Common Side Effects Research Articles

Flat dose intravenous immunoglobulin (IVIG) for primary infection prophylaxis after CAR-T for B-cell non-Hodgkin lymphoma (B-NHL).

e19004 Background: Prolonged hypogammaglobulinemia is a common side effect of CD19 chimeric antigen receptor (CAR) T-cell therapy for B-NHL. Average infection rates 1 year (yr) post CAR-T are 44-53% (Kampouri, Tran Infect Dis 2023). Prophylactic IVIG is typically dosed by weight; however, optimal dosing strategy remains unknown. We explored the efficacy of reduced flat IVIG dose on infection rates and non-relapse mortality (NRM) post CAR-T. Methods: B-NHL pts who received commercial CD19 CAR-T therapy from Nov 2017 to Mar 2023 at Vanderbilt Medical Center were included. All pts were on trimethoprim-sulfamethoxazole and valacyclovir for prophylaxis. IVIG at a flat dose of 10 grams was given for IgG < 400 mg/dL. Relevant clinical variables were collected from day 30 to 1 yr. Infections were defined as mild (treated outpatient), moderate (required admission), or severe (required intensive care unit) and by CTCAE v5 criteria. Severe neutropenia was defined as ANC<500 and severe lymphopenia was ALC<500. NRM was defined by death without progression or relapse. Estimated cost of therapy was $140/gram of IVIG based on previously published data. Results: A total of 43 pts (35 large cell lymphoma, 7 mantle cell lymphoma, and 1 follicular lymphoma) with median follow up of 445 days (range 134-2141) were included. Axicabtagene ciloleucel was given to 34 pts (79%), tisagenlecleucel to 2 pts (5%), and brexucabtagene autoleucel to 7 pts (16%). Median age was 58 (range 22-81). Median number of pre CAR-T therapies was 3 (range 1-7). There were 52 total infections with median time to first infection of 165 days (range 31-365). Of all infections, 21 (40%) were viral, 29 (56%) bacterial, and 2 (4%) fungal. There were 31 (60%) mild infections, 19 (36%) moderate, and 2 (4%) severe. Multiple G≥3 infections occurred in 14 pts (33%). At first infection, 4 pts (10%) had severeneutropenia and 13 pts (31%) had severelymphopenia. IVIG was given to 27 pts (63%). Median IgG at D30 was 438 mg/dL (range 143–1099) and 414 mg/dL (range 133–842) at D60. Prolonged IgG≤400 at 6 months occurred in 15 pts (35%). Median IVIG cost using flat dosing was $2800 (range $0-12,600) compared to a median cost of $8,075 (range $0-76,642) if weight-based dosing was utilized. NRM was 9% (4 pts). Of those pts, only 1 had a G≥3 infection during the first-year post CAR-T. Conclusions: We demonstrate comparable infection rates 1 yr post CD19 CAR-T and low NRM with the use of 10g flat IVIG dosing for consecutively treated pts. In addition, only 1 of 4 pts with NRM had severe infection within 1 yr. Notably, 35% of pts had persistent hypogammaglobulinemia at 6 mo and use of a flat dosing schedule provided substantial cost reduction. These findings should be validated in a prospective randomized trial.

The use of complementary and alternative medicine (CAM) among patients with cancer in Hawaii.

