Phase I trial of 131I-GMIB-Anti-HER2-VHH1, a new promising candidate for HER2-targeted radionuclide therapy in breast cancer patients.

J Nucl Med. 2020 Dec 04;:

Authors: D'Huyvetter M, De Vos J, Caveliers V, Vaneycken I, Heemskerk J, Duhoux FP, Fontaine C, Vanhoeij M, Windhorst AD, van der Aa F, Hendrikse NH, Eersels JLE, Everaert H, Gykiere P, Devoogdt N, Raes G, Lahoutte T, Keyaerts M

Abstract
Introduction: 131I-GMIB-Anti-HER2-VHH1 is a targeted radionuclide theranostic agent directed at HER2 expressing cancers. VHH1 is a single domain antibody fragment covalently linked to therapeutic radio-iodine 131I via the linker SGMIB. The Phase I study presented was aimed at evaluating the safety, biodistribution, radiation dosimetry and tumor imaging potential of 131I-GMIB-Anti-HER2-VHH1 in healthy volunteers and breast cancer patients. Methods: In a first cohort, six healthy volunteers were included. The biodistribution of 131I-GMIB-Anti-HER2-VHH1 was assessed using whole body (anterior and posterior) planar images obtained at 40 min., 2, 4, 24 and 72 h following i.v. administered (38 ± 9 MBq) 131I-GMIB-VHH1. Imaging data were analyzed using OLINDA/EXM software 1.0 to determine the dosimetry. Blood and urine samples were obtained over 72h. In the second cohort, three patients with metastatic HER2 positive breast cancer were included. Planar whole-body imaging was performed at 2 h and 24 h after injection. Additional SPECT/CT images were obtained following the whole body images at 2 and 24 h in case of relevant uptake in known cancer lesions Results: No drug related adverse events (AEs) were observed throughout the study. The biological half-life of 131I-GMIB-Anti-HER2-VHH1 in healthy subjects was about 8 h. After i.v. administration, the compound is eliminated from the blood with a 2.5 h half-life. The drug is primarily eliminated via the kidneys. The drug was stable in circulation and there was no increased accumulation in thyroid or stomach. The absorbed dose to the kidneys was 1.54 ± 0.25 mGy/MBq, while to bone marrow 0.03 ± 0.01 mGy/MBq. SPECT/CT imaging in patients with advanced breast cancer showed focal uptake of 131I-GMIB-Anti-HER2-VHH1 in metastatic lesions. Conclusion: No AEs were observed after iv administration of 131I-GMIB-Anti-HER2-VHH1 at low activity. Unbound drug is rapidly eliminated via the kidneys. In patients with stage IV HER2 positive breast cancer accumulation of 131I-GMIB-Anti-HER2-VHH1 in metastatic sites was observed. Dosimetry predicts kidneys as the dose limiting organ upon dose escalation, but kidney toxicity should only occur at very high injected activities. Dose escalation is planned in a subsequent phase I/II study to assess the therapeutic window of this compound (NCT04467515).

PMID: 33277400 [PubMed - as supplied by publisher]

Palliative- and non-palliative indications for glucocorticoids use in course of immune-checkpoint inhibition. Current evidence and future perspectives.

Crit Rev Oncol Hematol. 2020 Nov 17;157:103176

Authors: Marinelli D, Giusti R, Mazzotta M, Filetti M, Krasniqi E, Pizzuti L, Landi L, Tomao S, Cappuzzo F, Ciliberto G, Barba M, Vici P, Marchetti P

Abstract
Immune-checkpoint inhibitors significantly reshaped treatment landscapes in several solid tumors. Concurrently with disease-oriented therapies, cancer patients often require proper management of drug-related adverse events and/or cancer-related symptoms. Glucocorticoids (GC) are a cornerstone of symptom management in advanced cancer care and in the management of immune-related adverse events (irAEs) due to immune-modulating therapies. Moreover, GC are often administered in patients with autoimmune diseases (AID), either alone or in combination with other treatments. While handling of irAEs with GC is supported by multiple guidelines, it is unclear whether GC administration because of pre-existing AID or because of palliative needs is associated with inferior outcomes in cancer patients treated with immune-checkpoint inhibitors (ICIs). When globally considered, the available evidence seems to orient towards less favorable survival outcomes when GC administration is driven by a palliative intent. Conversely, steroid administration for non-palliative intent seems to be associated with stable or negligibly reduced survival outcomes.

PMID: 33276183 [PubMed - as supplied by publisher]

Immunosuppressant-induced cutaneous drug reactions in solid organ transplant recipients.

