic variability, reduce the risk of subtherapeutic dosage or toxicity, and reduce the risks inherent to treatment. However, the effectiveness of therapeutic drug monitoring (TDM) is unknown. This paper aims to identify TDM effectiveness in critically ill patients treated with carbapenems. English and ClinicalTrials.gov databases were searched to identify relevant studies evaluating carbapenem TDM. Randomized controlled trials (RCTs) and comparative cohort studies were selected for inclusion if they compared carbapenem TDM to standard care in adult critically ill or sepsis/septic shock patients. The primary outcome was mortality. Secondary outcomes included morbidity, clinical cure, microbiological eradication, antimicrobial resistance, drug-related side effects, and achievement of target plasma concentrations. Overall, performing carbapenem TDM was not associated with a decrease in mortality. However, it could be evidence for a relationship with clinical cure as well as target attainment. Some studies found favorable outcomes related to clinical and microbiological responses, such as lower procalcitonin levels at the end of the monitored therapy compared to standard care. For the primary and secondary outcomes analyzed, strong evidence was not identified, which could be due to the size, risk of bias, and design of selected studies.

PMID: 33578672 [PubMed - as supplied by publisher]

Prescribing cascades and medications most frequently involved in pain therapy: a review.

Eur Rev Med Pharmacol Sci. 2021 Jan;25(2):1034-1041

Authors: Nunnari P, Ceccarelli G, Ladiana N, Notaro P

Abstract
OBJECTIVE: The aging of the population and chronic pain represents topical issues in developed countries. These often translate into polypharmacy, inappropriate medications, and adverse drug events, with the risk of misinterpreting these latter with new medical conditions, generating what is referred to prescribing cascade. Prescribing cascades may lead to the prescription of new drugs, which could cause new potential side effects and unnecessary costs for individuals and healthcare systems. Therefore, the purpose of our review was to collect a good deal of prescribing cascades examples involving pain therapy medicines, to help clinicians minimize drug-related clinical outcomes.
MATERIALS AND METHODS: We search in MEDLINE database through PubMed, including 31 studies and 80 different examples of prescribing cascades.
RESULTS: The medications most commonly resulting in the initial drug therapy prescribed were represented by psychoanaleptics (27/80, 33.7%). Among adverse drug events, the most common one, misinterpreted as a new medical condition, was represented by tremor and extrapyramidal symptoms (20/80, 25%). As regards the new drug therapies prescribed for adverse drug events, the therapeutic subgroups most commonly resulting in the new drug therapy prescribed were represented by psycholeptics (12/80, 15%), and by anti-Parkinson drugs (12/80, 15%).
CONCLUSIONS: This study provides a list of several examples of prescribing cascades in pain medicine and is essential to raise awareness of the potential dangers they could involve in all patient populations. Collaboration between clinicians and clinical pharmacologists may lead to more appropriate polypharmacy schemes.

PMID: 33577059 [PubMed - as supplied by publisher]

Mass balance and pharmacokinetics of an oral dose of 14 C-napabucasin in healthy adult male subjects.

Pharmacol Res Perspect. 2021 Feb;9(1):e00722

Authors: Dai X, Karol MD, Hitron M, Hard ML, Blanchard JE, Eraut NCJE, Rich N, Gufford BT