e24070 Background: Complementary and alternative medicine (CAM) involves medical products and practices that are not part of standard medical care. Various studies demonstrate potential benefits of CAM in alleviating certain side effects associated with cancer and cancer treatments. Our project aims to elucidate the prevalence, pattern of use, and proposed benefits of CAM among Hawaii residents with cancer. Methods: Our questionnaire based study recruited cancer patients from several outpatient oncology clinics across Oahu (n = 126). Patients were asked about CAM use and associated symptom benefit. Sociodemographic information was collected along with details about cancer type, treatment, and associated side effects. Participation was anonymous and optional. Results: At least one CAM therapy was used by 72/126 (57.1%) patients, while 54 (42.9%) did not use any CAM therapy. Among the CAM therapies, meditation and herbal supplements were most commonly used 26 (36.6%), followed by massage 25 (32.4%), and yoga 18 (25.4%). Stress reduction was the most common symptom benefit identified for various CAM therapies including meditation 13 (50%), herbal supplement 13 (50%), massage 13 (52%), and yoga 14 (77.8%). Anxiety reduction was another symptom benefit reported for meditation 13 (50%). Massage 13 (52%), CBD 14 (82.4%), and acupuncture 9 (64.3%) were also used for pain reduction. THC 12 (75%) and CBD 14 (82.4%) were used for sleep. Among the CAM users (n = 72), 52 (72.2%) did not speak to their clinician about CAM. We found that 107 (84.9%) patients experienced at least one side effect. The most common side effects experienced by patients were fatigue 81 (64.3%), hair loss 61 (48.4%), and constipation and/or diarrhea 57 (45.2%). The most commonly reported demographic information were the following: 95 (75.4%) female, 57 (45.2%) Asian, 33 (26.2%) 60-69 years old, 80 (63.5%) with breast cancer, and 33 (26.2%) with stage 4. Conclusions: We discovered that stress reduction is a symptom benefit associated with the most commonly used CAM therapies by cancer patients in Hawaii. Other symptom benefits involve anxiety, pain, and sleep. The modalities utilized were similar to nonpharmacologic therapies recommended by the NCCN guidelines for cancer survivorship, with the exception of herbal supplements. There is a lack of physician discussion regarding CAM use, which could impact the cancer burden in Hawaii. [Table: see text]

A phase II, multicenter, open-label study of polyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301).

3594 Background: The efficacy of checkpoint inhibitor immunotherapy in MSI-H mCRC has not been replicated in MSS mCRC. Therefore, additional interventions are needed to convert immunologically “cold” MSS CRC to “hot” tumors resembling MSI-H tumors. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine containing 12 immunogenic epitopes derived from 7 shared tumor antigens which demonstrated early evidence of clinical activity in first-line MSS mCRC. Methods: Patients with MSS mCRC who have progressed on 2-3 lines of prior chemotherapy regimen received PolyPEPI1018 (1.2 mg, sc) and atezolizumab (1,200 mg, iv) Q3W until disease progression or unacceptable toxicity. The primary endpoint was safety. A Simon 2-stage design was applied. Data on objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and correlation studies will be presented. Results: 18 patients (66 % female) were enrolled for stage 1 of the study. Median age was 54 years (range 38–79), 50% had liver metastases and 67% received at least 3 lines of prior therapies. PD-L1 expression was <1% for 85% of patients. The combination was well-tolerated; most common side effect related to treatment was Grade (Gr) 1-2 local skin reaction (n=22). Gr 2 events (n=2) at least possibly related to treatment were nausea, pyrexia and increased blood alkaline phosphatase. There were no Gr 3-5 events or study discontinuation due to treatment AE. The ORR was 0% and the DCR was 61%. The mPFS was 2.7 months (95%CI 1.4-4.0) and the mOS was not reached (95%CI 8.75 – NE months) at the data cut-off date. Ex-vivo FluoroSpot identified 13/16 subjects with robust, vaccine-specific CD8+ and/or CD4+ T cell responses detected against multiple vaccine antigens. For patients with available biopsy pairs (n=8), both the average PD-L1 expression (IC%, p=0.029) and the density of CD8+ tumor-infiltrating lymphocytes (TILs, p=0.019) were significantly increased, post-treatment. Patients with increased PFS (> 12 weeks) had both higher levels of post-treatment PD-L1 (p=0.007) and TILs (p=0.016) than patients with PFS ≤ 12 weeks. Conclusions: PolyPEPI1018 in combination with atezolizumab was well-tolerated with no Grade 3 AEs observed. Despite no objective tumor responses could be detected, correlative data suggest contribution of PolyPEPI1018-induced immune responses to the modulation of tumor microenvironment and to improved disease control. The study did not proceed to stage 2; it is on-going for the collection of survival data. Clinical trial information: NCT05243862 .

Impact of late immune effector cell associated hematotoxicity (ICAHT) and prolonged neutropenia after CAR-T therapy on infection and survival outcomes.

