Medication Safety in Older Adults: Learning From 2020 as We Launch into 2021.

J Gerontol Nurs. 2021 Jan 01;47(1):7-11

Authors: Brandt NJ, Lee M

Abstract
In health care, the year 2020 is marked by the ongoing coronavirus (COVID-19) pandemic, with much research published to clarify infection risk, treatment approaches, and proposed interventions to reduce spread and combat complications. Although much work focused on COVID-19, medication safety remains a priority, and studies on adverse drug reactions, high-risk medications, and approaches to mitigate risk associated with chronic medication use, such as inappropriate dosing in hospital settings, were published. A continued commitment to patient-centered care, such as the approach put forth by the Age-Friendly Health Systems initiative and telehealth initiatives, ensures that even as health care practice strives to meet the challenge of an unprecedented global pandemic, safe medication use informed by patient needs continues to guide best practices through lessons learned. [Journal of Gerontological Nursing, 47(1), 7-11.].

PMID: 33377979 [PubMed - indexed for MEDLINE]

The association between age and adverse events due to biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: A retrospective cohort study.

Medicine (Baltimore). 2020 Dec 24;99(52):e23861

Authors: Ikari Y, Yajima N, Miwa Y

Abstract
ABSTRACT: We examined whether the age of patients with rheumatoid arthritis was associated with adverse events (AEs) caused by biologic disease-modifying antirheumatic drugs (bDMARDs).Patients with rheumatoid arthritis using bDMARDs from Showa University Hospital, Showa University Northern Yokohama Hospital, and Showa University Koto Toyosu Hospital from January 2005 to December 2017 were eligible for this retrospective cohort study. The maximum observation period was determined to be 1 year. Outcomes in patients older and younger than 75 years were compared. The primary outcome was the rate of drug discontinuation because of AEs caused by bDMARDs. Univariate and multivariate analyses were performed using Pearson's chi-squared test and logistic regression analysis, respectively.A total of 416 patients were enrolled; median (interquartile range [IQR]): 60.0 (44.3 - 71.0) years and 84.6% women; patients ≥ 75 years were 67/416 (16.1%). The rates of drug discontinuation because of AEs caused by bDMARDs were 10.5% (7/67) in patients 75 years and older and 10.9% (38/349) in those younger than 75 years (relative risk 0.95, 95% confidential interval 0.45-2.24). In logistic regression analysis adjusted for covariates, the rate of drug discontinuation showed no significant difference between the patients ≥ 75 years and the those < 75 years (adjusted odds ratio 0.70, 95% confidential interval 0.29-1.75, P = .45).The rate of drug discontinuation because of AEs caused by bDMARDs was not significantly different between patients 75 years and older and patients younger than 75 years.

PMID: 33350780 [PubMed - indexed for MEDLINE]

Incidence of acute spinal cord injury and associated complications of methylprednisolone therapy: a national population-based study in South Korea.

Spinal Cord. 2020 Feb;58(2):232-237

Authors: Choi SH, Sung CH, Heo DR, Jeong SY, Kang CN

Abstract
STUDY DESIGN: Retrospective population-based cohort study OBJECTIVES: To evaluate the incidence of acute spinal cord injury (SCI) in South Korea, and the prescription rates and complications related to high dose methylprednisolone therapy.
SETTING: Health Insurance Review and Assessment Service (HIRA) data METHODS: National database of the Korean HIRA between 2007 and 2017 was reviewed. To identify patients with acute SCI and the use of high dose methylprednisolone, International Classification of Disease revision codes, medical behavior codes and examination codes were used. Patients were grouped according to whether or not they received methylprednisolone therapy (MP group vs non-MP group).
RESULTS: The average age-adjusted incidence of acute SCI per 1,000,000 persons was 26.4 and the peak incidence was in the 50s overall. The methylprednisolone prescription rate was highest in 2012 (76%) and continued to decrease thereafter, being lowest in 2017 (41%). The MP group showed higher complication rates in terms of pneumonia (OR 1.8, 95% CI, 1.62-2.0), GI bleeding (OR 1.2, 95% CI, 1.05-1.38), and UTI (OR 1.68, 95% CI, 1.53-1.84). The average length of hospitalization was longer in patients who received methylprednisolone (26.5 days vs. 24.4 days, p < 0.05).
CONCLUSIONS: The average age-adjusted incidence of acute SCI for 11 years was 26.4 per 1,000,000 persons and highest in 50s. Strategies should be established, and national health resources should be allocated to prevent acute SCI from occurring in older people. The prescription rate of high dose methylprednisolone for acute SCI is decreasing in South Korea but it is still high.

