Farm Hosp. 2022 May 9;46(3):133-145.

ABSTRACT

OBJECTIVE: To analyse the applications for drugs in special situations (compassionate use, off-label use and foreign drugs) for solid tumours, and to assess the level of evidence supporting these applications, as well as the effectiveness and safety of most frequent drugs.

METHOD: We performed a cross-sectional study of all applications for drugs in special situations during 2018 and 2019 in a representative third-level centre. We collected data about generic names of drugs, clinical indications, and level of evidence provided on the application form. Furthermore, tumour response was assessed according to the Response Evaluation Criteria in Solid Tumours version 1.1., Progression Free Survival and Overall Survival. Safety was evaluated with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.

RESULTS: 2,273 drugs in special situations were approved between January 2018 and December 2019. In 431 cases (19%), they were used to treat solid tumours. Out of 431, 291 (67.5%) applications were offlabel drugs, 76 (18%) foreign drugs, and 64 (15%) were compassionate use of drugs. Most of them were supported by phase 3 (47%) or phase 2 (33%) clinical trials. The majority of adverse effects were grade 1 and only in 6/67 cases the treatment was discontinued due to toxicity.

CONCLUSIONS: A significant number of drugs in special situations are prescribed to Oncology patients. The majority of applications of these drugs was supported by clinical trials. The real-life experience showed an effectiveness and tolerance profile similar to those described in randomised clinical trials.

PMID:36183206

Medicine (Baltimore). 2022 Sep 30;101(39):e30955. doi: 10.1097/MD.0000000000030955.

ABSTRACT

RATIONALE: Drug induced liver injury (DILI) is a common side effect causing treatment discontinuation during tuberculosis (TB) treatment, and pyrazinamide (PZA) usually leads to a delayed and prolonged abnormal liver function of the 4 standard anti-tuberculosis regimens. However, a prolonged hepatitis lasting more than 4 months is rarely reported.

PATIENT CONCERNS: A 78-year-old man presented with general weakness and poor appetite on his seventh week of anti-TB treatment for tuberculosis lymphadenitis.

DIAGNOSIS: Drug induced liver injury, PZA-related. NAT2 slow acetylator phenotype was accidentally found during workup of DILI.

INTERVENTION: A liver biopsy was performed and PZA-related DILI was suspected. All anti-TB medications were therefore discontinued.

OUTCOME: After withholding all anti-TB medications for 4 months, the elevations of aminotransferases and hyperbilirubinemia completely resolved. Anti-TB therapy was switched to ethambutol and levofloxacin for 15 months without adverse events. Long-term ultrasound follow-up was performed and cervical lymphadenopathy completely resolved.

CONCLUSION: Our patient presents with PZA related prolonged DILI resolved after drug discontinuation for 4 months. NAT2 slow acetylator phenotype may be related to this condition through unknown mechanisms.

PMID:36181061 | DOI:10.1097/MD.0000000000030955

CNS Drugs. 2022 Oct;36(10):1113-1119. doi: 10.1007/s40263-022-00954-w. Epub 2022 Sep 30.

ABSTRACT

BACKGROUND: Eslicarbazepine acetate (ESL), a novel sodium channel blocker, is approved for mono and adjunctive treatment of partial epileptic seizures with or without secondary generalization. Its efficacy in primary generalized seizures has not yet been evaluated.

OBJECTIVE: To evaluate the efficacy and safety of ESL in primary generalized tonic-clonic seizures (PGTCS) in an observational study.

METHODS: The data were collected from a prospective population-based register. Effectiveness was measured as relative reduction in standardized seizure frequency (SSF), responder rate (≥ 50% reduction in SSF), and seizure freedom rate at 6 and 12 months after initiation of ESL. Safety and tolerability were evaluated using patients' diaries.

