Differential Diagnoses and Clinical Implications of Medication Nonadherence in Older Patients with Chronic Kidney Disease: A Review.

Drugs Aging. 2020 Oct 08;:

Authors: Owsiany MT, Hawley CE, Paik JM

Abstract
Older adults with chronic kidney disease (CKD) often have many comorbidities, which requires them to take multiple medications. As the number of daily medications prescribed increases, the risk for polypharmacy increases. Understanding and improving medication adherence in this patient population is vital to avoiding the drug-related adverse events of polypharmacy. The primary objective of this review is to summarize the existing literature and to understand the factors leading to medication nonadherence in older patients with CKD. In this review, we discuss the prevalence of polypharmacy, the current lack of consensus on the incidence of medication nonadherence, the heterogeneity of assessing medication adherence, and the most common differential diagnoses for medication nonadherence in this population. Specifically, the most common differential diagnoses for medication nonadherence in older adults with CKD are (1) medication complexity; (2) cognitive impairment; (3) low health literacy; and (4) systems-based barriers. We provide tailored strategies to address these differential diagnoses and subsequently improve medication adherence. The clinical implications include deprescribing to decrease medication complexity and polypharmacy, utilizing a team-based approach to identify and support patients with cognitive impairment, enriching communication between health providers and patients with low health literacy, and improving health care access to address systems-based barriers. Further research is needed to determine the effects of addressing these differential diagnoses and medication adherence in older adults with CKD.

PMID: 33030671 [PubMed - as supplied by publisher]

Pemetrexed-induced Sweet Syndrome: First case report in the medical literature.

J Oncol Pharm Pract. 2020 Oct 07;:1078155220963178

Authors: Korkmaz M, Eryılmaz MK, Karaağaç M, Demirkıran A, Araz M, Artaç M

Abstract
INTRODUCTION: Sweet Syndrome, also known as acute febrile neutrophilic dermatosis, is a rare inflammatory disease characterized by the sudden emergence of painful, edematous, and erythematous papules, plaques, or nodules on the skin, which usually fully responsive to systemic corticosteroids. Skin lesions are often accompanied by fever and leukocytosis. Here we present a case of Sweet Syndrome caused by pemetrexed in metastatic lung adenocarcinoma.
CASE REPORT: A 52-year-old patient with metastatic lung adenocarcinoma received multiple lines of chemotherapy. The patient presented with extensive skin lesions after performing of pemetrexed chemotherapy. He had a fever and elevations in blood levels of C-reactive protein (CRP), sedimentation, leucocytes, and neutrophils. Neutrophil predominant perivascular and interstitial dermatitis, focal micropustule formation, and severe neutrophilic dermatosis were reported in skin biopsy. Topical steroid and oral antihistamine treatment were started as initial treatment.Discussion and conclusions: Cutaneous side effects related to pemetrexed are often reported as 'skin rash,' which is a non-specific term. Therefore, the diagnosis of Sweet Syndrome must be confirmed by skin biopsy. It is essential to exclude the presence of an infection and medication history. Recovery in drug-induced Sweet Syndrome occurs after the drug that caused it was discontinued. Systemic corticosteroids are the first-line treatment for most cases.

PMID: 33028131 [PubMed - as supplied by publisher]

Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events.

Eur J Cancer. 2020 03;128:17-26

Authors: Cortellini A, Bersanelli M, Santini D, Buti S, Tiseo M, Cannita K, Perrone F, Giusti R, De Tursi M, Zoratto F, Marconcini R, Russano M, Zeppola T, Anesi C, Filetti M, Marchetti P, Botticelli A, Gelibter A, De Galitiis F, Vitale MG, Rastelli F, Tudini M, Silva RR, Atzori F, Chiari R, Ricciuti B, De Giglio A, Migliorino MR, Mallardo D, Vanella V, Mosillo C, Bracarda S, Rinaldi S, Berardi R, Natoli C, Ficorella C, Porzio G, Ascierto PA

Abstract
BACKGROUND: Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients.
PATIENTS AND METHODS: We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI.
RESULTS: One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21-92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6-46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p < 0.0001), G3/G4 irAEs (p < 0.0001) and irAEs leading to discontinuation (LTD) (p < 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5-14.9 for overweight, and 16.6 (95%CI: 10.3-26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4-22.3], p < 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3-18.2], p < 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients.
CONCLUSIONS: Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'.

