Big Data in the Assessment of Pediatric Medication Safety.

Pediatrics. 2020 02;145(2):

Authors: McMahon AW, Cooper WO, Brown JS, Carleton B, Doshi-Velez F, Kohane I, Goldman JL, Hoffman MA, Kamaleswaran R, Sakiyama M, Sekine S, Sturkenboom MCJM, Turner MA, Califf RM

Abstract
Big data (BD) in pediatric medication safety research provides many opportunities to improve the safety and health of children. The number of pediatric medication and device trials has increased in part because of the past 20 years of US legislation requiring and incentivizing study of the effects of medical products in children (Food and Drug Administration Modernization Act of 1997, Pediatric Rule in 1998, Best Pharmaceuticals for Children Act of 2002, and Pediatric Research Equity Act of 2003). There are some limitations of traditional approaches to studying medication safety in children. Randomized clinical trials within the regulatory context may not enroll patients who are representative of the general pediatric population, provide the power to detect rare safety signals, or provide long-term safety data. BD sources may have these capabilities. In recent years, medical records have become digitized, and cell phones and personal devices have proliferated. In this process, the field of biomedical science has progressively used BD from those records coupled with other data sources, both digital and traditional. Additionally, large distributed databases that include pediatric-specific outcome variables are available. A workshop entitled "Advancing the Development of Pediatric Therapeutics: Application of 'Big Data' to Pediatric Safety Studies" held September 18 to 19, 2017, in Silver Spring, Maryland, formed the basis of many of the ideas outlined in this article, which are intended to identify key examples, critical issues, and future directions in this early phase of an anticipated dramatic change in the availability and use of BD.

PMID: 31937606 [PubMed - indexed for MEDLINE]

[Pharmacologic treatment of heart failure with reduced ejection fraction in chronic kidney disease].

Dtsch Med Wochenschr. 2019 12;144(24):1714-1720

Authors: Heine GH, Rogacev KS

Abstract
Medical management of patients with co-existing Heart Failure with reduced Ejection Fraction (HFrEF) and chronic kidney disease (CKD) poses a significant challenge to treating physicians. On the one hand, the traditional therapeutic strategies such as betablockers, angiotensin converting enzyme inhibiotors, angiotensin receptor blockers and mineralocorticoid receptor antagonists have been evaluated in clinical trials that broadly excluded patients with significant CKD. On the other hand, inhibition of the renin angiotensin aldosterone system can lead to worsening of renal function and hyperkalemia potentially causing harm. Consequently, the cornerstones of heart failure treatment are often not adequately employed in HFrEF patients with CKD, a fact which is in itself a risk factor for worse outcomes in this patient population. Notably, it has been shown that these established pharmacologic strategies can be safely administered when carefully monitored. Iron treatment in anemia in CKD is well established and outcome trials in HFrEF are underway. New therapeutic strategies are under current investigation. Sodium glucose transporter 2 inhibitors show promising results in HFrEF and in CKD trials. In addition, Sacubitril/Valsartan significantly reduced events in HFrEF and might reduce renal events in HFpEF.

PMID: 31791077 [PubMed - indexed for MEDLINE]

[Toxicity of quinolone antibiotics - new untoward effects and reevaluation of known side effects].

Dtsch Med Wochenschr. 2019 12;144(24):1697-1702

Authors: Kern WV

Abstract
Quinolones have recently been reevaluated based on new possible side effects and new risk assessments of known side effects. Several of the recently reported untoward effects are not new to the class, and they are very rare compared with the relatively common neuropsychiatric adverse events. New associations are aortic aneurysm/dissection and long-standing peripheral neuropathy, muscle weakness, mobility and gait disorders with unclear causal relationship to fluoroquinolone treatment and no known effective therapeutic interventions. Based on estimates from comparative data there could be slightly more than 1000 additional cases of adverse drug effects associated with fluoroquinolone treatment versus other common antibiotics per 100 000 treatment episodes - most of them being neuropsychiatric side effects in primary care, tendinopathy and - more rarely and uncertain - liver toxicity. Consequences were safety alerts in the USA and in European countries with recommendations that the use of the marketed fluoroquinolone antibiotics should be restricted and other antibacterial medicines be preferred if possible. The prophylactic use should be abandoned (travellers' diarrhea and prevention of relapsing cystitis) or critically reevaluated and individualized (prevention of neutropenic fever and of spontaneous bacterial peritonitis).