PMID: 31527724 [PubMed - indexed for MEDLINE]

Spinal and paraspinal inflammatory reactions after epidural steroid injection in a patient taking disease-modifying antirheumatic drugs.

Reg Anesth Pain Med. 2020 Dec 21;:

Authors: Patel PM, Lam I, Liu BP, Benzon HT

Abstract
BackgroundDisease-modifying anti-rheumatic drugs (DMARDs) are used in the management of rheumatoid arthritis (RA) and are classified as conventional DMARDs and biologic agents. A concern with DMARDs is the increased risk of infection after surgery. A practice advisory from the American Society of Anesthesiologists recommend alternatives to neuraxial injections in patients who are immunocompromized. We describe a patient who was on several DMARDs and developed inflammatory reactions in her bilateral paraspinal muscles and lumbar spine after an epidural steroid injection (ESI). CASE PRESENTATION: The patient was a 79-year-old woman; she was taking methotrexate, adalimumab and prednisone for her RA. She had a left L5-S1 paramedian ESI for her L5 radiculitis. After relief of her back and radicular pain for 5 weeks, she had an acute exacerbation of her back pain. MRI showed bilateral paraspinal fluid accumulations and enhancement in her ligamentum flavum. Cultures of the aspirated fluid and biopsy specimens were negative for fungal, aerobic and anaerobic organisms. A repeat MRI 2 months later showed diminution of the fluid collection but with a new fluid accumulation near the left L4-5 facet and left L4 pedicle. Repeat cultures and gram stain of the specimens taken from the pedicle and the paraspinal muscles were negative. The patient was followed by her rheumatologist and in the pain clinic until resolution of her symptoms. CONCLUSIONS: Several society guidelines recommend the continuation of methotrexate but stoppage of the biologic DMARDS before surgery. The occurrence of an intense inflammatory reaction after an ESI in our patient calls for additional research on the subject and shared decision-making between the pain physician, patient and rheumatologist especially in patients on several DMARDs.

PMID: 33443168 [PubMed - as supplied by publisher]

Level of adherence and associated factors among HIV-positive adolescents on antiretroviral therapy in Cameroon.

Afr J AIDS Res. 2020 Dec;19(4):269-275

Authors: Bongfen MC, Torpey K, Ganle J, Ankomah A

Abstract
Aim: Globally, there were over 250 000 new HIV infections among adolescents in 2017, with a higher proportion of these in sub-Saharan Africa. In Cameroon, UNICEF estimated over 4 200 new HIV infections in adolescents in 2015; by 2016, there were over 40 000 adolescents who had HIV. Given that the number of adolescents living with HIV in Cameroon is on the increase, there is a need to better understand the factors influencing adherence to treatment. The objective of this study was to assess the factors associated with adherence among adolescents in Cameroon. Methods: A cross-sectional study was conducted. A total of 460 HIV+ adolescents who were receiving antiretroviral therapy were sampled randomly from nine health facilities. Questionnaires and data extraction forms were used to collect data. Descriptive (frequencies and proportions) and inferential (chi-square and multivariate logistic regression) statistical analyses methods were used to analyse the data. Statistical significance was set at p = 0.05 and 95% confidence level. Results: The level of adherence to antiretroviral therapy among the adolescents was 83%. Twelve out of 30 independent variables examined showed significant statistical association with adherence at the bivariate level. In the multivariable logistic regression analyses, however, only two variables significantly predicted adherence - experiencing side effects (AOR = 2.63; 95% CI = 1.14, 6.09; p = 0.02), and internalized stigma (AOR = 2.51; 95% CI = 1.04, 6.04; p = 0.04). Conclusion: Adherence to treatment among adolescents in Cameroon was found to be suboptimal. There is a need for more individualized, targeted medication counselling for adolescents and their guardians as well as strategies to reduce internalized stigma and improve adherence to antiretroviral treatment.

PMID: 33337976 [PubMed - indexed for MEDLINE]

[Drug interactions in dermatological systemic treatment].