PMID: 32109847 [PubMed - indexed for MEDLINE]

Recurrent Immediate Type Hypersensitivity Reaction Induced by Macrogol in a 3-Year-Old Boy.

J Investig Allergol Clin Immunol. 2020 Feb;30(1):72-73

Authors: Hamano S, Nishima D, Satake M, Kudo K, Yanagita K, Tezuka J

PMID: 32077856 [PubMed - indexed for MEDLINE]

Time series analysis of delta neutrophil index as the predictor of sepsis in patients with acute poisoning.

Hum Exp Toxicol. 2020 Jan;39(1):86-94

Authors: Park SJ, Park J, Lee MJ, Seo JS, Ahn JY, Cho JW

Abstract
Delta neutrophil index (DNI), which reflects the fraction of immature granulocytes, is used to detect infection and sepsis from noninfectious conditions, but few studies have evaluated in the early stage of acute poisoning. This retrospective observational study was performed on acute poisoning patients who visited to the emergency department (ED) and were consecutively admitted in intensive care units over 18-month period. The serial DNI, conventional inflammatory biomarkers, and culture results were obtained in the ED and after admission. The outcomes were the identification of sepsis, bacteremia, and 30-day mortality. Of 166 patients (mean age, 56.0 years) in this cohort, 59 (35.5%) had sepsis and 29 (17.5%) had bacteremia. Initial and peak DNI fractions 24 h after ED admission were strong independent predictors of sepsis development. Analysis of the area under the curve according to multiple receiver operating characteristics showed that DNI had a higher capability to predict sepsis than other parameters (0.815 for DNI, 0.700 for procalcitonin, 0.681 for C-reactive protein, and 0.741 for white blood cell). Using multivariable logistic regression analysis, it was found that DNI was an independent predictor of sepsis (95% confidence interval (CI) of odds: 1.03-1.18) and bacteremia (95% CI: 1.01-1.14). Therefore, initial and serial measurement of DNI may serve as useful risk predictor for development of sepsis or bacteremia in acute poisoning.

PMID: 31558056 [PubMed - indexed for MEDLINE]

Multiple Drug Hypersensitivity Syndrome to Antituberculosis Drugs: A Case Report.

J Investig Allergol Clin Immunol. 2020;30(1):70-71

Authors: Carneiro-Leão L, Gomes I, Freitas C, Costa E Silva M, Viseu R, Cernadas J

PMID: 31530510 [PubMed - indexed for MEDLINE]

Real-world Performance of Meta-analysis Methods for Double-Zero-Event Studies with Dichotomous Outcomes Using the Cochrane Database of Systematic Reviews.

J Gen Intern Med. 2019 06;34(6):960-968

Authors: Ren Y, Lin L, Lian Q, Zou H, Chu H

Abstract
BACKGROUND: Meta-analysis combines multiple independent studies, which can increase power and provide better estimates. However, it is unclear how best to deal with studies with zero events; such studies are also known as double-zero-event studies (DZS). Several statistical methods have been proposed, but the agreement among different approaches has not been systematically assessed using real-world published systematic reviews.
METHODS: The agreement of five commonly used methods (i.e., the inverse-variance, Mantel-Haenszel, Peto, Bayesian, and exact methods) was assessed using the Cohen's κ coefficients using 368 meta-analyses with rare events selected from the Cochrane Database of Systematic Reviews. Three continuity corrections, including the correction of a constant 0.5, the treatment arm continuity correction (TACC), and the empirical (EMP) correction, were used to handle DZS when applying inverse-variance and Mantel-Haenszel methods.
RESULTS: When the proportion of DZS studies was lower than 50% in a meta-analysis, different methods had moderately high agreement. However, when this proportion was increased to be over 50%, the agreement among the methods decreased to different extents. For the Bayesian, exact, and Peto methods and the inverse-variance and Mantel-Haenszel methods using the EMP correction, their agreement coefficients with the inverse-variance and Mantel-Haenszel methods using a constant 0.5 and TACC decreased from larger than 0.70 to smaller than 0.30. In contrast, the agreement coefficients only decreased slightly among the Bayesian, exact, and Peto methods and the inverse-variance and Mantel-Haenszel methods using the EMP correction.
CONCLUSIONS: To utilize all available information and reduce research waste and avoid overestimating the effect, meta-analysts should incorporate DZS, rather than simply removing them. The Peto and other conventional methods with continuity correction should be avoided when the proportion of DZS is extremely high. The exact and Bayesian methods are highly recommended, except when none of the included studies have an event in one or both treatment arms.