PMID: 31791074 [PubMed - indexed for MEDLINE]

New therapeutic perspectives to manage refractory immune checkpoint-related toxicities.

Lancet Oncol. 2019 01;20(1):e54-e64

Authors: Martins F, Sykiotis GP, Maillard M, Fraga M, Ribi C, Kuntzer T, Michielin O, Peters S, Coukos G, Spertini F, Thompson JA, Obeid M

Abstract
Immune checkpoint inhibitors are reshaping the prognosis of many cancer and are progressively becoming the standard of care in the treatment of many tumour types. Immunotherapy is bringing new hope to patients, but also a whole new spectrum of toxicities for healthcare practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of patients with cancer are increasingly confronted with the therapeutic challenge of treating patients with severe and refractory immune-related adverse events. In this Personal View, we summarise the therapeutic strategies that have been used to manage such toxicities resulting from immune checkpoint inhibitor treatment. On the basis of current knowledge about their pathogenesis, we discuss the use of new biological and non-biological immunosuppressive drugs to treat severe and steroid refractory immune-related adverse events. Depending on the immune infiltrate type that is predominant, we propose a treatment algorithm for personalised management that goes beyond typical corticosteroid use. We propose a so-called shut-off strategy that aims at inhibiting key inflammatory components involved in the pathophysiological processes of immune-related adverse events, and limits potential adverse effects of drug immunosuppression on tumour response. This approach develops on current guidelines and challenges the step-by-step increase approach to drug immunosuppression.

PMID: 30614479 [PubMed - indexed for MEDLINE]

Exploring and comparing adverse events between PARP inhibitors.

Lancet Oncol. 2019 01;20(1):e15-e28

Authors: LaFargue CJ, Dal Molin GZ, Sood AK, Coleman RL

Abstract
Ovarian cancer remains one of the most challenging malignancies to treat. Targeted therapies such as poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as one of the most exciting new treatments for ovarian cancer, particularly in women with BRCA1 or BRCA2 mutations or those without a functional homologous recombination repair pathway. Perhaps the most advantageous characteristic of PARP inhibitors is their mechanism of action, which targets cancer cells on the basis of their inherent deficiencies while seemingly avoiding normally functioning cells. Although health-care providers might assume a low toxicity profile because of their specific mechanism of action, PARP inhibitors are not completely benign and overall show a class effect adverse-event profile. Further complicating this situation, three different PARP inhibitors have been approved by the US Food and Drug Administration since 2014, each with their own specific indications and individual toxicity profiles. The diversity of adverse events seen both within and across this class of drug underscores the importance of having a comprehensive reference to help guide clinical decision making when treating patients. This Review characterises and compares all toxicities associated with each PARP inhibitor, both in monotherapy and in novel combinations with other drugs, with a particular focus on potential management strategies to help mitigate toxic effects. Although the excitement surrounding PARP inhibitors might certainly be warranted, a thorough understanding of all associated toxicities is imperative to ensure that patients can achieve maximal clinical benefit.

PMID: 30614472 [PubMed - indexed for MEDLINE]

[Initiation of pharmacotherapy as a risk factor for older patients.]

Adv Gerontol. 2019;32(5):781-786

Authors: Ilina ES, Bogova OT, Gorbatenko SV, Golovina OV, Shalygin VA, Ivashchenko DV, Sinitsina II, Savelieva MI, Potapov VN, Goncharova OV, Puzin SN, Sychev DA

Abstract
The article presents the literature and original data on the problems of falls in elderly patients. The connection of the fact of falling with initiation of therapy by a number of drugs known to have a negative impact on the risk of falling is considered. The article presents data on the frequency and structure of falls on the example of patients with cardiovascular diseases older than 75 years, treated in a multidisciplinary hospital. The analysis of the data showed a tendency of prevalence of the fact of falling in 1/3 patients (33,8%) in the first 5 days of hospital stay, which may be associated with high drug burden and the appointment of «new» drugs for the patient. The study noted that it was on the first day that the selection of therapy took place and additional drugs were often prescribed, leading to a state of polypragmasia. Analysis of individual groups of drugs was able to reliably confirm the relationship between the appointment of drugs that increase.