Transpl Immunol. 2020 Nov 29;:101355

Authors: Miotto IZ, de Castro E Souza B, Tyring SK, de Oliveira WRP

Abstract
Solid organ transplant recipients (SOTRs) are susceptible to various cutaneous side effects as a consequence of long-term immunosuppressive therapy. Skin cancers and infections are well-studied complications that can cause death and/or allograft rejection. Other cutaneous drug reactions, such as inflammatory manifestations, have a high prevalence but are rarely studied. We analyzed these manifestations' prevalence and their association with immunosuppressants in transplant recipients from a Brazilian tertiary center. Among 532 SOTRs followed at our dermatology clinic, 60 (11.3%) developed some cutaneous adverse reactions to the immunosuppressants, with a median age at transplantation of 50.5 years and a median life span posttransplantation of seven years. Acneiform eruption was the most common drug reaction found (21 patients, 30.4%), followed by diffuse non-scarring alopecia (16 patients, 23.1%), lymphedema (10 patients, 14.5%), gingival hyperplasia (7 patients, 10.1%), hypertrichosis (6 patients, 8.7%) and sebaceous hyperplasia (9 patients, 13.1%). Adequate immunosuppression is an essential prerequisite for successful organ transplantation. In the immediate post-transplant period, significant immunosuppression is needed, but after that, the complications of excessive immunosuppression outweigh the risk of organ rejection. SORTs may present with a broad spectrum of inflammatory and cosmetic findings due to immunosuppressants that can impair life quality.

PMID: 33264680 [PubMed - as supplied by publisher]

Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score.

BMC Geriatr. 2020 09 14;20(1):346

Authors: Danjuma MI, Almasri H, Alshokri S, Khir FK, Elmalik A, Battikh NG, Abdallah IMH, Elshafei M, Fatima H, Mohamed MFH, Maghoub Y, Hussain T, Kamal I, Anwer Z, Bidmos MA, Elzouki AN

Abstract
BACKGROUND: Drug-induced liver injury (DILI) represents an increasing morbidity in the general population, but more so in the elderly cohort of patients. Despite this, the concept of its prevention through prospective analysis has largely remained unexamined. We evaluated the utility of recently validated adverse drug reactions (ADR) avoidability tool in a cohort of elderly patients with DILI.
METHODS: We examined 38 DILI-drug pairs from n=38 patients in a prospective cohort of patients presenting with adverse drug reactions to a Weill Cornell-affiliated tertiary hospital between February 2019 and January 2020. DILI outcomes were adjudicated by the updated Roussel Uclaf Causality Assessment Method (RUCAM). Two clinical pharmacologists and two general physicians utilized the Liverpool adverse drug reactions avoidability tool (LAAT) and the modified Hallas tools to rate the preventability of DILI-drug pairs. Inter-rater, exact agreement proportions, as well as intraclass correlation coefficients were generated and expressed as ordinal outcomes.
RESULTS: The cases examined for the determination of DILI avoidability had probability likelihood of "probable" or "highly probable" by the updated RUCAM scale. Examination of the 38 DILI-drug pairs (n= 38 patients) resulted in a total of 152 ordinal outcome decisions. We found about 32.3% (50/152) and 34.2% (52/152) of DILI-drug pairs were rated as "avoidable" ("probable" or "definite") by the LAAT and the modified Hallas tools respectively. The overall median Krippendorf's kappa with the LAAT was 0.61 (SE 0.12, CI 0.36, 0.85) and for modified Hallas tool was 0.53 (SE 0.18; CI 0.16, 0.89). The inter-rater correlation coefficient (ICC) for the LAAT and modified Hallas were 0.50 [0.32, 0.65] and 0.63 [0.48, 0.76] respectively. Exact pairwise agreement was present in 30/38 (IQR 29.5, 34.5), and 28/38 (IQR 27.5-35.5) of DILI-ADR pairs using the LAAT and modified Hallas tools respectively.
CONCLUSION: We found a significant proportion of drug-induced liver injury adjudicated by the updated RUCAM scale in elderly hospitalized cohort of patients were avoidable with significant implication for therapeutic commissioning as well as cost effectiveness interventions in this cohort of patients.

PMID: 32928134 [PubMed - indexed for MEDLINE]

Polypharmacy in three different spontaneous adverse drug event databases.