RESULTS: Fifty-six adult patients with PGTCS were treated with ESL as adjunctive therapy. Of these, 30.4% (n = 17) had myoclonic seizures in addition to PGTCS. The retention rate after 12 months was 80.4% (n = 45). After initiating ESL therapy, reduction in SSF for PGTCS on ESL was 56.0% after 6 months and 56.9% after 12 months (p < 0.01), whereas myoclonic seizures did not show any significant improvement in frequency. The responder rate for PGTCS was 64.3% after 6 months and 66.1% after 12 months, and seizure freedom was achieved in 32.1% and 35.7%, respectively. Forty-three patients (73.2%) reported no side effects. Among the reported side effects of ESL therapy, headache (7.1%), dizziness (8.9%), tiredness (7.1%), nausea (5.4%), and hyponatremia (5.4%) were the most prevalent.

CONCLUSIONS: Our data suggest that ESL may provide additional benefits in the treatment of patients with PGTCS and motivate randomized controlled trials in this indication.

PMID:36178588 | DOI:10.1007/s40263-022-00954-w

Iran J Kidney Dis. 2022 Sep;16(5):311-314.

ABSTRACT

INTRODUCTION: Cilostazol is an antiplatelet agent, that has been recently used as an adjunctive therapy in the management of diabetic foot ulcers. Headache, diarrhea, palpitations, and edema are reported as common side effects.

CASE PRESENTATION: A 53-year-old woman was admitted to hospital, with decreased urine output and increased serum creatinine level. She had taken Cilostazol for the first time, for only one day, so the diagnosis of acute kidney injury, probably drug-induced acute interstitial nephritis, due to Cilostazol use, was made. Her kidney function did not improve despite Cilostazol discontinuation and therefore, empirical corticosteroid therapy was initiated. Her urine output increased and her serum creatinine level significantly decreased, on the third day of treatment. She was discharged with acceptable kidney function. Follow-up visits showed gradual normalization of serum creatinine in the next 62 days.

CONCLUSION: Based on our case, we may draw the conclusion that, Cilostazol may cause nephrotoxicity at any point after ingestion. DOI: 10.52547/ijkd.6980.

PMID:36178866

Med Oncol. 2022 Sep 29;39(12):219. doi: 10.1007/s12032-022-01805-w.

ABSTRACT

The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 4362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary edema, pleural effusion, lung disorder, acute pulmonary edema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105 days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease.

PMID:36175697 | DOI:10.1007/s12032-022-01805-w

J Gen Intern Med. 2022 Sep 29. doi: 10.1007/s11606-022-07828-3. Online ahead of print.

ABSTRACT

BACKGROUND: While many older adults with type 2 diabetes have tight glycemic control beyond guideline-recommended targets, deintensifying (stopping or dose-reducing) diabetes medications rarely occurs.

OBJECTIVE: To explore the perspectives of older adults with type 2 diabetes around deintensifying diabetes medications.

DESIGN: This qualitative study used individual semi-structured interviews, which included three clinical scenarios where deintensification may be indicated.

PARTICIPANTS: Twenty-four adults aged ≥65 years with medication-treated type 2 diabetes and hemoglobin A1c <7.5% were included (to thematic saturation) using a maximal variation sampling strategy for diabetes treatment and physician specialty.

APPROACH: Interviews were independently coded by two investigators and analyzed using a grounded theory approach. We identified major themes and subthemes and coded responses to the clinical scenarios as positive (in favor of deintensification), negative, or ambiguous.

KEY RESULTS: Participants' mean age was 74 years, half were women, and 58% used a sulfonylurea or insulin. The first of four major themes was fear of losing control of diabetes, which participants weighed against the benefits of taking less medication (Theme 2). Few participants viewed glycemic control below target as a reason for deintensification and a majority would restart the medication if their home glucose increased. Some participants were anchored to their current diabetes treatment (Theme 3) driven by unrealistic views of medication benefits. A trusting patient-provider relationship (Theme 4) was a positive influence. In clinical scenarios, 8%, 4%, and 75% of participants viewed deintensification positively in the setting of poor health, limited life expectancy, and high hypoglycemia risk, respectively.

CONCLUSIONS: Optimizing deintensification requires patient education that describes both individualized glycemic targets and how they will change over the lifespan. Deintensification is an opportunity for shared decision-making, but providers must understand patients' beliefs about their medications and address misconceptions. Hypoglycemia prevention may be a helpful framing for discussing deintensification.