Abstract
This phase 1, open-label study assessed14 C-napabucasin absorption, metabolism, and excretion, napabucasin pharmacokinetics, and napabucasin metabolites (primary objectives); safety/tolerability were also evaluated. Eight healthy males (18-45 years) received a single oral 240-mg napabucasin dose containing ~100 μCi14 C-napabucasin. Napabucasin was absorbed and metabolized to dihydro-napabucasin (M1; an active metabolite [12.57-fold less activity than napabucasin]), the sole major circulating metabolite (median time to peak concentration: 2.75 and 2.25 h, respectively). M1 plasma concentration versus time profiles generally mirrored napabucasin; similar arithmetic mean half-lives (7.14 and 7.92 h, respectively) suggest M1 formation was rate limiting. Napabucasin systemic exposure (per Cmax and AUC) was higher than M1. The total radioactivity (TRA) whole blood:plasma ratio (AUClast : 0.376; Cmax : 0.525) indicated circulating drug-related compounds were essentially confined to plasma. Mean TRA recovery was 81.1% (feces, 57.2%; urine, 23.8%; expired air, negligible). Unlabeled napabucasin and M1 recovered in urine accounted for 13.9% and 11.0% of the dose (sum similar to urine TRA recovered); apparent renal clearance was 8.24 and 7.98 L/h. No uniquely human or disproportionate metabolite was quantified. Secondary glucuronide and sulfate conjugates were common urinary metabolites, suggesting napabucasin was mainly cleared by reductive metabolism. All subjects experienced mild treatment-emergent adverse events (TEAEs), the majority related to napabucasin. The most commonly reported TEAEs were gastrointestinal disorders. There were no clinically significant laboratory, vital sign, electrocardiogram, or physical examination changes. Napabucasin was absorbed, metabolized to M1 as the sole major circulating metabolite, and primarily excreted via feces. A single oral 240-mg dose was generally well tolerated.

PMID: 33576192 [PubMed - in process]

Real-world safety and effectiveness of radium-223 in Japanese patients with castration-resistant prostate cancer (CRPC) and bone metastasis: exploratory analysis, based on the results of post-marketing surveillance, according to prior chemotherapy status and in patients without concomitant use of second-generation androgen-receptor axis-targeted agents.

Int J Clin Oncol. 2021 Feb 11;:

Authors: Uemura H, Masumori N, Takahashi S, Hosono M, Kinuya S, Sunaya T, Horio T, Okayama Y, Kakehi Y

Abstract
BACKGROUND: Based on results from Japanese post-marketing surveillance, exploratory analyses were performed to investigate real-world outcomes of radium-223 for metastatic CRPC (mCRPC) according to patient characteristics.
METHODS: This non-interventional, prospective study enrolled mCRPC patients selected for radium-223 treatment in clinical practice. Six-month safety and effectiveness were evaluated in subgroups who had/had not received prior chemotherapy (prior-chemo/no prior-chemo groups), and a subgroup who had not received concomitant androgen-receptor axis-targeted agents (ARATs).
RESULTS: In the overall population (n = 296), the prior-chemo group (n = 126) tended to have more bone metastases, more analgesic use, and higher prostate-specific antigen values than the no prior-chemo group (n = 170). Incidences of treatment-emergent adverse events (TEAEs), drug-related TEAEs, and ≥ grade 3 drug-related hematological TEAEs were 47% vs. 53%, 25% vs. 29%, and 4% vs. 7% in the no prior-chemo and prior-chemo groups, respectively. Incidences of TEAEs (61%), drug-related TEAEs (36%), and ≥ grade 3 drug-related hematological events (12%) were numerically higher in 33 patients who had received two lines of prior chemotherapy. Multivariate analysis showed that two lines of prior chemotherapy, and hemoglobin, platelet, and lactate dehydrogenase values were baseline factors significantly related to ≥ grade 2 platelet count decreased. Safety and effectiveness in patients without concomitant ARATs (n = 201) were similar to those in the overall population.
CONCLUSION: In a real-life setting, radium-223 was well tolerated irrespective of prior chemotherapy, but relatively higher incidences of TEAEs and hematotoxicities were suggested in patients with two lines of prior chemotherapy, possibly reflecting more advanced disease. Radium-223 safety and effectiveness in patients without concomitant ARATs were favorable.

PMID: 33575828 [PubMed - as supplied by publisher]

Clozapine Intoxication in COVID-19.

Am J Psychiatry. 2021 02 01;178(2):123-127

Authors: Tio N, Schulte PFJ, Martens HJM

PMID: 33517757 [PubMed - indexed for MEDLINE]

Palbociclib use with grade 3 neutropenia in hormone receptor-positive metastatic breast cancer.