Hautarzt. 2021 Jan;72(1):44-49

Authors: Krause K, Jahn K, Homey B

Abstract
Severe pharmacological side effects have an occurrence of 5-7% and represent a frequent reason for hospital admission. The prevalence of undesired pharmacological side effects during hospitalization is even higher with approximately 11.5%. The causes are often interactions between drugs due to the polypharmacy of multimorbid older patients. On average, a 65-year-old male patient will simultaneously be taking 5 medications. Due to the increasing use of systemic drugs in dermatology and the simultaneously increasing polypharmacy, knowledge of interactions between medications is essential for dermatologists in order to avoid severe side effects of drugs. This article provides assistance in order to identify patients and medications with a high risk for severe interactions and, therefore, to avoid the occurrence of undesired effects or the reduction of the therapeutic effects of active substances. We would like to point out that this article deals with individual aspects and does not mean that the testing of individual drug interactions with interaction programs can be omitted. It should also not be neglected that in addition to prescription-only drugs, foodstuffs, dietary supplements and herbs can also lead to interactions with medications.

PMID: 33242135 [PubMed - indexed for MEDLINE]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2021/01/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Bioequivalence study of two perindopril tert-butylamine tablet formulations in healthy Chinese subjects under fasting and fed conditions: A randomized, open-label, single-dose, crossover trial.

Biomed Pharmacother. 2021 Jan 08;135:111221

Authors: Li Q, Hao Z, Yu Y, Tang Y

Abstract
BACKGROUND: To evaluate the bioequivalence between test and reference formulations of perindopril tert-butylamine under fasting and fed conditions and to assess their pharmacokinetic (PK) and safety profiles.
METHOD: A randomized, open-label, single-dose, crossover trial was conducted in healthy Chinese subjects. Test or reference perindopril tert-butylamine tablets (4 mg) were randomly given to subjects under fasting (2-period crossover, with an administration sequence of test tablet (T), reference tablet (R) or RT) and fed (4-period crossover, with an administration sequence of TRTR or RTRT) conditions, while each single administration was followed by a 14-day washout period. The plasma concentrations and corresponding non-compartmental PK parameters of perindopril and perindoprilat were determined. The two formulations were considered to be bioequivalent if the 90 % confidence intervals (CIs) of the geometric mean (GM) ratio (test/reference) for Cmax, AUC0-t, and AUC0-∞ (perindopril) was both within the range of 80-125 %. Safety assessments including vital signs, physical examination, laboratory examination, 12-lead ECG and reports of treatment emergent adverse events (TEAEs) were carefully documented.
RESULTS: A total of 64 subjects (32 in each trial) were randomized and all completed the trials. Regardless of fasting or fed trials, the PK characteristics of perindopril and perindoprilat for the test formulation were similar to those of the reference formulation (all P > 0.05). The 90 % CIs of the geometric mean (GM) ratio for Cmax, AUC0-t, and AUC0-∞, respectively, were 92.86-106.81 %, 98.44-102.88 % and 98.48-103.02 % under the fasting condition and 90.64-110.04 %, 96.95-101.90 % and 96.83-101.78 % under the fed condition, which were both within the pre-specified range of 80-125 %. A total of 10 (31.3 %) fasted subjects and 11 (34.4 %) fed subjects experienced 11 and 24 TEAEs, respectively, all of which were within the severity of grade 1. The incidence of TEAEs and drug-related TEAEs were similar between test and reference formulations (all P > 0.05) and no serious TEAEs or deaths occurred during the trials.
CONCLUSIONS: The test and reference formulations of perindopril tert-butylamine tablets (4 mg) were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions.

PMID: 33433351 [PubMed - as supplied by publisher]

Communicating tailored risk information of cancer treatment side effects: Only words or also numbers?