PMID:36175758 | DOI:10.1007/s11606-022-07828-3

Clin Drug Investig. 2022 Sep 30. doi: 10.1007/s40261-022-01202-1. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used as adjunctive therapy to lifestyle intervention and metformin treatment in type 2 diabetes mellitus patients, as most GLP-1RAs have cardiovascular benefits; however, a number of adverse events (AEs) have been reported in postmarketing surveillance.

OBJECTIVE: The aim of this study was to describe the AEs associated with GLP-1RA monotherapy and identify important medical event (IME) signals for GLP-1RAs.

METHODS: Data from 1 April 2005 to 31 December 2021 from the US FDA Adverse Event Reporting System (FAERS) database were extracted to conduct disproportionality analysis and Bayesian analysis. AEs and IMEs were classified by system organ classes (SOCs) and preferred terms (PTs) according to the Medical Dictionary for Regulatory Activities (MedDRA®). The reporting odds ratio (ROR) and information component (IC) were used to indicate the disproportionality.

RESULTS: A total of 71,515 records involving GLP-1RA monotherapy were submitted to the database, of which 16,350 records were GLP-1RA/IME pairs. Significant disproportionality emerged in five SOCs: 'gastrointestinal disorders' (n = 13,104; lower end of the 95% confidence interval (CI) of the IC [IC025] = 1.34), 'investigations' (n = 6889; IC025 = 0.64), 'metabolism and nutrition disorders' (n = 2943; IC025 = 0.44), 'neoplasms benign/malignant' (n = 1989; IC025 = 0.01), and 'hepatobiliary disorders' (n = 1497; IC025 = 0.38). The most common AEs were pancreatitis, nausea, and weight decrease. Unexpected significant AEs were detected, such as ileus, osteomyelitis, renal cell carcinoma, nephrolithiasis, and drug-induced liver injury.

CONCLUSION: The majority of AEs have been listed in the prescribing information or reported in previous studies, however we found significant disproportionality in some specific tumor- and liver-related AEs. Clinicians should pay more attention to the newly detected disproportionality that may be triggered by GLP-1RAs, especially in the vulnerable population after long-term use. Considering the limitations of the FAERS database, there is a need for additional pharmacoepidemiological approaches to validate the results of this study.

PMID:36175609 | DOI:10.1007/s40261-022-01202-1

Front Pharmacol. 2022 Sep 12;13:995439. doi: 10.3389/fphar.2022.995439. eCollection 2022.

ABSTRACT

Autism spectrum disorder (ASD) is characterized by high heritability and clinical heterogeneity. The main core symptoms are social communication deficits. There are no medications approved for the treatment of these symptoms, and medications used to treat non-specific symptoms have serious side effects. To identify potential drugs for repurposing to effectively treat ASD core symptoms, we studied ASD risk genes within networks of protein-protein interactions of gene products. We first defined an ASD network from network-based analyses, and identified approved drugs known to interact with proteins within this network. Thereafter, we evaluated if these drugs can change ASD-associated gene expression perturbations in genes in the ASD network. This was done by analyses of drug-induced versus ASD-associated gene expression, where opposite gene expression perturbations in drug versus ASD indicate that the drug could counteract ASD-associated perturbations. Four drugs showing significant (p < 0.05) opposite gene expression perturbations in drug versus ASD were identified: Loperamide, bromocriptine, drospirenone, and progesterone. These drugs act on ASD-related biological systems, indicating that these drugs could effectively treat ASD core symptoms. Based on our bioinformatics analyses of ASD genetics, we shortlist potential drug repurposing candidates that warrant clinical translation to treat core symptoms in ASD.

PMID:36172193 | PMC:PMC9510394 | DOI:10.3389/fphar.2022.995439

Cureus. 2022 Aug 25;14(8):e28394. doi: 10.7759/cureus.28394. eCollection 2022 Aug.