PMID: 30887438 [PubMed - indexed for MEDLINE]

Review of Published Bitter Orange Extract and p-Synephrine Adverse Event Clinical Study Case Reports.

J Diet Suppl. 2020;17(3):355-363

Authors: Stohs SJ, Ray SD

Abstract
p-Synephrine is the primary active ingredient in bitter orange (Citrus aurantium) extract and is present in other citrus species. This review summarizes all known case reports that have been published regarding adverse events associated with multi-ingredient dietary supplements containing bitter orange extract. A common characteristic of all the case studies was the assumption that if bitter orange extract is listed on the label of the product it is the most likely cause of any adverse effect, although in no case was the presence of p-synephrine determined or a direct link demonstrated. No case study reviewed the existing published literature, and all failed to note that numerous clinical studies have not demonstrated adverse effects at commonly used doses. Most studies did not indicate the composition of the product involved, and no study analyzed the product in question. In no case was a direct correlation between the event and p-synephrine made. Although p-synephrine and ephedrine have some structural similarity, the structural differences result in markedly different pharmacokinetic, physiological, and pharmacological effects, and thus the effects produced by ephedrine cannot be extrapolated to p-synephrine.

PMID: 30835576 [PubMed - indexed for MEDLINE]

Nonasthmatic eosinophilic bronchitis in an ulcerative colitis patient - a putative adverse reaction to mesalazine: A case report and review of literature.

World J Clin Cases. 2020 Sep 26;8(18):4162-4168

Authors: Cernomaz AT, Bordeianu G, Terinte C, Gavrilescu CM

Abstract
BACKGROUND: Lung and airway involvement in inflammatory bowel disease are increasingly frequently reported either as an extraintestinal manifestation or as an adverse effect of therapy.
CASE SUMMARY: We report a case of a patient with ulcerative colitis controlled under mesalazine treatment who presented with chronic cough and hemoptysis. Chest computed tomography and bronchoscopy findings supported tracheal involvement in ulcerative colitis; pathology examination demonstrated an unusual eosinophil-rich inflammatory pattern, and together with clinical data, a nonasthmatic eosinophilic bronchitis diagnosis was formulated. Full recovery was observed within days of mesalazine discontinuation.
CONCLUSION: Mesalazine-induced eosinophilic respiratory disorders have been previously reported, generally involving the lung parenchyma. To the best of our knowledge, this is the first report of mesalamine-induced eosinophilic involvement in the upper airway.

PMID: 33024774 [PubMed]

Management of pembrolizumab-induced steroid refractory mucositis with infliximab: A case report.

World J Clin Cases. 2020 Sep 26;8(18):4100-4108

Authors: Dang H, Sun J, Wang G, Renner G, Layfield L, Hilli J

Abstract
BACKGROUND: Pembrolizumab is an anti-programmed death receptor 1 (PD-1) that was shown to have a tolerable safety profile with 17% of grade 3-4 drug-related adverse events, notable response rate of 16% with median duration of response of 8 mo, and median overall survival of 8 mo. Severe mucositis is a very rare complication with only two cases of grade 4 mucositis reported, and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone tapering. We report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment.
CASE SUMMARY: An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 mo. She initially received 2 doses of ipilimumab 1 year ago with good outcome, but treatment was discontinued after developing severe diarrhea and rash. Pembrolizumab was then initiated 4 mo after disease progression. Significant improvement was noted after 3 doses. However, after 6 cycles of pembrolizumab, patient developed odynophagia and malnutrition. Improvement of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids. 3 mo later, patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen, finally ended up with intubation and tracheostomy. Histologic analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation, negative for malignancy and infection. Patient achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering course.
CONCLUSION: We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of infliximab. The patient had recurrent mucositis symptoms whenever steroids was tapered but achieved complete response after receiving two doses of infliximab while continuing to be on tapering steroids. The success of infliximab in this patient with pembrolizumab-induced severe mucositis presents a potentially safe approach to reduce prolonged steroid course and accelerate recovery in managing this rare complication.

PMID: 33024767 [PubMed]

Interprofessional medication assessment among home care patients: any impact on functioning? Results from a randomised controlled trial.