BMC Med Inform Decis Mak. 2020 10 27;20(1):277

Authors: Vromans RD, Pauws SC, Bol N, van de Poll-Franse LV, Krahmer EJ

Abstract
BACKGROUND: The increased availability of patient reported outcome data makes it feasible to provide patients tailored risk information of cancer treatment side effects. However, it is unclear how such information influences patients' risk interpretations compared to generic population-based risks, and which message format should be used to communicate such individualized statistics.
METHODS: A web-based experiment was conducted in which participants (n = 141) read a hypothetical treatment decision-making scenario about four side effect risks of adjuvant chemotherapy for advanced colon cancer. Participants were cancer patients or survivors who were recruited from an online Dutch cancer patient panel. All participants received two tailored risks (of which the reference class was based on their age, gender and tumor stage) and two generic risks conveying the likelihood of experiencing the side effects. The risks were presented either in words-only ('common' and 'very common'), or in a combination of words and corresponding numerical estimates ('common, 10 out of 100' and 'very common, 40 out of 100'). Participants' estimation of the probability, accuracy of their estimation, and perceived likelihood of occurrence were primary outcomes. Perceived personal relevance and perceived uncertainty were secondary outcomes.
RESULTS: Tailored risks were estimated as higher and less accurate than generic risks, but only when they were presented in words; Such differences were not found in the verbal and numerical combined condition. Although tailoring risks did not impact participants' perceived likelihood of occurrence, tailored risks were perceived as more personally relevant than generic risks in both message formats. Finally, tailored risks were perceived as less uncertain than generic risks, but only in the verbal-only condition.
CONCLUSIONS: Considering current interest in the use of personalized decision aids for improving shared decision-making in oncology, it is important that clinicians consider how tailored risks of treatment side effects should be communicated to patients. We recommend both clinicians who communicate probability information during consultations, and decision aid developers, that verbal descriptors of tailored risks should be supported by numerical estimates of risks levels, to avoid overestimation of risks.

PMID: 33109175 [PubMed - indexed for MEDLINE]

Prevalence and significance of potential drug-drug interactions among cancer patients receiving chemotherapy.

BMC Cancer. 2020 Apr 19;20(1):335

Authors: Ismail M, Khan S, Khan F, Noor S, Sajid H, Yar S, Rasheed I

Abstract
BACKGROUND: Cancer patients often receive multiple drugs to maximize their therapeutic benefit, treat co-morbidities and counter the adverse effects of chemotherapy. Concomitant administration of multiple drugs increases the risk of drug interactions leading to compromised therapeutic efficacy or safety of therapy. The purpose of this study was to identify the prevalence, levels and predictors of potential drug-drug interactions (pDDIs) among cancer patients.
METHODS: Six hundred and 78 patients receiving chemotherapy from two tertiary care hospitals were included in this cross-sectional study. Patient medication profiles were screened for pDDIs using the Micromedex® database. Logistic regression analysis was performed to identify the predictors of pDDIs.
RESULTS: The overall prevalence of pDDIs was 78%, majority of patients had 1-2 pDDIs (39.2%). A total of 1843 pDDIs were detected. Major-pDDIs were most frequent (67.3%) whereas, a significant association of pDDIs was found between > 7 all prescribed drugs (p < 0.001) and ≥ 3 anti-cancer drugs (p < 0.001). Potential adverse outcomes of these interactions include reduced therapeutic effectiveness, QT interval prolongation, tendon rupture, bone marrow suppression and neurotoxicity.
CONCLUSIONS: Major finding of this study is the high prevalence of pDDIs signifying the need of strict patient monitoring for pDDIs among cancer patients. Patients at higher risk to pDDIs include those prescribed with > 7 any types of drugs or ≥ 3 anticancer drugs. Moreover, list of most frequently identified major and moderate interactions will aid health care professional in timely identification and prevention of pDDIs.

PMID: 32307008 [PubMed - indexed for MEDLINE]

The value of organs-on-chip for regulatory safety assessment.

ALTEX. 2020;37(2):208-222

Authors: Heringa MB, Park MVDZ, Kienhuis AS, Vandebriel RJ

Abstract
Organs-on-chip (OC) have gained much interest as animal-free toxicity testing methods due to their closer resemblance to human tissues and longer culture viability than conventional in vitro methods. The current paper discusses where and how OCs may take a role in the transition to a more predictive, animal-free safety assessment for regulatory purposes. From a preliminary analysis of a repeated dose toxicity database, ten organs of priority for OC development for regu­latory use have been identified. For a number of these organs (lung, skin, liver, kidney, heart, and intestine), OCs are already at rather advanced stages of development, such that involvement of regulators becomes of value in the optimi­zation towards fitness-for-purpose of these methods. For organs such as testis, spleen, brain, and stomach, OCs are much more premature, if existing at all. Therefore, developmental work on OCs for these latter organs is expected to stay in the academic arena for the coming time. A number of technical recommendations and some challenges to reaching final implementation are discussed. We recommend that the development of OCs goes forward together with the development of adverse outcome pathways (AOP) and that they are combined with other methods into integrated testing strategies. Overall, opportunities exist, but much still needs to be done. In our view, regular interactions in multi-stakeholder work­shops on the application of animal-free innovations such as OCs will be beneficial.