7041 Background: Prolonged hematologic toxicity is a common side effect of chimeric antigen receptor T-cell (CART) therapy. The EHA/EBMT panel developed the late ICAHT grading which incorporates depth of neutropenia after Day 30. Recently, the early ICAHT grade (D 0-30) was associated with infection (infx) and survival outcomes. Here, we evaluate the impact of late ICAHT and neutropenia on survival and infx outcomes after CD19 CART. Methods: We included two cohorts of adult patients (pts) with large B cell lymphoma (LBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL) who received commercial CD19 CART. Late was graded based on depth of neutropenia after D30 (G1 ≤ 1.5; G2 ≤ 1.0; G3 ≤ 0.5; G4 ≤ 0.1 G/L) and pts were censored for relapse, progression, or loss of follow up. Infxs after D30 were graded per CTCAE as mild G ≤ 2 or severe G ≥ 3. Cohort 1 included pts from 8 US medical centers for survival outcomes. Only data for severe infx was collected from D30-D100 and longer term infx data was not available. Landmark survival analysis at D+100 was performed using the Kaplan-Meier method and multivariate cox proportional hazards. To assess long term late infx outcomes, cohort 2 included pts at Vanderbilt with granular cytopenia and infx data (D30-365). Results: Cohort 1 included 277 pts with LBCL of whom 143 received axi-cel, 61 tisa-cel, and 72 liso-cel with median follow up 395 days (range 30-1763). By D100, there were 111 (40%) without, 89 (41%) with mild to moderate (G1-G2), and 53 (19%) with severe (G3-G4) late ICAHT. There were 13 pts (6%) with severe infx which was not associated with severe ICAHT (p=0.68). In multivariate landmark survival analysis using previously published covariates, severe late ICAHT was not associated with PFS (HR 1.64, p=0.11) or OS (HR 1.54, p=0.17); however, D100 neutropenia (ANC ≤ 1000) was associated with inferior PFS (HR 2.00, p=0.002) and OS (HR 1.95, p=0.003). NRM was 11% and associated with D100 neutropenia (p=0.015) but not late ICAHT (p=0.15). Cohort 2 had 43 pts (35 LBCL, 7 MCL, 1 FL) with median follow up 483 days (range 233-2133). 34 pts received axi-cel, 2 tisa-cel, and 7 brexu-cel. By 1 yr, there were 10 (23%) without, 27 (63%) with mild to moderate, and 6 (14%) with severe late ICAHT. There were 52 infxs by 1 yr and 16 pts (37%) had no infx. Median time to first infx after D30 was 165 days (range 31-365). There were 31 (60%) mild and 21 (40%) severe infx. IVIG was used in 28 (65%) and G-CSF in 27 (62%). Only 1 pt with severe ICAHT had severe infx. Late ICAHT and neutropenia were not associated with severe infection in logistic regression. Conclusions: These data did not show an association between EHA/EBMT late ICAHT grading and infx after D30 or survival. A detailed reporting of T and B cell reconstitution data may provide clues to better predict late infx. Persistent neutropenia at D100 was associated with inferior PFS and OS which needs validation in future studies.

Baseline PSMA PET/CT as a predictive biomarker for toxicity and patient-reported outcomes in mCRPC patients undergoing 177Lu-PSMA radioligand therapy.