Int J Clin Pharmacol Ther. 2020 Nov;58(11):601-607

Authors: Mabuchi T, Hosomi K, Yokoyama S, Takada M

Abstract
OBJECTIVE: Polypharmacy has become a major problem in medical care worldwide, including in Japan. The purpose of this study was to investigate the current situation of polypharmacy using different spontaneous adverse drug event report databases.
MATERIALS AND METHODS: A retrospective data analysis was performed using reports from 2007 to 2015 from three different spontaneous adverse drug event report databases: the Japanese Adverse Drug Event Report (JADER) constructed by the Pharmaceuticals and Medical Devices Agency in Japan, the US Food and Drug Administration (FDA) Adverse Drug Event Reporting System (FAERS) constructed by the FDA in the United States, and the Canada Vigilance Adverse Reaction Online Database (CVARD) constructed by the government of Canada. Polypharmacy trends during the study period were investigated.
RESULTS: The mean numbers of drugs per report in the JADER, FAERS, and CVARD databases during the study period were 6.62, 3.76, and 3.44, respectively. The mean number of drugs per report increased with age in all three databases, with a peak at ages 70 - 79 years in all three databases (7.0 drugs for JADER, 4.7 drugs for FAERS, and 4.2 drugs for CVARD).
CONCLUSION: Adverse event reports were more likely to develop in the patients treated through polypharmacy. Polypharmacy in Japan should be improved to prevent adverse events. Additionally, the patients aged ≥ 80 years tended to develop adverse events even if the number of prescribed drugs was relatively small. Therefore, polypharmacy should be noted in these patients to prevent adverse events.

PMID: 32729825 [PubMed - indexed for MEDLINE]

Cardiovascular pharmacotherapy in older people: challenges posed by cardiovascular drug prescription in the elderly.

Eur Heart J Cardiovasc Pharmacother. 2020 09 01;6(5):277-279

Authors: Kaski JC, Tamargo J, Savarese G

PMID: 32687147 [PubMed - indexed for MEDLINE]

Mechanistic basis for PI3K inhibitor antitumor activity and adverse reactions in advanced breast cancer.

Breast Cancer Res Treat. 2020 Jun;181(2):233-248

Authors: Drullinsky PR, Hurvitz SA

Abstract
PURPOSE: The phosphatidylinositol 3-kinase (PI3K) pathway is involved in several physiological processes, including glucose metabolism, cell proliferation, and cell growth. Hyperactivation of this signaling pathway has been associated with tumorigenesis and resistance to treatment in various cancer types. Mutations that activate PIK3CA, encoding the PI3K isoform p110α, are common in breast cancer, particularly in the hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) subtype. A number of PI3K inhibitors have been developed and evaluated for potential clinical use in combinations targeting multiple signaling pathways in cancer. The purpose of this review is to provide an overview of PI3K inhibitor mechanisms of action for antitumor activity and adverse events in advanced breast cancer (ABC).
METHODS: Published results from phase 3 trials evaluating the efficacy and safety of PI3K inhibitors in patients with ABC and relevant literature were reviewed.
RESULTS: Although PI3K inhibitors have been shown to prolong progression-free survival (PFS), the therapeutic index is often unfavorable. Adverse events, such as hyperglycemia, rash, and diarrhea are frequently observed in these patients. In particular, hyperglycemia is intrinsically linked to the inhibition of PI3Kα, a key mediator of insulin signaling. Off-target effects, including mood disorders and liver toxicity, have also been associated with some PI3K inhibitors.
CONCLUSION: Recent clinical trial results show that specifically targeting PI3Kα can improve PFS and clinical benefit. Broad inhibition of class I PI3Ks appears to result in an unfavorable safety profile due to off-target effects, limiting the clinical utility of the early PI3K inhibitors.

PMID: 32274666 [PubMed - indexed for MEDLINE]

Do cancer therapies damage the uterus and compromise fertility?