ABSTRACT

Clopidogrel is an antithrombotic agent widely used for the secondary prevention of cerebrovascular and cardiovascular complications. Clopidogrel can cause serious adverse events, including gastrointestinal bleeding. Pulmonary complications caused by clopidogrel are not widely described, and clopidogrel-induced interstitial lung disease (ILD) is rare. Here, we report a case of drug-induced ILD in a patient who presented with dyspnea, chest pain, and mild fever. The patient underwent percutaneous coronary intervention two months ago and was commenced on clopidogrel. He was diagnosed with clopidogrel-induced ILD based on clinical and imaging findings, history of drug exposure without any change, exclusion of other respiratory disorders, and clinical improvement after discontinuation of clopidogrel and steroid use.

PMID:36171842 | PMC:PMC9508896 | DOI:10.7759/cureus.28394

J Pediatr Gastroenterol Nutr. 2022 Sep 29. doi: 10.1097/MPG.0000000000003630. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients.

METHODS: We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments and related AE. We analysed the frequency, type, and risk factors for AE necessitating drug discontinuation.

RESULTS: A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn's disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least one drug-related AE that required drug cessation. Immunomodulators (methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)) followed by tumor necrosis factor (TNF)-alpha antagonists (adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)) accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE (OR = 2.50, 95%CI [1.50-4.17]) in all pediatric IBD patients.

CONCLUSIONS: Drug-related AE necessitating discontinuation are common in pediatric and adolescent inflammatory bowel disease patients. Caution needs to be taken in the case of concomitant drug use.

PMID:36171635 | DOI:10.1097/MPG.0000000000003630

Sci Rep. 2022 Sep 27;12(1):16131. doi: 10.1038/s41598-022-19884-0.

ABSTRACT

Under-reporting of adverse drug events (ADEs) is a challenge facing developing countries including Tanzania. Given the high magnitude of under-reporting, it was necessary to develop and assess the effectiveness of a 'structured stimulated spontaneous safety monitoring' (SSSSM) reporting program of ADEs which aimed at strengthening pharmacovigilance system in Tanzania. A quasi-experimental design and data mining technique were used to assess the effect of intervention after the introduction of program in seven tertiary hospitals. ADEs reports were collected from a single group and compared for 18 months before (July 2017 to December, 2018) and after the program (January 2019 to June 2020). Out of 16,557 ADEs reports, 98.6% (16,332) were reported after intervention and 0.1% (23) death related to adverse drug reactions (ADRs) were reported. Reports increased from 20 to 11,637 after intervention in Dar es salaam, 49 to 316 in Kilimanjaro and 17 to 77 in Mbeya. The population-based reporting ratio per 1,000,000 inhabitants increased from 2 reports per million inhabitants in 2018 to 85 reports in 2019. The SSSSM program can increase the reporting rate of ADEs and was useful in detecting signals from all types of medicines. This was first effective developed spontaneous program to monitor medicine safety in Tanzania.

PMID:36167960 | DOI:10.1038/s41598-022-19884-0

Cad Saude Publica. 2022 Sep 23;38(8):e00291221. doi: 10.1590/0102-311XPT291221. eCollection 2022.

ABSTRACT

Adverse drug events (ADEs) are harmful events caused by medication, and some of which can lead to death. Death records are an important source of information when using codes from the 10th revision of the International Classification of Diseases (ICD-10) suggestive of ADE. This study aimed to identify the ADEs registered in Brazililian Mortality Information System (SIM), analyzing data distribution by year, age group, and type of event. This is an ecological study with retrospective data collection, identifying ADEs in the SIM, using the ICD-10 codes. The study included deaths that occurred in Brazil from 2008 to 2016. An increase in the number of deaths associated with ADE was observed from 2008 to 2016, with a mortality rate per 1 million inhabitants ranging from 8.70 to 14.40 in the period. Most events corresponded to mental and behavioral disorders due to the use of psychotropic drugs. Most deaths (12,311) related to ADE codes were identified in several chapters of the ICD-10. Chapter XX, about adverse events, allowed the identification of a smaller number of deaths (4,893). Higher event rates were observed among individuals aged 60 years and over (39.8/1 million) and children younger than one year (22.0/1 million). The identification of ADE-related deaths on the SIM is an important strategy for addressing undesirable drug-related events. Deaths related to the use of psychotropic drugs were the most frequent ADE-related deaths and the elderly were the age group most affected by ADEs.