Breast Cancer Res Treat. 2020 Aug;183(1):107-116

Authors: Ham A, Kim MH, Kim GM, Kim JH, Kim JY, Park HS, Park S, Cho YU, Park BW, Kim SI, Sohn J

Abstract
PURPOSE: Neutropenia is the most common toxicity of CDK4/6 inhibitors, causing frequent dose interruptions. However, CDK4/6 inhibitor-induced neutropenia shows a benign clinical course in contrast to that caused by chemotherapy. Here, we investigated the safety of a new dose scheme for palbociclib, which avoids dose delays or reductions due to afebrile grade 3 neutropenia.
METHODS: A consecutive cohort of ER( +)/HER2( -) advanced breast cancer patients who received palbociclib between 2017 and 2018 was analyzed. The patients were classified into Group 1 (patients who maintained palbociclib dose with afebrile grade 3 neutropenia), Group 2 (patients who experienced any dose modification with afebrile grade 3 neutropenia), and Group 3 (patients without afebrile grade 3 neutropenia). The primary endpoint was febrile neutropenia incidence; other toxicities were compared with those of the PALOMA-2 trial.
RESULTS: Among the 107 patients, 54.2%, 22.4%, and 23.4% were classified into Groups 1, 2, and 3, respectively. There was no febrile neutropenia in Groups 1 and 2 during palbociclib treatment. Group 1 showed higher incidence of thrombocytopenia (all-grade, 32.8%; grade 3-4, 8.6%) than Group 2 and the PALOMA-2 data, but there was no bleeding related to thrombocytopenia. Group 1 showed higher incidence of all-grade non-hematologic adverse events than Group 2; only one grade 3 non-hematologic toxicity was observed in Group 1. There were no treatment-related hospitalizations or deaths in Group 1.
CONCLUSIONS: Thus, omitting palbociclib dose modification with afebrile grade 3 neutropenia is safe and tolerable without febrile neutropenia events. This scheme could be useful to avoid unnecessary reductions in palbociclib doses in future practice.

PMID: 32577940 [PubMed - indexed for MEDLINE]

Symptomatic digoxin toxicity in a patient on haemodialysis.

BMJ Case Rep. 2020 Jun 16;13(6):

Authors: Delicata L, Gatt A, Paris JL, Bonello J

Abstract
We present a man undergoing regular haemodialysis sessions, who presented with non-specific symptoms of nausea, vomiting and light-headedness. He was found to have significantly raised serum digoxin concentrations, as well as a heart rate of 30 beats per minutes. An ECG showed complete heart block. He has a history of non-ischaemic dilated cardiomyopathy with resistant supraventricular and ventricular tachycardias and was on concomitant beta-blockade and digoxin. On questioning, he reported a gradual decline in his residual urine output over the past 6 months. He was reviewed by the cardiology team and required both pharmacological therapy for reversal of digoxin toxicity and temporary pacing in view of significant bradyarrhythmias. The beta-blockade and digoxin were discontinued. He was kept on continuous monitoring at the Cardiac Critical Care Unit. His symptoms resolved spontaneously once digoxin-specific antibody fragments were administered and temporary pacing successfully performed.

PMID: 32546555 [PubMed - indexed for MEDLINE]

Reducing medicine-induced deterioration and adverse reactions (ReMInDAR) trial: study protocol for a randomised controlled trial in residential aged-care facilities assessing frailty as the primary outcome.

BMJ Open. 2020 04 22;10(4):e032851

Authors: Lim R, Bereznicki L, Corlis M, Kalisch Ellett LM, Kang AC, Merlin T, Parfitt G, Pratt NL, Rowett D, Torode S, Whitehouse J, Andrade AQ, Bilton R, Cousins J, Kelly L, Schubert C, Williams M, Roughead EE