Hum Reprod Update. 2020 02 28;26(2):161-173

Authors: Griffiths MJ, Winship AL, Hutt KJ

Abstract
BACKGROUND: As cancer survival rates improve, understanding and preventing the adverse off-target and long-term impacts of cancer treatments, including impacts on fertility, have become increasingly important. Cancer therapy-mediated damage to the ovary and depletion of the primordial follicle reserve are well characterised. However, our knowledge of the full extent of damage to the rest of the female reproductive tract, in particular the uterus, is limited.
OBJECTIVE AND RATIONALE: Improving our understanding of the off-target effects of cancer therapies on the entire female reproductive tract is a critical step towards developing truly effective strategies to protect the fertility of cancer survivors. The objective of this narrative review was to critically evaluate the available literature regarding the capacity for the uterus to sustain a healthy pregnancy following exposure to radiotherapy or chemotherapy.
SEARCH METHODS: The authors performed PubMed (Medline) searches using the following key words: uterus, cancer survivors, radiotherapy, chemotherapy, pregnancy outcome, fertility preservation, infertility. There were no limits placed on time of publication.
OUTCOMES: Overall, there were major limitations to the current available literature, meaning that interpretations should be taken with caution. Despite these drawbacks, data suggest that the uterus may sustain off-target damage, with the extent of damage dependent on the type of cancer treatment and patient age. Specifically, uterine growth is stunted and resistant to hormone replacement therapy in prepubertal girls receiving abdominal, pelvic or whole-body radiotherapy. In contrast, females treated with radiotherapy post-puberty can benefit from hormone replacement therapy, as demonstrated by increased uterine volume and function. No live births have been reported in women previously exposed to radiotherapy after transplantation of cryopreserved ovarian tissue, even when menstruation returns. However, this technique has proven to be a successful fertility preservation method for women previously treated with chemotherapy. Obstetricians commonly report that women who maintain sufficient ovarian function can achieve pregnancy naturally following radiotherapy, but they have thin and/or fibrotic myometrium at delivery, compromising safe delivery and subsequent pregnancy. Furthermore, women exposed to either radiotherapy or chemotherapy have a higher prevalence of preterm birth and low birth weight infants, even in those with normal ovarian function or when oocyte donation is utilised. The mechanisms of potential uterine damage are poorly understood. While the myometrium, vasculature and endometrial progenitor cells are possibly targets, further studies are clearly required and well-controlled animal models could provide the best avenue for these types of future investigations.
WIDER IMPLICATIONS: Female cancer survivors experience greater rates of early pregnancy loss and complications, suggesting that cancer therapy-induced damage to the uterus contributes to infertility. Despite clinical reports dating back to 1989, we highlight a surprising lack of detail in the literature regarding the precise nature and extent of off-target damage inflicted to the uterus in response to cancer therapies. Young women requiring cancer treatment, and the clinicians treating them, must be equipped with accurate information to aid informed decision-making regarding cancer treatment regimens as well as the development and use of effective fertility preservation measures. As the current literature on the impacts of cancer treatments is limited, we hope that our narrative review on this subject will stimulate more research in this important field.

PMID: 31863097 [PubMed - indexed for MEDLINE]

Impact of transitioning inpatient chemotherapy regimens to the outpatient setting.

J Oncol Pharm Pract. 2020 Sep;26(6):1324-1330

Authors: Corsi MP, Shea K, W Knoebel R

Abstract
BACKGROUND: Chemotherapy regimens historically have required admission of the patient to the hospital for extended infusions running over multiple days to complete each cycle of therapy. With the evolution of monitoring strategies readily available, a renaissance in patient care and healthcare cost utilization is necessary as transitioning the administration of these agents to the outpatient setting is seemingly achievable and is potentially more cost-effective.
PURPOSE: This evaluation sought to primarily measure cost-savings for an institution by transitioning inpatient chemotherapy regimens to the outpatient setting. Secondary outcomes evaluated the effect of this transition on overall patient length of stay, prevalence of adverse effects, and overall chemotherapy schedule adherence as a result of implementing transitions in sites of care. Barriers to receiving care in the outpatient setting were assessed by evaluating the acuity of performance status as well as distance from the hospital.
METHODS: This single-center retrospective, quantitative chart and expense analysis evaluated patients receiving rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) or rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) chemotherapy regimens based on treatment setting at a single institution. Included patients were treated at the University of Chicago Medical Center. Those receiving inpatient-only management as compared with patients who received therapy in outpatient settings were compared in a matched cohort analysis. The control group was matched from the period before transition of therapy was instituted between November 2014 and November 2015, with those patients transitioned to outpatient therapy (December 2015 to November 2016), using demographic, diagnostic, treatment, and clinical status data to assure group similarity. Mean cost of therapy was compared between inpatient and outpatient regimens. Descriptive and demographic categorical data were compared using the Fisher's exact test. Continuous data were evaluated using the Student's t test. A significance level of alpha <0.05 was used for all analysis.
RESULTS: The cost of R-EPOCH therapy represented a significant difference across groups. R-ICE therapy similarly saw significant cost differences between inpatient and outpatient groups. If this was made standard of care for qualifying patients a retrospective annualized estimation of $466,507.85 with R-EPOCH therapy and $205,977.60 for R-ICE therapy could have been saved if this was utilized for patients who previously received their therapy as an inpatient.
CONCLUSION: The population of patients cared for at the University of Chicago Medicine during this time-period qualified for outpatient treatment for those treated with R-EPOCH and R-ICE regimens with no significantly identifiable prohibitive barriers between groups. As no significant complications manifested, it is reasonable to continue transitioning patients receiving these regimens to the outpatient setting where appropriate. R-EPOCH and R-ICE therapies were shown to be reasonable outpatient therapy while providing significant cost-savings for the institution.