PMID: 32145170 [PubMed - indexed for MEDLINE]

18 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 2020/04/16

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.

17 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 2020/04/16

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.

Signal of potentially protective drug-drug interactions from spontaneous reporting systems: proceed with caution.

Acta Diabetol. 2020 01;57(1):115-116

Authors: Antonazzo IC, Poluzzi E, Forcesi E, Salvo F, Pariente A, Marchesini G, De Ponti F, Raschi E

PMID: 31691870 [PubMed - indexed for MEDLINE]

Use of Genetic Variants Related to Antihypertensive Drugs to Inform on Efficacy and Side Effects.

Circulation. 2019 07 23;140(4):270-279

Authors: Gill D, Georgakis MK, Koskeridis F, Jiang L, Feng Q, Wei WQ, Theodoratou E, Elliott P, Denny JC, Malik R, Evangelou E, Dehghan A, Dichgans M, Tzoulaki I

Abstract
BACKGROUND: Drug effects can be investigated through natural variation in the genes for their protein targets. The present study aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are among the most commonly used medications worldwide.
METHODS: Genetic proxies for the effect of antihypertensive drug classes were identified as variants in the genes for the corresponding targets that associated with systolic blood pressure at genome-wide significance. Mendelian randomization estimates for drug effects on coronary heart disease and stroke risk were compared with randomized, controlled trial results. A phenome-wide association study in the UK Biobank was performed to identify potential side effects and repurposing opportunities, with findings investigated in the Vanderbilt University biobank (BioVU) and in observational analysis of the UK Biobank.
RESULTS: Suitable genetic proxies for angiotensin-converting enzyme inhibitors, β-blockers, and calcium channel blockers (CCBs) were identified. Mendelian randomization estimates for their effect on coronary heart disease and stroke risk, respectively, were comparable to results from randomized, controlled trials against placebo. A phenome-wide association study in the UK Biobank identified an association of the CCB standardized genetic risk score with increased risk of diverticulosis (odds ratio, 1.02 per standard deviation increase; 95% CI, 1.01-1.04), with a consistent estimate found in BioVU (odds ratio, 1.01; 95% CI, 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to nondihydropyridine CCBs (hazard ratio 1.49 considering thiazide diuretic agents as a comparator; 95% CI, 1.04-2.14) but not dihydropyridine CCBs (hazard ratio, 1.04; 95% CI, 0.83-1.32).
CONCLUSIONS: Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications. The identified potential effect of nondihydropyridine CCBs on diverticulosis risk could have clinical implications and warrants further investigation.

PMID: 31234639 [PubMed - indexed for MEDLINE]

Checkpoint Inhibitors.

Dtsch Arztebl Int. 2019 02 22;116(8):119-126

Authors: Heinzerling L, de Toni EN, Schett G, Hundorfean G, Zimmer L

Abstract
BACKGROUND: Treatment with checkpoint inhibitors such as anti-programmed death-1 (anti-PD-1), anti-PD-ligand 1 (anti-PD-L1), and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) antibodies can prolong the survival of cancer patients, but it also induces autoimmune side effects in 86-96% of patients by activating the immune system. In 17-59% of patients, these are severe or even life-threatening.
METHODS: This review is based on pertinent articles retrieved by a search in PubMed and on an evaluation of a side-effect registry.
RESULTS: Checkpoint-inhibitor-induced autoimmune side effects manifest themselves in all organ systems, most commonly as skin lesions (46-62%), autoimmune colitis (22-48%), autoimmune hepatitis (7-33%), and endocrinopathies (thyroiditis, hypophysitis, adrenalitis, diabetes mellitus; 12-34%). Rarer side effects include pneumonitis (3-8%), nephritis (1-7%), cardiac side effects including cardiomyositis (5%), and neurological side effects (1-5%). Severe (sometimes lethal) side effects arise in 17-21%, 20-28%, and 59% of patients undergoing anti-PD-1 and anti- CTLA-4 antibody treatment and the approved combination therapy, respectively. With proper monitoring, however, these side effects can be recognized early and, usually, treated with success. Endocrine side effects generally require long-term hormone substitution. Patients who have stopped taking checkpoint inhibitors because of side effects do not show a poorer response of their melanoma or shorter survival in comparison to patients who continue to take checkpoint inhibitors.
CONCLUSION: The complex management of checkpoint-inhibitor-induced side effects should be coordinated in experienced centers. The creation of an interdisciplinary "tox team" with designated experts for organ-specific side effects has proven useful. Prospective registry studies based on structured documentation of side effects in routine clinical practice are currently lacking and urgently needed.