BMC Geriatr. 2020 Oct 06;20(1):390

Authors: Auvinen K, Voutilainen A, Jyrkkä J, Lönnroos E, Mäntyselkä P

Abstract
BACKGROUND: Multimorbidity and polypharmacy are related to the use of potentially inappropriate medicines and negative clinical outcomes including drug-related adverse events and functional declines. Home care clients are a vulnerable patient group often exposed to these risks. The aim of this study was to examine whether an interprofessional medication assessment can influence the functioning of home care patients.
METHODS: The FIMA study was a randomised controlled intervention study comparing a general practitioner-led interprofessional medication assessment conducted at the baseline of the study with usual care with a six-month follow-up. We used linear mixed models (LMM) with a random subject effect to detect differences between the usual care and intervention groups in the following outcome measures; Katz index of Activities of Daily Living (ADL), Lawton and Brody scale of Instrumental Activities of Daily Living, Timed up and go-test (TUG), Mini-Mental State Examination, Geriatric Depression Scale and the 3-level version of EQ-5D.
RESULTS: Home care patients (n = 512) had major disease burdens and functional limitations. Regarding TUG times, the LMM detected a one second improvement in the FIMA group and 2.4 s worsening in the usual care group. However, the result was not statistically significant. The ADL revealed an interaction across time, treatment and sex (p = 0.026). The ADL score decreased in both groups; the decline being the steepest among women in the intervention group.
CONCLUSIONS: In general, medication assessments may have limited impact on functioning of older people. Nonetheless, the FIMA intervention may prevent worsening of mobility among older home care patients.
TRIAL REGISTRATION: The Interprofessional Medication Assessment for Older Patients, Clinical Trials.gov. NCT02398812 . First registration, 26 March 2015. Retrospectively registered.

PMID: 33023497 [PubMed - in process]

Early experience with remdesivir in SARS-CoV-2 pneumonia.

Infection. 2020 Oct;48(5):779-782

Authors: Durante-Mangoni E, Andini R, Bertolino L, Mele F, Florio LL, Murino P, Corcione A, Zampino R

Abstract
At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.

PMID: 32418190 [PubMed - indexed for MEDLINE]

Relative efficacy and safety of inhaled corticosteroids in patients with asthma: Systematic review and network meta-analysis.

Ann Allergy Asthma Immunol. 2020 08;125(2):163-170.e3

Authors: Chipps B, Taylor B, Bayer V, Shaikh A, Mosnaim G, Trevor J, Rogers S, Del Aguila M, Paek D, Wechsler ME

Abstract
BACKGROUND: Inhaled corticosteroids (ICSs) are recommended as first-line controller medications for persistent asthma. However, guidelines on the initial ICS doses, step-up and step-down algorithms, and when to switch to combination therapy vary.
OBJECTIVE: To understand the ideal starting doses of ICS therapy based on current evidence and to systematically compare low, moderate, and high starting doses of ICSs as monotherapy and in combination with long-acting β-agonists with respect to efficacy and safety.
METHODS: MEDLINE, Embase, and Cochrane databases were searched for relevant English-language articles published from 1980 to November 17, 2018. Randomized controlled trials with adult, steroid-naive, ICS-free (for ≥4 weeks) patients with asthma and a duration of 4 weeks or longer with an ICS treatment arm (monotherapy or combination therapy) were included. Separate fixed-effects Bayesian network meta-analyses were conducted on the extracted data for peak expiratory flow, forced expiratory volume in 1 second, nighttime rescue medication use, nighttime symptom score, and study withdrawal because of an adverse event.
RESULTS: A total of 31 randomized controlled trials were analyzed. All starting doses of ICSs were comparable with respect to nighttime rescue medication use, nighttime symptom score, change in forced expiratory volume in 1 second, and study withdrawal because of an adverse event. Significant improvement in morning peak expiratory flow was observed with high-dose ICSs and with low- and moderate-dose ICSs and long-acting β-agonists than with low-dose ICSs.
CONCLUSION: Overall, a high starting dose of ICSs had no additional clinical benefit in 3 of the 4 efficacy parameters compared with low or moderate ICS doses for controlling moderate to severe asthma but might have potential safety concerns.

PMID: 32302768 [PubMed - indexed for MEDLINE]

Author reply.

Intern Med J. 2020 04;50(4):507-508

Authors: Sivashanmugarajah A, Fulcher J, Sullivan D, Elam M, Jenkins A, Keech A

PMID: 32270619 [PubMed - indexed for MEDLINE]

Pharmacogenetics of statin intolerance.