PMID: 31822200 [PubMed - indexed for MEDLINE]

Treatment Complexity in Primary Open-Angle Glaucoma (POAG): Perspectives on Patient Selection in Micro-Invasive Glaucoma Surgery (MIGS) Using Stents.

Klin Monbl Augenheilkd. 2020 Nov 30;:

Authors: Helbig C, Wollny A, Altiner A, Diener A, Kohlen J, Ritzke M, Frech S, Guthoff RF

Abstract
BACKGROUND: Primary open-angle glaucoma (POAG) is still one of the most common causes of impaired vision worldwide, despite the further development of therapy options, and can lead to blindness. Micro-invasive glaucoma surgery (MIGS) using stents aims at reducing intraocular pressure (IOP), as it is the main risk factor. With regard to adherence and adverse drug reactions it also aims at reducing the drug burden on patients. The study investigates under everyday conditions the criteria according to which ophthalmologists in Germany select patients for MIGS using stents. In addition, it will be investigated which patients (could) benefit most from the therapy.
MATERIAL AND METHODS: In this qualitative study, 11 narrative interviews were conducted between May 2017 and July 2018 with ophthalmologists working in the hospital or in a private practice. They were interviewed on their experiences in the treatment of POAG with microstents. The interviews were analysed by an interdisciplinary team using the qualitative content analysis.
RESULTS: The stages of therapy escalation form the frame of reference for patient selection in MIGS using stents. Only if the IOP cannot be sufficiently reduced by drop therapy or when this causes drug-related side effects that are intolerable for the patients, stents are apparently used as the next higher escalation stage. The intensive post-operative medication and the frequent check-up appointments are perceived as barriers by the interviewees, especially for people with or without disabilities, who are dependent on external help and/or those living in rural areas. The active cooperation of the patients in the demanding aftercare seems to be indispensable for the ophthalmologists. In addition, necessary revisions are sometimes stressful for patients (physical/psychological) and doctors (work organisation/therapy). Against the background of the organisational and economic challenges in the outpatient spectrum of tasks, especially physicians in private practice seem to weigh up carefully for which patients microstent therapy would be reasonable.
CONCLUSION: In view of the therapeutic requirements, the current microstent therapy seems to be used in a selected, adherent patient group. Further qualitative and quantitative studies (in other health care regions and structures) are necessary to verify and extend the available results.

PMID: 33254258 [PubMed - as supplied by publisher]

Direct antiviral drugs in the treatment of hepatitis C-infected rheumatoid arthritis Egyptian cohort: safety and clinical impact.

Eur J Gastroenterol Hepatol. 2020 Nov 30;:

Authors: Lashen SA, Metawea MI, Shaaban A

Abstract
BACKGROUND AND AIM: Data about the safety and efficacy of direct-acting antivirals (DAAs) in the treatment of hepatitis C virus (HCV) patients with concomitant rheumatoid arthritis (RA) are scarce. We assessed the impact and safety of DAAs treatment of hepatitis C on rheumatoid arthritis disease activity.
PATIENTS AND METHODS: Prospectively, we enrolled 65 patients with RA and HCV. A clinico-laboratory evaluation was done at baseline, including liver assessment and RA disease activity score-28 (DAS28). At 12 weeks of post-DAAs treatment, sustained virologic response (SVR12) and DAS28 were reevaluated.
RESULTS: The SVR12 was achieved in 59 (90.8%) patients. RA control was achieved in 47 (79.9%) patients. The post SVR12 DAS28 score was significantly lower than the baseline (3.32 ± 0.93 vs. 4.37 ± 0.90; P < 0.001). There was a significant decline in the mean values of serum anticyclic citrullinated peptide, rheumatoid factor, erythrocyte sedimentation rate and C-reactive protein after achieving an SVR12 (30.47 ± 12.37 vs. 57.61 ± 15.91 U/ml; 29.78 ± 19.58 vs. 55.14 ± 16.89 IU/ml; 17.13 ± 10.84 vs. 29.68 ± 14.32 mm/h and 5.76 ± 1.57 vs. 11.44 ± 4.13 mg/l, respectively; P < 0.05). RA activity and antirheumatic drugs were stepped-down [12 (20.3%) and 35 (59.3%) patients showed good and moderate RA response, respectively]. The baseline viral load, absence of cirrhosis and SVR12 were the only predictors of disease control (P < 0.05). No drug-related adverse events or drug-related discontinuation.
CONCLUSIONS: Unlike interferon, HCV elimination by DAAs significantly improves RA activity and treatment outcome with high safety and efficacy.

PMID: 33252421 [PubMed - as supplied by publisher]

A risk-stratified approach toward safely resuming OnabotulinumtoxinA injections based on dosing and ambulatory status in pediatric patients with cerebral palsy during the Coronavirus pandemic of 2019 (COVID-19).