PMID:36169445 | DOI:10.1590/0102-311XPT291221

Expert Rev Anti Infect Ther. 2022 Sep 28. doi: 10.1080/14787210.2022.2128766. Online ahead of print.

ABSTRACT

BACKGROUND: Long-term outcome data from real-world studies on the implementation of a two-drug dolutegravir plus lamivudine (DTG+3TC) regimen for the treatment of human immunodeficiency virus (HIV) infection remain limited. This study evaluated the real-world effectiveness and safety of DTG+3TC in people living with HIV (PLHIV) in Southwestern China.

METHODS: This was an observational, single-center, retrospective study that enrolled antiretroviral therapy (ART)-naïve (n = 36) and ART-experienced patients with HIV (n = 86) between January 2019 and April 2021. The virological response to therapy and adverse events were documented. The primary endpoint was an HIV viral load (VL) <50 copies/mL at week 48.

RESULTS: The proportion of treatment-naïve and ART-experienced PLHIV with a VL <50 copies/mL at 48 weeks was 97.2% and 97.7%, respectively. The CD4 count increased significantly by 80.2 cells/μL (P = 0.012) and 79.0 cells/μL (P = 0.021) in the ART-naïve and ART-experienced patients, respectively. No patients discontinued DTG+3TC by week 48 due to adverse events.

CONCLUSION: Virologic suppression may be achieved with DTG+3TC, in ART-naïve patients with a high VL, and in ART-experienced patients with residual viremia. This study also demonstrated a low prevalence of drug-related side effects.

PMID:36168914 | DOI:10.1080/14787210.2022.2128766

Korean J Fam Med. 2022 Sep;43(5):290-295. doi: 10.4082/kjfm.21.0193. Epub 2022 Sep 20.

ABSTRACT

Pharmacovigilance is used to detect, assess, understand, and prevent the adverse effects of medications. The need for safety monitoring has evolved around unfortunate incidents in history, with deaths caused by anesthesia and congenital malformations from thalidomide use. Reports from adverse drug reactions (ADRs) are stored in a global database and can be used to evaluate the associations between various medications and associated ADRs. Clinicians play an important role in the recognition and reporting of ADRs to national pharmacovigilance centers (NPCs). The purpose of NPCs is to make the clinicians understand their functions, including the monitoring, investigation, and assessment of ADR reports, along with periodical benefit-risk assessments of medications via multiple sources. A case study on NPCs and the types of safety issues evaluated by them are provided to illustrate their role in medicine safety surveillance. ADR monitoring was also combined with vaccine safety surveillance approaches. Overall, this study will provide insights to clinicians on the importance of pharmacovigilance in maintaining patient safety with the proper use of medications.

PMID:36168900 | DOI:10.4082/kjfm.21.0193

Sci Rep. 2022 Sep 27;12(1):16112. doi: 10.1038/s41598-022-19729-w.

ABSTRACT

To alleviate anti-cancer treatment burden in advanced breast cancer, patient-clinician communication strategies based on nocebo-effect mechanisms are promising. We assessed distinct/combined effects on psychological outcomes (e.g. anxiety; main outcome) and side-effect expectations of (1) nocebo information about the (non)pharmacological origin of side effects, and (2) clinician-expressed empathy through reassurance of continuing support. Furthermore, we explored whether information and empathy effects on side-effect expectations were mediated by decreased anxiety. In a two-by-two experimental video-vignette design, 160 cancer patients/survivors and healthy women watched one of four videos differing in level of nocebo information (±) and empathy (±). Regression and mediation analysis were used to determine effects of information/empathy and explore anxiety's mediating role. Anxiety was not influenced by empathy or information (Stai-state: p = 0.295; p = 0.390, VAS p = 0.399; p = 0.823). Information improved (specific) side-effect coping expectations (p < 0.01). Empathy improved side-effect intensity expectations (p < 0.01 = specific; p < 0.05 = non-specific/partial) and specific side-effect probability expectations (p < 0.01), and increased satisfaction, trust, and self-efficacy (p < 0.001). No mediating effects were found of anxiety on expectations. Mainly empathy, but also nocebo information improved psychological outcomes and-mainly specific-side-effect expectations. Exploring the power of these communication elements in clinical practice is essential to diminish the anti-cancer treatment burden in advanced breast cancer.