Abstract
INTRODUCTION: Many medicines have adverse effects which are difficult to detect and frequently go unrecognised. Pharmacist monitoring of changes in signs and symptoms of these adverse effects, which we describe as medicine-induced deterioration, may reduce the risk of developing frailty. The aim of this trial is to determine the effectiveness of a 12-month pharmacist service compared with usual care in reducing medicine-induced deterioration, frailty and adverse reactions in older people living in aged-care facilities in Australia.
METHODS AND ANALYSIS: The reducing medicine-induced deterioration and adverse reactions trial is a multicentre, open-label randomised controlled trial. Participants will be recruited from 39 facilities in South Australia and Tasmania. Residents will be included if they are using four or more medicines at the time of recruitment, or taking more than one medicine with anticholinergic or sedative properties. The intervention group will receive a pharmacist assessment which occurs every 8 weeks. The pharmacists will liaise with the participants' general practitioners when medicine-induced deterioration is evident or adverse events are considered serious. The primary outcome is a reduction in medicine-induced deterioration from baseline to 6 and 12 months, as measured by change in frailty index. The secondary outcomes are changes in cognition scores, 24-hour movement behaviour, grip strength, weight, percentage robust, pre-frail and frail classification, rate of adverse medicine events, health-related quality of life and health resource use. The statistical analysis will use mixed-models adjusted for baseline to account for repeated outcome measures. A health economic evaluation will be conducted following trial completion using data collected during the trial.
ETHICS AND DISSEMINATION: Ethics approvals have been obtained from the Human Research Ethics Committee of University of South Australia (ID:0000036440) and University of Tasmania (ID:H0017022). A copy of the final report will be provided to the Australian Government Department of Health.
TRIAL REGISTRATION NUMBER: Australian and New Zealand Trials Registry ACTRN12618000766213.

PMID: 32327474 [PubMed - indexed for MEDLINE]

Individual factors increasing complexity of drug treatment-a narrative review.

Eur J Clin Pharmacol. 2020 Jun;76(6):745-754

Authors: Schmidt SJ, Wurmbach VS, Lampert A, Bernard S, HIOPP-6 Consortium, Haefeli WE, Seidling HM, Thürmann PA

Abstract
PURPOSE: Complexity of drug treatment is known to be a risk factor for administration errors and nonadherence promoting higher healthcare costs, hospital admissions and increased mortality. Number of drugs and dose frequency are parameters often used to assess complexity related to the medication regimen. However, factors resulting from complex processes of care or arising from patient characteristics are only sporadically analyzed. Hence, the objective of this review is to give a comprehensive overview of relevant, patient-centered factors influencing complexity of drug treatment.
METHODS: A purposeful literature search was performed in MEDLINE to identify potential complexity factors relating to the prescribed drug (i.e. dosage forms or other product characteristics), the specific medication regimen (i.e. dosage schemes or additional instructions), specific patient characteristics and process characteristics. Factors were included if they were associated to administration errors, nonadherence and related adverse drug events detected in community dwelling adult patients.
RESULTS: Ninety-one influencing factors were identified: fourteen in "dosage forms", five in "product characteristics", twelve in "dosage schemes", nine in "additional instructions", thirty-one in "patient characteristics" and twenty in "process characteristics".
CONCLUSIONS: Although the findings are limited by the non-systematic search process and the heterogeneous results, the search shows the influence of many factors on the complexity of drug treatment. However, to evaluate their relevance for individual patients, prospective studies are necessary.

PMID: 32239242 [PubMed - indexed for MEDLINE]

Estimated dermal exposure to nebulized pharmaceuticals for a simulated home healthcare worker scenario.