PMID: 31841612 [PubMed - indexed for MEDLINE]

[Potentially inappropriate medication in a German practice network-who prescribes what to whom?]

Z Gerontol Geriatr. 2020 Nov;53(7):647-654

Authors: Gudd K, Meier F, Lindenthal J, Wambach V, Schöffski O

Abstract
BACKGROUND: Potentially inappropriate medication (PIM) carries the risk of increased drug side effects for older people. The prevalence data are known but no descriptive analyses of prescription behavior as a starting point for reducing PIM have yet been conducted.
OBJECTIVE: The aim of the study was to analyze PIM prescription in the outpatient sector and to identify risk groups where increased awareness of the issue is needed.
MATERIAL AND METHODS: The basis for the investigation was the data set of the AOK Bavaria health insurance, which contains anonymized prescription data of a practice network for patients aged 65 years and older from 2010 to 2014. The Priscus list was used to identify the PIM.
RESULTS: There were 410,934 prescriptions during the investigation period. The prevalence of PIM was 5.60%. Family doctors prescribed 5.39% PIM and specialists for neurology, psychiatry and psychotherapy (NPP) prescribed 16.36% PIM. Regardless of the medical discipline, PIM from the drug groups psycholeptics, psychoanaleptics and antihypertensive drugs were most frequently prescribed. For men and women PIM accounted for 4.50% and 6.31%, respectively, of the prescriptions during the period. In terms of age groups older women received PIM most frequently.
CONCLUSION: In the case of specialists for NPP a high prevalence of prescriptions for PIM could be established; however, in absolute terms family doctors prescribed significantly more PIM overall. This mainly affected women and especially those between 80 and 84 years old. In the future family doctors should be made more aware with respect to the prescription of psychopharmaceuticals and antihypertensive drugs to older women.

PMID: 31773247 [PubMed - indexed for MEDLINE]

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2021/01/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2021/01/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The 48-week Safety and Therapeutic Effects of Tenofovir Alafenamide in HBV Related Acute-on-chronic Liver Failure: A Prospective Cohort Study.

J Viral Hepat. 2021 Jan 10;:

Authors: Zhang Y, Xu W, Zhu X, Li X, Li J, Shu X, Lai J, Xie J, Xie C, Peng L

Abstract
Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients.Eighty-eight eligible subjects were included and divided into three groups: TAF group, TDF group, and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow-up. No drug-related adverse events were observed within a 48-week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% ,59.5% (P = 0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, P = 0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were -0.7 (IQR -3.0,13.0) vs. 15.0 (IQR -3.0,21.0) vs. 5.0 (IQR -9.0,14.0), respectively (P = 0.334), while the median changes of eGFR were -2.12 (IQR -13.87,1.44) vs. -10.43(IQR -20.21,3.18) vs. -5.31 (IQR -14.72,5.44) mL/min/1.73m2 , respectively (P = 0.592). In this real-world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy.

PMID: 33423348 [PubMed - as supplied by publisher]

Usefulness of atosiban for tocolysis during external cephalic version: Systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol. 2020 Dec 31;258:86-92

Authors: Riemma G, Schiattarella A, La Verde M, Cianci S, Savoia F, De Franciscis P, Cobellis L, Colacurci N, Morlando M