PMID:36167876 | DOI:10.1038/s41598-022-19729-w

Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S353. doi: 10.1016/S2152-2650(22)01490-2.

ABSTRACT

CONTEXT: High-dose methotrexate (HDMTX) is commonly used for solid malignancies, such as osteosarcoma, and hematological malignancies, such as acute lymphoblastic leukemia and non-Hodgkin lymphoma. Urine alkalinization using intravenous sodium bicarbonate and MTX clearance with calcium folinate are two crucial steps in MTX clearance and avoiding or minimizing side effects, such as nephrotoxicity and hepatotoxicity.

OBJECTIVE: To assess the safety of ambulatory HDMTX administration among adult patients with hematological malignancies in a tertiary care center.

DESIGN: This is an open-label, single-arm trial that aims to evaluate the safety of HDMTX administration in an outpatient setting among patients with hematological malignancies.

SETTING: Tertiary care center.

PATIENTS OR OTHER PARTICIPANTS: The study was IRB approved.

INCLUSION CRITERIA: Adult patients from 14 to 60 years of age; normal baseline kidney and liver function; cooperative and fully compliant; living nearby the hospital with access to medical services.

EXCLUSION CRITERIA: Pregnant or breastfeeding women.

INTERVENTIONS: Urine alkalinization with sodium bicarbonate and acetazolamide, as per protocol, was started the day prior to MTX infusion. The patients were well hydrated and their serum MTX was measured daily until it fell below 0.1 micromol/L.

MAIN OUTCOME MEASURES: The safety of ambulatory HDMTX administration.

RESULTS: Forty-three (n=43) cycles for 21 patients have been completed thus far. Approximately 72.09% of cycles were for patients diagnosed with diffuse large B-cell lymphoma. Twenty-one (48.84%) cycles achieved MTX levels less than 0.1 micromol/L by 48 hours, and 39 cycles (90.70%) achieved the same level by 72 hours. By 72 hours, 23.26% had reversible, asymptomatic elevation of creatinine and all were Grade 1. By 72 hours, approximately 27.91% had reversible, asymptomatic hepatotoxicity and all were Grade 1.

CONCLUSIONS: Our preliminary results suggest that ambulatory HDMTX is safe, cost effective, and more comfortable for patients. These results encourage the use of this approach more frequently as it decreases hospitalization and thus reduces cost, increases patient satisfaction, and helps to solve the issue of bed crisis.

PMID:36164039 | DOI:10.1016/S2152-2650(22)01490-2

Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S345. doi: 10.1016/S2152-2650(22)01475-6.

ABSTRACT

CONTEXT: Bleomycin pulmonary toxicity (BPT) is a serious and potentially fatal complication of bleomycin, a key component of Hodgkin lymphoma (HL) treatment. Before ours, only one published study evaluated the predictability of FDG-PET/CT in the diagnosis of BPT.

OBJECTIVE: We aimed to determine whether FDG-PET/CT changes correlate with clinical BPT. Additionally, we assessed the correlation of clinical BPT with sociodemographic and disease characteristics.

DESIGN AND ANALYSIS: In this retrospective study, FDG-PET/CT scans of adult (age >18 years) HL patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) at a single urban academic center, University of Cincinnati Medical Center, from 2012 to 2016 were evaluated for pulmonary toxicity and then assessed for the development of clinical BPT. The images were evaluated by 2 separate radiologists, for whom the clinical information was anonymized. All P-values were two-sided; P<0.05 was considered statistically significant. Data were analyzed using SAS 9.4 software.