PMID: 30940340 [PubMed - indexed for MEDLINE]

19 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 2020/04/14

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.

A Systematic Review and Network Meta-analysis of Novel Androgen Receptor Inhibitors in Non-metastatic Castration-resistant Prostate Cancer.

Clin Genitourin Cancer. 2020 Mar 06;:

Authors: Hird AE, Magee DE, Bhindi B, Ye XY, Chandrasekar T, Goldberg H, Klotz L, Fleshner N, Satkunasivam R, Klaassen Z, Wallis CJD

Abstract
BACKGROUND: Among men with high-risk non-metastatic castrate-resistant prostate cancer (nmCRPC), we used network meta-analysis to compare non-steroidal anti-androgens (NSAAs) and stratified class-level meta-analysis to identify subgroups with particular benefit from NSAAs with androgen deprivation therapy versus androgen deprivation therapy alone.
MATERIALS AND METHODS: We performed a systematic review of phase III parallel-group randomized controlled trials in adult men with nmCRPC. Primary outcome was metastasis-free survival (MFS). Secondary outcomes included overall survival (OS), prostate-specific antigen (PSA) progression-free survival (PFS), and rates of grade 3 to 4 adverse events (AEs). We assessed class-level effects using random effects models; effect modification owing to subgroup effects using random-effects models to pool study-level differences; and comparative outcomes between agents using fixed-effect network models in a Bayesian framework.
RESULTS: Three randomized controlled trials were identified. Pooled MFS, PSA-PFS, and OS were significantly greater with NSAA versus placebo (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.25-0.41; HR, 0.08; 95% CI, 0.05-0.13; and HR, 0.74; 95% CI, 0.61-0.90, respectively). Subgroup analysis demonstrated a greater benefit with NSAAs in men with Eastern Cooperative Oncology Group performance status 0 (HR, 0.30; 95% CI, 0.24-0.38) versus 1 (HR, 0.45; 95% CI, 0.36-0.56; P = .005), but no difference owing to PSA doubling time (P = .43) or use of osteoclast targeting therapy (P = .77). Bayesian analysis showed apalutamide and enzalutamide had a 56% and 44% likelihood of maximizing MFS, respectively, with subgroup analysis demonstrating these agents were preferred regardless of PSA doubling time and performance status. There was a 44%, 41%, and 15% likelihood that apalutamide, darolutamide and enzalutamide offered the greatest OS benefit, respectively. Grade 3 to 4 AEs were more common with NSAAs (odds ratio [OR], 1.47; 95% CI, 1.27-1.71) and there was a 61% chance that darolutamide was preferred.
CONCLUSIONS: NSAAs improve survival in high-risk nmCRPC. Apalutamide and enzalutamide may result in improved oncologic outcomes. Darolutamide may result in fewer AEs. Phase IV data are needed to validate these findings.

PMID: 32278840 [PubMed - as supplied by publisher]

Pharmacist interventions for persons with intellectual disabilities: A scoping review.

Res Social Adm Pharm. 2020 Apr 01;:

Authors: Lee C, Ivo J, Carter C, Faisal S, Shao YW, Patel T

Abstract
INTRODUCTION: Persons with intellectual disabilities (ID) often have complex health needs due to the development of multiple comorbidities. Given the higher associated use of problematic medications, such as antipsychotics, and polypharmacy, persons with ID may be particularly vulnerable to adverse side effects. With their medication expertise, pharmacists have the potential to address medication related challenges experienced by this population.
OBJECTIVE: Explore what is known about the care pharmacists provide to persons with ID.
DESIGN: Following Arksey and O'Malley's 5-stage framework for scoping reviews, searches of the PubMed (MEDLINE), Ovid EMBASE, Ovid International Pharmaceutical Abstracts, Scopus and APA PsycINFO databases were conducted in January 2019 with no limits on publication date. Studies of participants diagnosed with ID or healthcare providers/caregivers of persons with ID that referenced a pharmacist care intervention were included. Studies with non-human populations and editorials, commentaries, letters to the editor or discussion papers were excluded.
RESULTS: Twenty-six studies were included in the review. Seventy-six pharmacist care interventions were identified in cognitive pharmacy services (n = 46); educational and advisory services (n = 20); and medication prescription processing (n = 10). Fifty-one outcomes were referenced including drug-related interventions (n = 14), drug related problems (n = 9), cost/time-effectiveness (n = 7), secondary symptoms (n = 6), other outcomes (n = 5), general medication usage (n = 4), caregiver and healthcare team satisfaction levels (n = 3), and educational/knowledge (n = 3).
CONCLUSION: Pharmacists perform a variety of health care services to persons with ID but the impact of these interventions cannot be accurately measured due to a lack of: 1) universal definitions for ID; 2) reporting of multifactorial conditions contributing to a spectrum of ID severity; and 3) standardized reporting of ID-specific outcomes. Addressing these gaps is necessary for the development of a comprehensive evidence base regarding pharmacist involvement for medication challenges in persons with ID.

PMID: 32276871 [PubMed - as supplied by publisher]

Evocalcet in patients with primary hyperparathyroidism: an open-label, single-arm, multicenter, 52-week, dose-titration phase III study.

J Bone Miner Metab. 2020 Apr 09;:

Authors: Takeuchi Y, Nishida Y, Kondo Y, Imanishi Y, Fukumoto S

Abstract
INTRODUCTION: Primary hyperparathyroidism (PHPT) is caused by parathyroid adenoma, primary parathyroid hyperplasia, or parathyroid carcinoma. For some patients with PHPT controlling serum calcium levels is critical.
MATERIALS AND METHODS: We conducted an open-label, single-arm, 52-week, phase III study in Japanese patients with hypercalcemia due to PHPT to demonstrate efficacy and safety of evocalcet, a new calcimimetic. Patients with intractable PHPT (n = 13), postsurgical recurrence (n = 2), and parathyroid carcinoma (n = 3) were enrolled. Evocalcet administration started at a dose of 2 mg once or twice daily and was titrated to achieve the target serum corrected calcium (cCa) concentration (≤ 10.3 mg/dL) for two consecutive weeks (maximal dose 24 mg/day).
RESULTS: Fourteen patients achieved the target (77.8%; 95% confidence interval [CI] 52.4-93.6). The lower limit of 95% CI exceeded the predetermined reference limit (11%), and thus, efficacy was confirmed. Of 18 patients, 12 (66.7%; 95% CI 41.0-86.7) showed decreased serum cCa of ≥ 1.0 mg/dL from the baseline for two consecutive weeks during the titration phase. Sixteen patients entered the maintenance phase, and 15 patients completed the study. Treatment-emergent adverse events (TEAEs) were recorded in 18/18 patients (100%) and drug-related TEAEs in 8/18 (44.4%). The most commonly observed drug-related TEAE was nausea (2/18 patients). No unexpected drug-related TEAEs were observed. All drug-related TEAEs were mild in severity. No patient discontinued the study because of drug-related TEAEs.
CONCLUSION: Evocalcet demonstrated long-term effectiveness in reducing serum cCa concentrations and safety without any unexpected drug-related TEAEs in PHPT patients.

PMID: 32274572 [PubMed - as supplied by publisher]

Initial Experience of Ramucirumab Treatment After Lenvatinib Failure for Patients With Advanced Hepatocellular Carcinoma.

Anticancer Res. 2020 Apr;40(4):2089-2093

Authors: Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T, Fujishiro M

Abstract
BACKGROUND/AIM: The outcomes of ramucirumab after lenvatinib failure for hepatocellular carcinoma (HCC) patients with alpha fetoprotein (AFP) levels of ≥400 ng/ml are unknown.
PATIENTS AND METHODS: Of 12 patients treated with ramucirumab after lenvatinib failure, 10 patients were enrolled in this retrospective study.
RESULTS: The disease control rate of 80% at 6 weeks and the median time to progression of 3.1 months were the same by both the Response Evaluation Criteria in Solid Tumors (RECIST) and the modified RECIST. AFP reduction was seen in 5 patients at 2 weeks and in 3 patients at 6 weeks. The incidence of grade 3 adverse events was low at 10%. The albumin-bilirubin scores within 6 weeks did not worsen.
CONCLUSION: Ramucirumab might have potential therapeutic efficacy and safety in advanced HCC patients after lenvatinib failure. Further studies are needed to confirm the outcomes of ramucirumab after lenvatinib failure.