e17058 Background: The phase III VISION trial demonstrated that 177Lu-PSMA-617 (PSMA-RLT) prolonged overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Common side effects of PSMA-RLT include xerostomia, bone pain, and myelosuppression. The objective of this study is to evaluate the role of baseline PSMA PET/CT (bPET) in predicting hematologic toxicity and patient-reported outcomes in mCRPC patients undergoing PSMA-RLT. Methods: Patients treated with 177Lu-PSMA-617 in the Expanded Access Program at UCLA with available bPET, toxicity data, and patient-reported outcomes (BPI, FACT-P, and Xerostomia Questionnaire) were included in this retrospective analysis. TRAQinform IQ technology (AIQ Solutions-Madison, WI) was used to conduct region of interest (ROI)-based analyses at bPET. SUVmean, SUVmax, volume (cm3), and total lesion PSMA (TLP; SUVmean x volume) of the whole-body tumor burden, healthy bone, and the salivary glands were extracted. We evaluated the following associations: 1) Whole-body tumor parameters on bPET with time to worsening of FACT-P scores (defined as a decrease of >10 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 2) Healthy bone parameters on bPET with time to worsening of BPI Pain Severity and Pain Interference scores (defined as a 30% increase or at least 2 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 3) Salivary gland parameters on bPET with Xerostomia Questionnaire scores (Mixed-effect linear regression model). Results: 61 mCRPC patients were included. When evaluating associations between healthy bone SUVmean, SUVmax, and TLP with time to first occurrence of Grade 3 or 4 hematologic toxicity, baseline hemoglobin was associated with a longer time to first occurrence (HR = 0.61, p = 0.005; HR = 0.59, p = 0.002; HR = 0.62, p = 0.005 respectively). When evaluating associations between bPET and time to worsening of FACT-P scores, whole-body tumor SUVmean, SUVmax, and TLP were associated with a longer time to worsening (HR = 0.74, p = 0.033; HR = 0.82, p = 0.01; HR = 0.91, p = 0.028 respectively). When evaluating associations between salivary gland SUVmean, volume, SUVmax, and TLP with Xerostomia Questionnaire scores, the number of cycles was associated with higher scores (mean estimate: 0.63, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.63, p = 0.003 respectively). Conclusions: In this retrospective analysis of 61 mCRPC patients treated with PSMA-RLT, bPET parameters were generally not predictive of hematologic toxicity or patient-reported outcomes. Of note, whole-body tumor SUV was associated with a longer time to worsening of FACT-P scores. Validation in a larger, prospective cohort is warranted.

Effectiveness and Safety of Dexmedetomidine in Neonates With Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia.

The objective of this study was to evaluate and compare the effectiveness and safety of dexmedetomidine as monotherapy between neonates with mild hypoxic ischemic encephalopathy (HIE) and moderate to severe HIE treated with therapeutic hypothermia (TH). This retrospective study included neonates of gestational age ≥36 weeks with a diagnosis of HIE and undergoing TH between January 2014 and December 2021. Patients were included if they received at least 6 hours of continuous sedation with dexmedetomidine. Baseline characteristics, dose and duration of medication, adverse events, liver and kidney function tests, and hospital course were reviewed. Of the 97 neonates included, 46 had mild, 42 had moderate, and 9 had severe HIE. Dexmedetomidine was initiated at a median 5 hours of life, and the median infusion duration was 77 (46-87) hours. Fifty-two (53.6%) required at least 1 breakthrough opioid or sedative during the first 24 hours of dexmedetomidine infusion. Overall, 40 patients (41.2%) had at least 1 bradycardia episode with heart rate <80 beats/min and 14 patients (14.4%) had heart rate <70 beats/min. Hypotension was experienced by 7 patients (7.2%). Fifty-two patients (53.6%) were intubated in the delivery room and 33/52 (63.5%) were extubated on day of life 1 during dexmedetomidine infusion. Dexmedetomidine as monotherapy was effective and safe sedation for infants with HIE undergoing hypothermia. The most common side effect of dexmedetomidine was bradycardia. -Dexmedetomidine may be considered as first and single agent for neonates with HIE undergoing TH.

Hemoglobin Concentration as an Indicator of Skin Radiation Damage During Radiation Therapy Treatments