J Pediatr Rehabil Med. 2020;13(3):273-279

Authors: McLaughlin MJ, Fisher MT, Vadivelu S, Ramsey J, Ratnasingam D, McGhee E, Hartman K

Abstract
PURPOSE: After the onset of the Coronavirus pandemic of 2019-2020 (COVID-19), physicians who inject OnabotulinumtoxinA (BoNT-A) were left with determining risks and benefits in pediatric patients with cerebral palsy. Many of these patients have pre-existing conditions that make them more prone to COVID-19 symptoms, and this susceptibility potentially increases after BoNT-A injections.
METHODS: A retrospective chart review of 500 patients identified 256 pediatric patients with cerebral palsy who received an intramuscular BoNT-A injection to determine relative doses used for each Gross Motor Functional Classification Score (GMFCS). Data regarding age, weight, GMFCS, BoNT-A total body dosage, and inpatient hospitalizations for 6 months post-injection were collected. Differences between GMFCS levels were analyzed using one-way analysis of variance testing. Inpatient hospitalizations were recorded and assessed using relative risk to determine the population risk of hospitalization in the setting of initiating injections during the COVID-19 pandemic.
RESULTS: Based on GMFCS level, patients who were GMFCS I or II received fewer units of BoNT-A medication per kilogram of body weight compared to GMFCS III-V (p< 0.0005, F= 25.38). There was no statistically significant difference in frequency or time to hospitalization when comparing patients receiving BoNT-A compared to a control group.
CONCLUSIONS: Resumption of BoNT-A injections during the time of COVID-19 requires a systematic approach based on risks and potential benefits. Data from this analysis does not show increased risk for patients who received injections historically; however, recommendations for resumption of injections has not previously been proposed in the setting of a pandemic. In this manuscript, a tiered approach to considerations for injections was proposed. Botulinum toxin type A injections have a history of improving spasticity in the pediatric patient with cerebral palsy. Ensuring appropriate selection of patients for injection with BoNT-A during this pandemic is increasingly important.

PMID: 33252098 [PubMed - in process]

The older patient presenting with itch and a recent medication change.

Aust J Gen Pract. 2020 05;49(5):276-279

Authors: Turner LM, Hwang SJE, Bennett G, Miller AC

PMID: 32416660 [PubMed - indexed for MEDLINE]

Therapeutic Characteristics, Chemotherapy-Related Toxicities and Survivorship in Colorectal Cancer Patients.

Ethiop J Health Sci. 2020 Jan;30(1):65-74

Authors: Aoullay Z, Slaoui M, Razine R, Er-Raki A, Meddah B, Cherrah Y

Abstract
Background: Colorectal Cancer (CRC) is a major health problem around the globe. In Morocco, the disease ranks third after breast and lung cancers. This study is the first in Morocco to investigate epidemiological, clinical and therapeutic features while exhaustively describing toxic side-effects to chemotherapy of CRC and studying the 3-years survivorship.
Methods: This is a descriptive and analytical retrospective study of about 290 patients with CRC enrolled during the period of January-December 2013. Statistical analysis was performed to correlate clinicopathological data with chemotherapy toxicity and survivorship in patients, by Chi2 test. Overall Survival (OS) rate has been calculated by the Kaplan-Meier method and compared using Log-rank test.
Results: Fifty-five percent had a tumor localized in rectum, and 42,8% in colon. Mean age of these patients at diagnosis was 56,16 ± 14,6. incidence rate of adverse events (grade I to IV) was 85,6%. Diarrhea was the predominant toxicity (4.6%) occurring at a high grade (grade III-IV).The 3-years OS rate of patients with CRC was 71%. OS decreased by age, and patients with age subgroup between 40 to 59 years had a better OS than the other age subgroups (60 to 79 years and >80 years) with a p-value of 0.0001. Occurence of toxicity (all grades and types) was linked to a higher survival rates compared to the group who had no toxicity noticed (p-value of 0.001).
Conclusion: Our study shows that patients who had a polychemotherapy had a better OS than those who had monotherapy (p-value of 0.002).

PMID: 32116434 [PubMed - indexed for MEDLINE]

Management of psoriasis-like rash associated with idelalisib monotherapy in a patient with refractory follicular lymphoma: a case report.