Abstract
INTRODUCTION: Breech/transverse presentation is responsible for about 30-50 % of cesarean sections in the world. Cesarean section carries a five-fold greater morbidity than vaginal delivery, deeply impacting on women's health. External Cephalic Version (ECV) is an external manipulation used to convert a non-cephalic to a cephalic presentation. The use of tocolysis might facilitate this procedure; however, it is still controversial which drug should be considered as first choice.
OBJECTIVE: To assess the effectiveness of tocolysis with atosiban, a competitive oxytocin receptor antagonist, in order to increase the rate of successful ECV.
STUDY DESIGN: Nine databases (including MEDLINE, CINAHL, LILACS, EMBASE, Scopus, ClinicalTrials.gov, Scielo, PROSPERO, Cochrane at CENTRAL) were searched from the inception to August 2020 using a combination of MeSH terms and keywords regarding "atosiban" and "external cephalic version". We included trials of women with a singleton pregnancy who reached at least 36 weeks of gestation and were scheduled to ECV and tocolysis with atosiban (intervention group) compared to beta-agonists or other drugs (control group). The primary outcome was the incidence of successful ECV. Summary measures were reported as relative risk (RR) with 95 % confidence interval (CI).
DATA COLLECTION AND ANALYSIS: Four studies (1534 women) were eligible for analysis. ECV success rate was significantly lower in women randomized to atosiban (36.7 % vs 45.3 %; RR 0.78 [95 % CI 0.6 to 0.98]). Cesarean section and vaginal delivery rates did not differ between intervention and control group ((59.8 % vs 52.6 %; RR 1.17 [0.98-1.38] and (38.6 % vs 45.0 %; RR 0.83 [95 % CI 0.69-1.01] respectively). Cephalic (36.9 % vs 44.6 %; RR 0.81 [95 % CI 0.65 to 1.01], or breech/transverse presentation at labor (63.4 % vs 55.1 %; RR 1.18 [95 % CI 0.99-1.40]), APGAR score less than 7 at 5 min (1.6 % vs 2.0 %; RR 1.14 [95 % CI 0.27-4.73], NICU admissions (44.2 % vs 48.1 %; RR 0.92 [95 % CI 0.58-1.46] and Umbilical cord pH were similar in both groups. Drug-related side effects were lower in women randomized to atosiban, compared with control group (16.0 % vs 42.9 %; RR 0.38 [95 % CI 0.31 to 0.47].
CONCLUSION: The use of atosiban for tocolysis does not improve the rate of successful ECVs when compared to beta-agonists. However, atosiban was associated with a significantly lower incidence of side effects and comparable cesarean section rates.

PMID: 33421816 [PubMed - as supplied by publisher]

A phase 1b trial of selinexor, a first-in-class selective inhibitor of nuclear export (SINE), in combination with doxorubicin in patients with advanced soft tissue sarcomas (STS).

Eur J Cancer. 2021 Jan 05;144:360-367

Authors: Lewin J, Malone E, Al-Ezzi E, Fasih S, Pedersen P, Accardi S, Gupta A, Abdul Razak A

Abstract
BACKGROUND: Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) compound with single-agent activity in soft tissue sarcoma (STS). The study's aim was to determine the safety and efficacy of selinexor in combination with doxorubicin in patients with locally advanced/metastatic STS.
METHODS: This phase 1b study used a mTPI design. Patients received selinexor at either 60 or 80 mg weekly PO plus doxorubicin (75 mg/m2 IV q21 days). Patients with clinical benefit (defined as ≥stable disease via RECIST 1.1) after six cycles of combination treatment received maintenance selinexor until disease progression or unacceptable toxicity. Disease assessments were conducted every two cycles. Pharmacokinetic data were collected on the first three patients per dose level.
RESULTS: Twenty-five patients were enrolled (20 female, ECOG 0/1: 13/12, median age 57 years [range 21-74]). Disease subtypes included leiomyosarcoma (n = 6), malignant peripheral nerve sheath tumour (n = 3) and other sarcomas (n = 16). Three (12%) and 22 (88%) patients were treated at 60 mg and 80 mg of selinexor, respectively. The most common ≥G3 drug-related adverse events (AEs) were haematological, including neutropenia (56%), febrile neutropenia (28%) and anaemia (24%). There were four dose-limiting toxicities (febrile neutropenia (x2), vomiting, fatigue) all at the 80 mg dose level. There was one death secondary to heart failure. Of the 24 evaluable patients, 5 (21%) had a partial response and 15 (63%) had SD as best response. The estimated median progression-free survival (PFS) and overall survival (OS) were 5.5 (95% CI:4.1-5.7) and 10.5 (95% CI:7.5-14) months.
CONCLUSION: In a heterogeneous group of patients with locally advanced/metastatic STS, the combination of selinexor and doxorubicin fulfilled the prespecified boundary for tolerability.

PMID: 33418486 [PubMed - as supplied by publisher]

[Drug-induced interstitial lung diseases].