PMID: 32234901 [PubMed - indexed for MEDLINE]

[Systemic drug treatment during pregnancy].

Hautarzt. 2020 Apr;71(4):313-323

Authors: Riedel M, Kuschel B

Abstract
In clinical routine, treatment of pregnant women is a recurring challenge. The frequent opacity of current studies, lack of reliable sources of information and the general insecurity of pregnant women towards systemic drug treatment leads to difficult clinical decision making. Potent therapies with sufficient clinical experience in terms of safety of application are available for most diseases seen in pregnancy. After careful evaluation of potential benefits and risks of a therapy, not only the optimal choice of a medical treatment, but also adequate control of clinical symptoms and interdisciplinary care are crucial for a safe pregnancy.

PMID: 32162050 [PubMed - indexed for MEDLINE]

Effectiveness of pharmacist home visits for individuals at risk of medication-related problems: a systematic review and meta-analysis of randomised controlled trials.

BMC Health Serv Res. 2020 Jan 15;20(1):39

Authors: Abbott RA, Moore DA, Rogers M, Bethel A, Stein K, Coon JT

Abstract
BACKGROUND: Medication mismanagement is a major cause of both hospital admission and nursing home placement of frail older adults. Medication reviews by community pharmacists aim to maximise therapeutic benefit but also minimise harm. Pharmacist-led medication reviews have been the focus of several systematic reviews, but none have focussed on the home setting.
REVIEW METHODS: To determine the effectiveness of pharmacist home visits for individuals at risk of medication-related problems we undertook a systematic review and meta-analysis of randomised controlled trials (RCTs). Thirteen databases were searched from inception to December 2018. Forward and backward citation of included studies was also performed. Articles were screened for inclusion independently by two reviewers. Randomised controlled studies of home visits by pharmacists for individuals at risk of medication-related problems were eligible for inclusion. Data extraction and quality appraisal were performed by one reviewer and checked by a second. Random-effects meta-analyses were performed where sufficient data allowed and narrative synthesis summarised all remaining data.
RESULTS: Twelve RCTs (reported in 15 articles), involving 3410 participants, were included in the review. The frequency, content and purpose of the home visit varied considerably. The data from eight trials were suitable for meta-analysis of the effects on hospital admissions and mortality, and from three trials for the effects on quality of life. Overall there was no evidence of reduction in hospital admissions (risk ratio (RR) of 1.01 (95%CI 0.86 to 1.20, I2 = 69.0%, p = 0.89; 8 studies, 2314 participants)), or mortality (RR of 1.01 (95%CI 0.81 to 1.26, I2 = 0%, p = 0.94; 8 studies, 2314 participants)). There was no consistent evidence of an effect on quality of life, medication adherence or knowledge.
CONCLUSION: A systematic review of twelve RCTs assessing the impact of pharmacist home visits for individuals at risk of medication related problems found no evidence of effect on hospital admission or mortality rates, and limited evidence of effect on quality of life. Future studies should focus on using more robust methods to assess relevant outcomes.

PMID: 31941489 [PubMed - indexed for MEDLINE]

Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil.

J Bras Pneumol. 2019 Sep 16;45(5):e20180414

Authors: Pereira CAC, Baddini-Martinez JA, Baldi BG, Jezler SFO, Rubin AS, Alves RLR, Zonzin GA, Quaresma M, Trampisch M, Rabahi MF

Abstract
OBJECTIVE: Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population.
METHODS: Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events.
RESULTS: The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event.
CONCLUSION: In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

PMID: 31531619 [PubMed - indexed for MEDLINE]

Handling of symptomatic adverse events in breast cancer patients receiving adjuvant chemotherapy in a cluster randomized trial with electronic patient-reported outcomes as intervention.

Breast J. 2019 11;25(6):1295-1296

Authors: Baeksted CW, Nissen A, Knoop A, Christiansen M, Pappot H

PMID: 31353754 [PubMed - indexed for MEDLINE]