J Occup Environ Hyg. 2020 04;17(4):193-205

Authors: Ishau S, Reichard JF, Maier A, Niang M, Yermakov M, Grinshpun SA

Abstract
The duties of home healthcare workers are extensive. One important task that is frequently performed by home healthcare workers is administration of nebulized medications, which may lead to significant dermal exposure. In this simulation study conducted in an aerosol exposure chamber, we administered a surrogate of nebulizer-delivered medications (dispersed sodium chloride, NaCl) to a patient mannequin. We measured the amount of NaCl deposited on the exposed surface of the home healthcare worker mannequin, which represented the exposed skin of a home healthcare worker. Factors such as distance and position of the home healthcare worker, room airflow rate and patient's inspiratory rate were varied to determine their effects on dermal exposure. There was a 2.78% reduction in dermal deposition for every centimeter the home healthcare worker moved away from the patient. Increasing the room's air exchange rate by one air change per hour increased dermal deposition by about 2.93%, possibly due to a decrease in near field particle settling. For every 10-degrees of arc the home healthcare worker is positioned from the left side of the patient toward the right and thus moving into the ventilation airflow direction, dermal deposition increased by about 4.61%. An increase in the patient's inspiratory rate from 15-30 L/min resulted in an average of 14.06% reduction in dermal deposition for the home healthcare worker, reflecting a relative increase in the aerosol fraction inhaled by the patient. The findings of this study elucidate the interactions among factors that contribute to dermal exposure to aerosolized pharmaceuticals administered by home healthcare workers. The results presented in this paper will help develop recommendations on mitigating the health risks related to dermal exposure of home healthcare workers.

PMID: 32134702 [PubMed - indexed for MEDLINE]

Internist (Berl). 2021 Feb 13:1-6. doi: 10.1007/s00108-021-00959-5. Online ahead of print.

ABSTRACT

Less than a year after the first detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccines have been approved for routine use in numerous countries and have already been used in mass vaccination programs. Vaccines include the mRNA BNT162b2 and mRNA 1273. Allergic reactions and anaphylaxis account for a substantial proportion of the adverse reactions to these vaccines observed to date, but overall they are rare. The incidence of anaphylaxis in the context of SARS-CoV‑2 vaccination with the mRNA vaccines appears to be approximately 10-fold higher than with previous vaccines, at approximately 1 per 100,000 vaccine injections. One focus of the present article is a systematic review of the components of mRNA vaccines against " coronavirus disease 2019 " (COVID-19). Differences from established vaccines are addressed and the allergic potential of liposomes, polyethylene glycol, tromethamine/trometamol, and mRNA are discussed. Another focus is on the clinical presentation and course of allergic reactions to the COVID-19 vaccines. This is followed by a discussion of the therapeutic approach to anaphylactic reactions, as well as the drugs and medical supplies required to treat them. It is important to note that any vaccinee may be affected by anaphylaxis, regardless of whether or not allergic diseases are already known. Therefore, every vaccination site and every vaccinator must be prepared to recognize and treat severe allergic reactions.

PMID:33580823 | PMC:PMC7881317 | DOI:10.1007/s00108-021-00959-5

Cancer Immunol Immunother. 2021 Feb 12. doi: 10.1007/s00262-021-02876-w. Online ahead of print.

ABSTRACT

AIM: To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.

MATERIAL AND METHODS: The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways.

RESULTS: Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2-2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8-9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response.

CONCLUSION: In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.

PMID:33580363 | DOI:10.1007/s00262-021-02876-w

Eur J Hosp Pharm. 2021 Feb 12:ejhpharm-2020-002574. doi: 10.1136/ejhpharm-2020-002574. Online ahead of print.

ABSTRACT

BACKGROUND: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia.

METHODS: A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup.

RESULTS: During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002).

CONCLUSIONS: Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality.

PMID:33579720 | DOI:10.1136/ejhpharm-2020-002574

Did we do everything we could have? Nurses' contributions to medicines optimization: A mixed-methods study.

Nurs Open. 2021 Mar;8(2):592-606

Authors: Logan V, Keeley S, Akerman K, De Baetselier E, Dilles T, Griffin N, Matthews L, Van Rompaey B, Jordan S