Intern Med J. 2020 04;50(4):506-507

Authors: Suthers G, Somogyi AA

PMID: 32270606 [PubMed - indexed for MEDLINE]

Spontaneous adverse drug reaction reports on patients with cirrhosis: analysis of the nature, quantity and quality of the reports.

Eur J Clin Pharmacol. 2020 May;76(5):741-743

Authors: Weersink RA, Taxis K, van Puijenbroek EP, Borgsteede SD

PMID: 32052091 [PubMed - indexed for MEDLINE]

Factors associated with spontaneous adverse drug reaction reporting among healthcare professionals in Vietnam.

J Clin Pharm Ther. 2020 Feb;45(1):122-127

Authors: Le TT, Nguyen TTH, Nguyen C, Tran NH, Tran LA, Nguyen TB, Nguyen N, Nguyen HA

Abstract
WHAT IS KNOWN AND OBJECTIVE: Under-reporting is a major drawback of a voluntary adverse drug reaction reporting system in pharmacovigilance. However, little is known about facilitators and barriers to ADR reporting by healthcare professionals (HCPs) in developing countries. To investigate factors associated with adverse drug reaction (ADR) reporting among HCPs in Vietnam.
METHODS: A cross-sectional survey of 2091 HCPs was conducted in 2015 at 10 hospitals throughout Vietnam. The binary outcome was ever reporting ADRs. Healthcare professionals knowledge, attitude and practice about ADR reporting were measured. Multiple logistic regression analyses examined factors significantly associated with ever ADR reporting.
RESULTS: Overall, 29.3%, 2.2% and 68.4% of the sample were doctors, pharmacists and nurses, respectively. More than half (59.3%) had ever reported any ADR. Facilitators for ADR reporting were educational training (OR = 1.77, 95%CI = 1.42-2.22) and having better knowledge, such as awareness of ADR reporting regulation (OR = 1.63, 95%CI = 1.19-2.21), of reporting time (OR = 1.76, 95%CI = 1.35-2.29) and of necessary information in reporting form (OR = 1.94, 95%CI = 1.53-2.45).Conversely, barriers to non-reporting were unknown of reporting procedure (OR = 0.27, 95%CI = 0.22-0.35), unavailability of reporting form (OR = 0.54, 95%CI = 0.42-0.68) and lack of time (OR = 0.59, 95%CI = 0.46-0.74).
WHAT IS NEW AND CONCLUSION: Given the low ADR reporting rate among HCPs, educational interventions to improve their knowledge and attitude should be prioritized in Vietnam. Additional interventions addressing obstacles (i.e. availability and complexity of reporting form, lack of time) should be considered to improve both the quantity and quality of ADR reporting.

PMID: 31486525 [PubMed - indexed for MEDLINE]

Symptoms of Toxicity and Plasma Cytochrome c Levels in Human Immunodeficiency Virus-infected Patients Receiving Anti-retroviral Therapy in Ghana: A Cross-sectional Study.

Infect Disord Drug Targets. 2020;20(1):88-97

Authors: Mensah EA, Sarfo B, Bonney EY, Parbie PK, Ocloo A

Abstract
BACKGROUND: Side effects and toxicity have posed a threat to the positive contribution of Antiretroviral Therapy (ART) in the management of human immunodeficiency virus (HIV) infection and Acquired Immune Deficiency Syndrome (AIDS). Symptoms of mitochondrial toxicity including myopathy, pancreatitis, hyperlipidaemia and lactic acidosis are found among HIVinfected patients on ART. To date, there is not a reliable biomarker for monitoring ART-related mitochondrial toxicity. Plasma level of Cytochrome c (Cyt-c) has been proposed as a potential biomarker for ART-related toxicity due to its strong association with apoptosis.
OBJECTIVE: The present study assessed toxicity and level of plasma Cyt-c among HIV-infected patients receiving ART in Ghana.
METHODS: A total of eighty (80) HIV patients were recruited into the study. Demographic data were obtained from personal interview and medical records. Plasma samples were screened for toxicity from sixty (60) participants due to limited resources, and plasma Cyt-c levels were determined using ELISA. Data were analyzed using Stata version 13.
RESULTS: Out of the 60 participants, 11 (18.3%) were found with symptoms of myopathy, 12 (20%) with pancreatitis, 21 (35%) with hyperlipidaemia and 36 (60%) with at least one of the symptoms. The concentration of plasma Cyt-c was higher (0.122 ng/ml) in patients with toxicity than in those without toxicity (0.05 ng/ml), though the difference was not statistically significant (p = 0.148). There was a weak correlation between plasma Cyt-c level and duration of ART (Spearman rho = 0.02, p = 0.89).
CONCLUSION: This study, therefore, demonstrated a high prevalence of ART-related toxicity and high levels of Cyt-c in HIV-infected patients in support of the argument that plasma Cyt-c levels are potential biomarkers for determining ART-related toxicity in HIV patients.