Acute radiation dermatitis (ARD) is the most common side effect reported by patients undergoing radiation therapy (RT). Currently, the assessment of the severity of the reaction is based on the visual assessment of the skin, which is a subjective method, depending on many factors. The main aim of this study was to investigate the usefulness of hyperspectral imaging (HSI) in the assessment of ARD and find physiological factors that could be correlated with ARD. In this clinical pilot trial, weekly acquisitions of hyperspectral camera images of irradiated skin were performed for 5 weeks of RT and at the posttreatment follow-up visit which took place 30 to 40 days after the last fraction of RT. At the same time, the severity of radiodermatitis was assessed based on the criteria of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). The content and concentration of chromophores in irradiated skin were quantitatively determined using a hyperspectral camera. The use of HSI supported by image analysis and processing methods allowed for the determination of the content and distribution of hemoglobin and melanin in the irradiated skin. It was found that the hemoglobin concentration is correlated with the subjective assessment made according to the CTCAE protocol. HSI is a sensitive and specific method of analyzing the concentration of chromophores in the skin, including hemoglobin. A clear correlation was found between hemoglobin concentration and CTCAE v.5 scale because of which HSI can be considered as an objective method of skin assessment during RT.

Oral administration of probiotic spore ghosts for efficient attenuation of radiation-induced intestinal injury

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients’ quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.

COVID-19 vaccination among adolescents and young adults with chronic kidney conditions: a single-center experience.

Following the pandemic of COVID-19, the main focus has been on COVID-19 vaccines and herd immunity. Although the safety of the COVID-19 vaccines has been shown in clinical trials, children with chronic diseases were not included. We investigated the side effect profile and safety of the COVID-19 vaccines in adolescents with kidney disease. A questionnaire including demographic information, history of COVID-19, vaccination status, and vaccine-related side effects was administered to the patients with chronic kidney disease (CKD) stage 2-5, glomerular disease treated with immunosuppression, and kidney transplant recipients. Ninety-eight patients were vaccinated with CoronaVac-inactivated SARS-CoV-2 (n=16) or BNT162b2 messenger RNA (mRNA) COVİD-19 (n=82) vaccine. The mean age was 16.90±2.36 years. The most common side effects were local pain, fatigue, and fever. No serious side effects or renal disease flare were observed. There was no significant difference in the side effects reported after the BNT162b2 mRNA-RNA as compared to the Corona Vac-inactivated SARS-CoV-2 vaccine. No significant relationship was found between the frequency of side effects according to age, glomerular filtration rate, immunosuppressive treatments, CKD stage, and the underlying disease. Although the reported data are subjective because they were obtained through a questionnaire and studies with long-term follow-up are needed, our early experience suggests that the vaccine is safe and adolescents and young adults should be encouraged to be vaccinated.

Prevalence of headaches in healthcare workers while using personal protective equipment during the COVID-19 pandemic: a systematic review and meta-analysis

ObjectivesDuring the COVID-19 pandemic, healthcare workers (HCWs) are at a serious risk of contracting this virus. Therefore, they should use personal protective equipment (PPE) to protect themselves. Long-term use of...

The somatotroph pituitary gland function in high-aged multimorbid hospitalized patients with IGF-I deficiency

PurposeIt is unclear whether the age-related decline in the somatotropic axis stems from a reduced growth hormone (GH) production in the pituitary gland, or from a peripheral origin akin to an acquired GH resistance. With the help of a GHRH/arginine test, high-aged multimorbid hospitalized patients with IGF-I deficiency are to be tested to determine whether there is primarily a pituitary GH deficiency in the sense of a somatopause.MethodsSeventeen multimorbid patients (eleven men and six women) with a mean age of 82 years, with IGF-I concentrations below two standard deviations of 30-year-old men and women were identified. Patients suffered from a variety of common age-related stable diseases including coronary artery disease, chronic liver or kidney disease, chronic heart failure as well as acute conditions e.g., urosepsis or endocarditis. To assess the somatotropic axis they underwent a GHRH/arginine test. Results were evaluated using descriptive statistics.ResultsIn average, the peak concentration of GH after stimulation was 14.8 µg/L with a range from 2.76 to 47.4 µg/L. Taking into account both, gender and BMI (with a mean of 26.5 kg/m²) for each participant, the pituitary gland was adequately stimulated in 16 out of the 17 patients. No patient reported common side effects related to the GHRH/arginine test.ConclusionThe somatotroph pituitary gland retains its secretory capacity in the advanced aged. Therefore, age does not seem to be the driving pacemaker for the functional decline of the somatotropic axis within the aged population.

Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid-induced myopathy.

Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time. This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors. This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit. The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM. GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered.

Risk factors of peri-intubation cardiovascular collapse in critically ill patients

Aim: Peri-intubation cardiovascular collapse is a common side effect of tracheal intubation and is associated with increased mortality in critically ill patients. We aimed to determine the potential risk factors associated with peri-intubation cardiovascular collapse. Methods: This is a prospective observational study of patients who were critically ill and undergoing tracheal intubation from August 1, 2022 to February 28, 2023. The primary outcome was peri-intubation cardiovascular collapse. Peri-intubation cardiovascular collapse was defined as systolic blood pressure

A Cross Sectional Survey of Factors Related to Cannabis Use as a Sleep Aid Among Canadian Cancer Survivors

ABSTRACT Objectives Poor sleep is a common side effect of cancer. Cannabis is increasingly used to manage cancer treatment-related symptoms, including sleep. This study investigated factors related to cannabis use for sleep among Canadian cancer survivors. Method Adult Canadian cancer survivors (N = 940) were recruited via the Angus Reid Institute and completed an online, cross-sectional survey. Univariate and multiple binomial logistic regression models identified factors associated with cannabis use for sleep. Results Of the participants (Mage = 64.5 yrs; Women = 51.1%; White = 92.9%), 25.1% (n = 236) currently use cannabis for sleep. Participants were at greater odds of using cannabis for sleep if they identified as a gender other than man or woman (AOR = 11.132), were diagnosed with multiple medical conditions (2:AOR = 1.988; 3+:AOR = 1.902), two psychological conditions (AOR = 2.171), multiple sleep disorders (AOR = 2.338), insomnia (AOR = 1.942), bone (AOR = 6.535), gastrointestinal (AOR = 4.307), genitourinary (AOR = 2.586), hematological (AOR = 4.739), or an unlisted cancer (AOR = 3.470), received hormone therapy only (AOR = 3.054), drink heavily (AOR = 2.748), or had mild insomnia (AOR = 1.828). Older participants (AOR=.972) and those with sleep apnea were less likely to use cannabis for sleep (AOR=.560). Conclusion Given its prevalence, research is needed to understand how factors associated with cannabis use as a sleep aid among Canadian cancer survivors may influence its use and effectiveness and whether these factors are barriers to accessing evidence-based treatments.

Modelling chemotherapy-induced cardiotoxicity with live myocardial slices: from bedside to bench and back again

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Netherlands Heart Institute &amp; Dutch Heart Foundation (Dekker Senior Clinical Scientist 2019) Introduction Cancer therapy related cardiac dysfunction (CTRCD) is a common side-effect of many oncological regimens. The prevention, diagnosis and treatment of CTRCD requires a well-orchestrated management by a multidisciplinary team composed by oncologists, cardiologists, radiologists, but less often translational scientists. Purpose In this work, we investigated the translational potential of live myocardial slices derived from a patient presenting with acute biventricular failure, with no history of cardiovascular disease, who had previously received neo-adjuvant chemotherapy containing doxorubicin (240 mg/m2) and trastuzumab, for the treatment of a breast carcinoma. In contrast to anthracycline cardiotoxicity, which is often permanent, cardiac dysfunction caused by trastuzumab is commonly reversible after cessation of treatment. Herein, we provide a novel side-by-side comparison of myocardial function ex vivo and clinical outcomes in the patient. Methods After several days on extracorporeal life support and inotropic therapy, the patient’s cardiac function did not improve. The patient was ultimately implanted with a left- and right-ventricular assist device (LVAD and RVAD, respectively). Live myocardial slices were produced from the apical biopsy obtained during LVAD implantation and cultured in a biomimetic system under physiological mechanical and electrical conditions. Slices were subsequently exposed to doxorubicin, trastuzumab or vehicle (0.1% DMSO) for a continued period of 7 days. Contractile force was recorded continuously, and a custom-made stimulation protocol applied every 24h. To evaluate responsiveness to inotropes, slices were incubated with milrinone before culture termination. Calcium transients and action potentials were determined optically using calcium and voltage-sensitive dyes. Results Continued exposure to either doxorubicin or trastuzumab limited the recovery of contractility in myocardial slices. In contrast, vehicle controls showed a robust recovery and development of stronger contractile forces. Doxorubicin-treated slices were less responsive to stimulation, displayed increased stimulation threshold and were less able to follow pacing at higher frequencies. Optical mapping revealed that exposure to doxorubicin led to the development of abnormal calcium handling. In parallel to the ex vivo findings, RVAD/LVAD-mediated cardiac unloading and the absence of any chemotherapy drug, resulted in a significant recovery of right-ventricular function, enabling RVAD removal within 2 weeks. Conclusions The complex nature of chemotherapy-induced cardiotoxicity imposes numerous challenges in clinical decision-making. In this unique case, patient care could be paralleled by concomitant state-of-the-art ex vivo tissue culture. We observed that myocardial tissue slices could partially recapitulate clinical observations, highlightings the promising synergy between translational science and personalized patient care.