RESULTS: We found 54 FDG-PET/CT scans from 11 patients who received bleomycin for HL. Five of the 11 (45%) patients had radiographic changes that were characteristically focal or diffuse opacities on PET/CT and developed clinical BPT. One patient had radiological changes but did not develop clinical BPT, whereas the other five had no signs of toxicity on imaging. Patients with clinical BPT had higher SUVmax than those without (mean [CI] 2.66 [1.8-3.7] vs. 0.86 [0.4-1.9], P<0.05, Mann-Whitney U test). In a separate analysis, we compared patients with clinical BPT (9/25, 36%) and without (16/25, 64%). Patients with clinical BPT had lower hemoglobin (mean 10.9 vs. 13.3 g/dL, P=0.037) and higher ESR (mean 63.3 vs. 30.2 mm/hr, P=0.0289). We found that gender, stage, histology, history of lung radiation, prior G-CSF, and steroids did not significantly confer a higher risk of BPT. Patients with bulky disease and prior lung disease had a higher risk of clinical BPT; however, the correlation was not statistically significant.

CONCLUSIONS: We conclude that FDG-PET/CT imaging, which is routinely used to assess treatment response in HL, is useful for early detection and guiding interventions for BPT. Hemoglobin and ESR at diagnosis can be predictive of BPT; further studies are needed.

PMID:36164024 | DOI:10.1016/S2152-2650(22)01475-6

Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S292-S293. doi: 10.1016/S2152-2650(22)01374-X.

ABSTRACT

CONTEXT: Chronic myeloid leukemia (CML) is treated with the first-line agent imatinib; however, it was seen that adherence to treatment had been poor in many patients. Therefore, a study was carried out to find causative reasons for the discontinuation of treatment, with the ultimate goal to improve rates of compliance.

OBJECTIVE: The aim of the study was to identify reasons for adherence failure in patients treated with imatinib for CML and to detect a way to improve adherence.

METHODS: A prospective review of 160 patients with newly diagnosed Philadelphia chromosome-positive CML was undertaken to check for rates of adherence to treatment with imatinib. The patients were equally distributed with 77 men and 83 women and had an average age of 40 years. Due to imatinib being the only option for most patients in India for CML, those who discontinued it were reinforced about the importance of being compliant with treatment. The rates of patients who restarted imatinib after reinforcement were recorded.

RESULTS: It was found that out of 160 patients over the initial year of treatment, 87 patients (54.3%) continued to take imatinib and 73 patients (45.6%) discontinued treatment. The most common reasons for discontinuation of treatment were due to adverse drug events such as headaches, weight gain, musculoskeletal symptoms, and GI disturbances. Of the 73 patients, 60 (82.3%) stopped taking imatinib due to adverse drug events, 10 (13.6%) patients were lost to follow-up, and 3 (4.1%) patients wanted to pursue holistic methods of treatment. The 60 patients who stopped taking imatinib due to adverse drug events were counseled on the benefits of pursuing treatment despite some adverse effects. Out of the 60 patients who stopped imatinib due to adverse effects after counseling, 43 (71.6%) patients restarted imatinib.

CONCLUSIONS: The patients' adherence to imatinib in our study was found to be 46%, with the majority of patients discontinuing treatment due to adverse effects. However, after counseling patients on the overall benefits of taking imatinib, compliance improved. The authors believe that compliance can be improved by taking the time to educate patients on the benefits of treatment with reinforcement.

PMID:36163920 | DOI:10.1016/S2152-2650(22)01374-X

Drug Ther Bull. 2022 Sep 27:dtb-2022-000046. doi: 10.1136/dtb.2022.000046. Online ahead of print.

NO ABSTRACT

PMID:36167660 | DOI:10.1136/dtb.2022.000046

Infect Drug Resist. 2022 Sep 19;15:5483-5494. doi: 10.2147/IDR.S381715. eCollection 2022.

ABSTRACT

PURPOSE: Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia.

METHODS: It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group "ivermectin group" included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients "placebo group" who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done.

RESULTS: The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05.

CONCLUSION: In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment.

TRIAL REGISTRATION NO: NCT04951362.

PMID:36164334 | PMC:PMC9508858 | DOI:10.2147/IDR.S381715