PMID: 30387403 [PubMed - indexed for MEDLINE]

Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, And Management Guidelines.

Oncologist. 2020 Oct 05;:

Authors: Lacouture ME, Sibaud V, Anadkat MJ, Kaffenberger B, Leventhal J, Guindon K, Abou-Alfa G

Abstract
Fibroblast growth factor receptor (FGFR) tyrosine kinases, which are expressed on the cell membrane, are involved in a wide range of biological functions such as cell proliferation, survival, migration, and differentiation. The identification of FGFR fusions and other alterations in a wide range of solid tumors, including cholangiocarcinoma and bladder cancer, has resulted in the development of several selective FGFR inhibitors for use in these indications, for example infigratinib, erdafitinib, derazantinib, pemigatinib, and futibatinib. In addition to the typical adverse events associated with tyrosine kinases, the FGFR inhibitors appear to give rise to a number of adverse events affecting the skin. Here we describe these skin events, which include the more common nail adverse events (e.g., onycholysis), palmar-plantar erythrodysesthesia syndrome, and stomatitis, as well as less common reactions such as calciphylaxis. This review aims to provide oncologists with an understanding of these dermatologic events and proposes guidelines for the management of treatment-emergent dermatologic adverse events. Awareness of possible adverse events associated with specific drugs should allow physicians to educate patients as to what to expect and implement effective management plans at the earliest possible opportunity, thereby preventing premature discontinuation while maintaining patient quality of life. IMPLICATIONS FOR PRACTICE: Identification of FGFR aberrations in cancers such as cholangiocarcinoma and bladder cancer led to development of selective FGFR inhibitors for these indications, based on clinical benefit and safety profiles. The most frequent adverse events (AEs) include those affecting the skin, hair, and nails, a unique class effect of these agents. These are usually mild to moderate in severity. We reviewed skin AEs reported with FGFR inhibitors and provide management and supportive care guidelines for physicians, aiming to increase awareness of skin events in clinical practice and provide practical guidance on the most effective treatment strategies. Early intervention and effective management may improve treatment adherence, optimize outcomes, and improve patient quality of life.

PMID: 33021006 [PubMed - as supplied by publisher]

Successful treatment of a patient with small cell lung cancer receiving hemodialysis, with concurrent oral etoposide and radiotherapy: A case report.

Medicine (Baltimore). 2020 Oct 02;99(40):e22637

Authors: Gao F, Cong X, Liu Z

Abstract
INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignancy that progresses rapidly and easily relapses. To the best of our knowledge, advances have been minimal for decades and the first-line treatment is still platinum-etoposide and radiotherapy. However, elderly patients with severe renal failure who suffer from SCLC usually show more serious drug-related side effects. A large proportion of them cannot tolerate the standard treatment, and their prognosis is poorer compared with that of younger patients. Presently, oral etoposide capsules may be accepted as a replaceable option. We report the case of a male patient with SCLC on hemodialysis who was successfully treated with concurrent oral etoposide monotherapy and radiotherapy and achieved excellent outcomes.
PATIENT'S CONCERNS: A 63-year-old man with severe renal failure was diagnosed with SCLC.
PRIMARY DIAGNOSES: SCLC was diagnosed using transbronchial biopsy.
INTERVENTIONS: He received concomitant single-agent oral etoposide (6 cycles) and local radiotherapy. Etoposide 100 mg once daily combined with thoracic radiation treatment (2 Gy/f, total DT: 50 Gy/25 f), was subsequently followed by prophylactic cranial irradiation plus anlotinib.
OUTCOMES: The patient achieved complete response after 1 cycle and the subsequent treatment was effective without any kidney damage and other severe side effects.
CONCLUSION: Though etoposide capsule is an old drug, its use should be considered in SCLC patients with renal insufficiency undergoing hemodialysis. However, treatment guidelines and research data for such patients are still lacking and further studies are needed. Although recent research focuses mainly on new drugs, some old drugs like etoposide which can bring unexpected positive effects should not be neglected.

PMID: 33019486 [PubMed - in process]