J Med Case Rep. 2020 Feb 24;14(1):35

Authors: Machan S, Plaza C, Pérez-González Y, Rodriguez-Pinilla M, Requena L, Cordoba R

Abstract
BACKGROUND: Follicular lymphoma is an indolent non-Hodgkin lymphoma that is most commonly diagnosed in elderly individuals. The majority of patients with follicular lymphoma present with advanced disease. Despite the recent advances in treatment, there remains a substantial unmet need for effective treatments for patients with relapsed/refractory follicular lymphoma. The PI3Kδ inhibitor idelalisib was approved by the European Medicines Agency in 2014 as a monotherapy for the treatment of adult patients with follicular lymphoma that is refractory to two prior lines of treatment. Real-world evidence from patients with follicular lymphoma treated with idelalisib indicates its utility in these patients.
CASE PRESENTATION: This case report describes an 82-year-old, retired, white, female patient with refractory follicular lymphoma who achieved a partial response with idelalisib treatment. Despite experiencing two incidences of a psoriasis-like rash during idelalisib treatment that required effective management with topical steroids, the patient was able to restart treatment successfully and maintain a continued partial response.
CONCLUSIONS: The clinical relevance of the effective management of adverse events in this case demonstrates the opportunity to enable patients to remain on therapy, thereby maintaining long-term response and improving overall outcomes.

PMID: 32093776 [PubMed - indexed for MEDLINE]

Comparison of Ketamine Alone and Subanesthetic Dose of Ketamine-Fentanyl for Regional Anesthesia in Children.

J Coll Physicians Surg Pak. 2020 Jan;30(1):102-103

Authors: Zhong L, Li H, Zhao B

PMID: 31931945 [PubMed - indexed for MEDLINE]

Diphtheria Antitoxin Administration, Outcomes, and Safety: Response to a Diphtheria Outbreak in Cox's Bazar Bangladesh.

Clin Infect Dis. 2020 Nov 27;:

Authors: Eisenberg N, Panunzi I, Wolz A, Burzio C, Cilliers A, Islam MA, Noor WM, Jalon O, Jannat-Khah D, Cuesta JG

Abstract
BACKGROUND: Diphtheria has re-emerged over the past several years. There is a paucity of data on the administration and safety of diphtheria antitoxin (DAT), the standard treatment for diphtheria. The 2017-2018 outbreak among Rohingya refugees in Bangladesh was the largest in decades. We determined the outcomes of DAT-treated patients and describe the occurrence and risk factors associated with adverse reactions to DAT.
METHODS: We conducted a retrospective study at the Médecins Sans Frontières Rubber Garden Diphtheria Treatment Center from December 2017-September 2018. Diphtheria was diagnosed based on the WHO clinical case criteria. High-acuity patients were eligible for DAT. Safety precautions were meticulously maintained. We calculated the presence of adverse events by age, duration of illness, and DAT dosage using bivariate comparisons.
RESULTS: We treated 709 patients with DAT. Ninety-eight percent (n=696) recovered and were discharged. One-fourth (n=170) had at least one adverse reaction. Common reactions included cough (n=115, 16%), rash (n=66, 9%), and itching (n=37, 5%). Three percent (n=18) had severe hypersensitivity reactions. Five patients died during their DAT infusion or soon afterwards, but no deaths were attributed to DAT.
CONCLUSIONS: The outcomes for DAT-treated patients were excellent; mortality was less than 1%. Adverse reactions occurred in a quarter of all patients, but most reactions were mild and resolved quickly. DAT can be safely administered in a setting with basic critical care, provided that there is a continuous patient monitoring during the infusion, staff training on management of adverse effects, and attention to safety precautions.

PMID: 33245364 [PubMed - as supplied by publisher]

Cost-effectiveness of baloxavir marboxil compared to laninamivir for the treatment of influenza in Japan.

J Infect Chemother. 2020 Nov 23;:

Authors: Skrzeczek A, Ikeoka H, Hirotsu N, Ansaripour A, Aballéa S, Onishi Y, Hill M, Igarashi A

Abstract
BACKGROUND: Baloxavir marboxil (baloxavir) is a new oral antiviral for influenza types A and B.
OBJECTIVES: To determine the cost-effectiveness of baloxavir versus laninamivir in otherwise healthy (OwH) adults in Japan.
METHODS: A decision tree was utilized to describe the course of influenza and predict associated costs and quality-adjusted life-years (QALYs) over one year by antiviral. Costs were valued from the public healthcare payer perspective, including influenza test, antiviral acquisition, other medications, physician visits, other outpatient costs associated with influenza or drug-related adverse events (DRAEs), and hospitalizations. Resource utilization and unit costs were obtained from the analysis of the JammNet claims database. Health state utilities were obtained from a clinical trial of baloxavir and previous models, and were driven by influenza symptoms, DRAEs, and complications caused by influenza. Sensitivity analyses were also performed.
RESULTS: The total payer expenditure per patient for baloxavir versus laninamivir was ¥9383 versus ¥9132. The additional acquisition costs of baloxavir were partly offset by the DRAE costs avoided. Baloxavir showed a small gain in QALYs versus laninamivir and the incremental cost per QALY gained (¥2,231,260) was lower than the considered willingness-to-pay threshold (¥5,000,000/QALY). Key model drivers were the probability of DRAEs and the duration of symptoms. The probability of baloxavir being cost-effective was 64%.
CONCLUSION: This cost-effectiveness study on baloxavir suggests that it would be cost-effective compared to laninamivir in OwH adults in Japan. Further studies are needed in different settings such as high-risk population and with different comparators.