Abstract
AIM: To explore UK professionals' interpretations of medicines optimization and expansion of nurses' roles.
DESIGN: This mixed-methods study sought professionals' views on nurses' involvement, competency and engagement in monitoring patients for adverse effects of medicines, monitoring adherence, prescribing and patient education.
METHOD: An online survey and interviews were undertaken with nurses, doctors and pharmacists in Wales and England, May 2018 to July 2019.
RESULTS: In all, 220 nurses, 17 doctors and 62 pharmacists responded to the online survey, and 24 professionals were interviewed. Nurses were divided over extending their roles, with 123/220 (55.9%) wishing to extend roles in monitoring patients for possible adverse drug reactions (ADRs), 111/220 (50.5%) in adherence monitoring, 121/220 (55.0%) in prescribing and 122/220 (55.4%) in patient education. The best-qualified nurses were the most willing to increase involvement in monitoring patients for ADRs (aOR 13.00, 1.56-108.01). Interviews revealed that both nurses and doctors assumed the other profession was undertaking this monitoring. Respondents agreed that increasing nurses' involvement in medicines optimization would improve patient care, but expressed reservations about nurses' competencies. Collaboration between nurses and doctors was suboptimal (rated 7/10 at best) and between nurses and pharmacists even more so (6/10 at best).
CONCLUSION: Juxtaposition of datasets identified problems with medicines optimization: although most respondents agreed that increasing nurses' involvement would positively impact practice, their educational preparation was a barrier. Only ~50% of nurses were willing to expand their roles to fill the hiatus in care identified and ensure that at least one profession was taking responsibility for ADR monitoring.
IMPACT: To improve multiprofessional team working and promote patient safety, nurse leaders should ensure patients are monitored for possible ADRs by at least one profession. Initiatives expanding nurses' roles in medicines optimization and prescribing might be best targeted towards the more educated nurses, who have multidisciplinary support.

PMID: 33570308 [PubMed - in process]

First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy volunteers.

ERJ Open Res. 2021 Jan;7(1):

Authors: Mackie A, Rascher J, Schmid M, Endriss V, Brand T, Seibold W

Abstract
Background: Inhibition of the epithelial sodium channel (ENaC) represents a mutation-agnostic therapeutic approach to restore airway surface liquid hydration and mucociliary clearance in patients with cystic fibrosis. BI 1265162 is an inhaled ENaC inhibitor with demonstrated preclinical efficacy.
Methods: Three phase I trials of BI 1265162 in healthy male subjects are presented: NCT03349723 (single-rising-dose trial evaluating safety, tolerability and pharmacokinetics (PK)); NCT03576144 (multiple-rising-dose trial evaluating safety, tolerability and PK); and NCT03907280 (absolute bioavailability trial).
Results: BI 1265162 single doses ≤1200 µg and multiple doses of 600 µg were well tolerated. Adverse events were balanced across treatment groups, were of mainly mild or moderate intensity and resolved by trial-end. One subject discontinued from trial medication on day 7 (asymptomatic hyperkalaemia adverse event; recovered day 8). One subject experienced a serious adverse event (neuropathia vestibularis) leading to hospitalisation and missed one of the four dosing periods. Both events were not considered to be drug-related and subjects recovered. BI 1265162 displayed dose-proportional, time-independent PK; maximum accumulation was 1.6-fold; calculated effective elimination half-life was 3.6-8.7 h over the dose ranges tested. Renal excretion was not a major drug elimination route. Oral and inhaled dosing (±activated oral charcoal) absolute bioavailability was 0.50% and ∼40%, respectively.
Conclusion: BI 1265162 single or multiple doses up to 6.5 days were well tolerated. Systemic exposures mainly represent drug absorbed through the lungs and not the gastrointestinal tract, with ∼40% of the inhaled dose reaching the systemic circulation. Accumulation was minimal. Twice-daily dosing is supported for future development.

PMID: 33569494 [PubMed]

Diclofenac in adolescents: diagnosing and treating gastrointestinal adverse drug reactions can prevent future deaths.

BMJ Evid Based Med. 2021 Feb 10;:

Authors: Thomas ET, Richards GC

PMID: 33568352 [PubMed - as supplied by publisher]

Pharmaceutical marketing-greater than the sum of its parts?

Drug Ther Bull. 2020 Oct;58(10):147-149

Authors: Wilcock M

PMID: 32826309 [PubMed - indexed for MEDLINE]