Pathologe. 2021 Jan 07;:

Authors: Bittmann I

Abstract
Pulmonary drug reactions are a relatively common factor causing interstitial pulmonary disease. Histological findings of pulmonary drug reactions can mimic other conditions such as various forms of idiopathic interstitial pneumonia such as nonspecific interstitial pneumonia, organizing pneumonia, diffuse alveolar damage, or usual interstitial pneumonia. The correct diagnosis is important since a causal therapy is possible by stopping the administration. A stringent correlation between dose/time of administration and the type of reaction exists for only a few drugs. An increased risk of drug side effects can arise from known reactions to that specific drug, the patient's history, the type of underlying disease, genetic polymorphisms, occupational factors, and interactions with other drugs. The identification of a pulmonary drug reaction is a difficult task that can often only be solved in an interdisciplinary manner, for which in rare cases a lung biopsy is necessary. Pathology then has to identify histomorphological reaction patterns to exclude other causes and correlate findings with clinical data. In most cases, however, the diagnosis of a drug reaction will be by exclusion.

PMID: 33415347 [PubMed - as supplied by publisher]

Apnoeic oxygenation for emergency anaesthesia of pre-hospital trauma patients.

Scand J Trauma Resusc Emerg Med. 2021 Jan 07;29(1):10

Authors: Crewdson K, Heywoth A, Rehn M, Sadek S, Lockey D

Abstract
BACKGROUND: Efficient and timely airway management is universally recognised as a priority for major trauma patients, a proportion of whom require emergency intubation in the pre-hospital setting. Adverse events occur more commonly in emergency airway management, and hypoxia is relatively frequent. The aim of this study was to establish whether passive apnoeic oxygenation was effective in reducing the incidence of desaturation during pre-hospital emergency anaesthesia.
METHODS: A prospective before-after study was performed to compare patients receiving standard care and those receiving additional oxygen via nasal prongs. The primary endpoint was median oxygen saturation in the peri-rapid sequence induction period, (2 minutes pre-intubation to 2 minutes post-intubation) for all patients. Secondary endpoints included the incidence of hypoxia in predetermined subgroups.
RESULTS: Of 725 patients included; 188 patients received standard treatment and 537 received the intervention. The overall incidence of hypoxia (first recorded SpO2 < 90%) was 16.7%; 10.9% had SpO2 < 85%. 98/725 patients (13.5%) were hypoxic post-intubation (final SpO2 < 90% 10 minutes post-intubation). Median SpO2 was 100% vs. 99% for the standard vs. intervention group. There was a statistically significant benefit from apnoeic oxygenation in reducing the frequency of peri-intubation hypoxia (SpO2 < =90%) for patients with initial SpO2 > 95%, p = 0.0001. The other significant benefit was observed in the recovery phase for patients with severe hypoxia prior to intubation.
CONCLUSION: Apnoeic oxygenation did not influence peri-intubation oxygen saturations, but it did reduce the frequency and duration of hypoxia in the post-intubation period. Given that apnoeic oxygenation is a simple low-cost intervention with a low complication rate, and that hypoxia can be detrimental to outcome, application of nasal cannulas during the drug-induced phase of emergency intubation may benefit a subset of patients undergoing emergency anaesthesia.

PMID: 33413576 [PubMed - in process]

Health professionals perception and beliefs about drug- related problems on polymedicated older adults- a focus group study.

BMC Geriatr. 2021 Jan 07;21(1):27

Authors: Plácido AI, Herdeiro MT, Simões JL, Amaral O, Figueiras A, Roque F

Abstract
BACKGROUND: Polymedicated older patients are at greater risk of suffering from adverse events. For this reason, the detection of both inappropriate polypharmacy and polypharmacy-associated Drug-Related Problems (DRPs) are essential to improve the health and wellbeing of older adults and to reduce healthcare costs. This work aims to explore health professionals' perceptions and opinions about polypharmacy and the handling of medicines by polymedicated older adults.
METHODS: Thirteen focus groups with 94 health professionals (20 community pharmacists, 40 general practitioners and, 34 nurses) were conducted in primary healthcare centers of the center region of Portugal. Participants were asked to discuss their perceptions and beliefs concerning DRPs in polymedicated older adults. The sessions were audiotaped. After the transcription and coding of focus group sessions, a thematic analysis was done.
RESULTS: The following four main themes emerged from the 13 focus group sessions: poor compliance and polypharmacy- A perpetuated vicious cycle, organization of the healthcare system, interaction and communication between the health professionals, and strategies to prevent inappropriate polypharmacy.
CONCLUSIONS: The lack of both an efficient network of information and Interaction and communication between Health professionals makes the detection and/ or prevention of polypharmacy in older adults difficult. The implementation of new models to manage and/or prevent polypharmacy based on health professional perception and beliefs is essential to prevent DRPs and improve compliance among older adults.

PMID: 33413137 [PubMed - in process]