PMID: 33243614 [PubMed - as supplied by publisher]

Adverse effects of interactions between antipsychotics and medications used in the treatment of cardiovascular disorders.

Pharmacol Rep. 2020 Apr;72(2):350-359

Authors: Siwek M, Woroń J, Gorostowicz A, Wordliczek J

Abstract
BACKGROUND: High level of comorbidity between bipolar disorder or schizophrenia and cardiovascular diseases (CVD) in clinical practice may contribute to drug-drug interactions between medications used in these conditions. The aim of this study was to evaluate harmful interactions between antipsychotics and medications used in treatment of CVD.
METHODS: The analysis of 52 cases of adverse reactions with a clinical picture indicates that they were the result of the combination of antipsychotic with cardiovascular medications.
RESULTS: The highest number of interactions with antipsychotics was recorded among beta-blockers (n = 13, 25% of all cases), including cardiac arrhythmias [atrial fibrillation (n = 1): risperidone plus atenolol; bradycardia (n = 1): perphenazine with metoprolol; ventricular arrhythmias: sertindole with metoprolol (n = 1) and ziprasidone with sotalol (n = 3)] and hypotension [chlorprotixene with nebivolol or metoprolol (n = 2)]. 12 cases concerned statins-myalgia, myopathy, or creatine kinase elevation appeared after combination of atorvastatin with haloperidol (n = 1), quetiapine (n = 3) or risperidone (n = 1), and simvastatin with quetiapine (n = 5) or risperidone (n = 2). There were also cases of interactions observed for the use of antipsychotics with anti-arrhythmic drugs (amiodarone, flecainide, propafenone) (n = 11), calcium channel blockers (n = 6), and other cardiac medications: clonidine, dabigatran, doxazosin, ivabradine, and losartan (n = 10).
CONCLUSIONS: Due to a high risk of interactions and related adverse effects, particular attention should be paid while using cardiovascular medications with antipsychotics. Clinical decisions should be preceded by a detailed analysis of safety, risk-benefit ratio to search for, as safe as possible, drug combinations.

PMID: 32124390 [PubMed - indexed for MEDLINE]

Oral nutritional supplement prevents weight loss and reduces side effects in patients in advanced lung cancer chemotherapy.

Amino Acids. 2020 Mar;52(3):445-451

Authors: Torricelli P, Antonelli F, Ferorelli P, Borromeo I, Shevchenko A, Lenzi S, De Martino A

Abstract
Weight loss in patients with cancer is caused by cancer cachexia and chemotherapy-induced nausea and vomiting. Recent developments in antiemetic drugs have substantially improved nausea and vomiting, but this intervention did not reduce weight loss and other more severe side effects of chemotherapy, like anorexia, weakness, cough, dyspnea, hemoptysis, and pain. This study aimed to investigate the effects of nutrition intervention with a food supplement, during chemotherapy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). Patients received individualized nutrition counseling by a registered dietitian and were provided with oral supplements of Texidrofolico® for 90 days. Bodyweight and the mentioned other side effects were evaluated at baseline and after 90 days of intervention. To assess the effects of this dietary supplement, a total of 30 patients were retrospectively enrolled as controls, and the bodyweight and change in side effects of chemotherapy were compared with those observed in 30 Texidrofolico®-treated patients. After 90-day intervention, by oral supplement of Texidrofolico®, the patients, during the course of cytotoxic chemotherapy, showed an improved quality of life and not significant weight and BMI loss respect the control group. Furthermore, the number of patients, treated with Texidrofolico® who maintained or increased their body weight, after 90 days of treatment was significantly higher than in the control group. The effects of treatment with the food supplement have also been studied from a metabolic point of view. It was possible to find that one of the known markers of tumor growth, plasma polyamines, was reduced after the treatment. A possible relationship between these biogenic amines and the folate cycle is discussed. In conclusion, early intensive nutrition intervention with oral supplements of Texidrofolico® during chemotherapy of NSCLC patients prevents weight loss and it is beneficial for their quality of life.

PMID: 32034492 [PubMed - indexed for MEDLINE]