A Comprehensive Review of the Research Literature on External Cephalic Version (ECV)

External cephalic version (ECV) is an approach to turning a fetus from the breech presentation by external maneuvering of the fetus through the maternal abdominal wall into a cephalic presentation. We conducted a systematic search of the current literature on ECV to provide a comprehensive overview of the procedure and associated success rates, risks, and alternatives to ECV. Tocolytics can improve ECV success, but none of the tocolytics shown to be effective for ECV are currently available in Canada. The factors that can best predict ECV success are low uterine tone (associated with parity or tocolytics), easy palpation of the fetal head, and an unengaged breech. The most common side effect of ECV is transient fetal bradycardia with an incidence of one to six percent of all ECV procedures. The risk of requiring an emergency caesarean section because of ECV appears to be around 0.5% or one in 200 ECV procedures performed. Our review suggested no significant risk of fetal/neonatal mortality or serious morbidity associated with ECV. Few alternative approaches to turning a fetus in the breech presentation have been adequately studied. ECV should be considered for all women with a fetus in the breech presentation at term in the absence of any contraindications to the procedure.

Efficacy and Safety of Bromocriptine-QR as an Adjunctive Therapy on Glycemic Control in Subjects with Uncontrolled Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

There has been an increasing awareness of the effects of combining bromocriptine-QR with other medications for diabetes mellitus type 2. This study aimed to assess the efficacy and safety of bromocriptine-QR as an adjunctive therapy for patients with uncontrolled type 2 diabetes mellitus. This systematic review is registered at the International Prospective Register of Systematic Reviews (CRD42022360326). Literature search was done via MEDLINE, NCBI, Google Scholar, Science Direct, Europe PMC and Cochrane Library databases. We included randomized controlled trials with participants 18 years old and above with uncontrolled type 2 diabetes mellitus. The primary outcome of interest is the efficacy and safety of bromocriptine-QR as an adjunctive therapy for glycemic control. Case reports, case series, reviews and animal studies were excluded. The risk of bias was reviewed using the Cochrane Risk of Bias tool. Meta-analysis was performed using Review Manager 5.4 and presented as a weighted mean difference and 95% confidence interval for changes from the baseline level. Nine studies were included in the systematic review with a total of 2709 participants. The baseline HbA1c in the bromocriptine-QR group was 7.42% and 7.51% in the control group. The bromocriptine-QR group was favoured, outperforming the control group in terms of reducing hemoglobin A1c(HbA1c), with a statistically significant difference (weighted mean difference -0.6%; 95% CI [-0.83,-0.36]; p<0.00001). The most common side effects were nausea (33.75% vs 6.92%), fatigue (13.11% vs 5.94%), and headache (11.17% vs 6.87%). Administration of bromocriptine-QR at a dose range of 1.6 to 4.8 mg/day as an adjunctive therapy reduced HbA1c and FBG in patients with uncontrolled type 2 diabetes mellitus (T2DM). However, there were also statistically greater odds of the occurrence of adverse events such as nausea, vomiting, and headache compared to controls.

YouTube and the implementation and discontinuation of the oral contraceptive pill: A mixed-method content analysis.

Women living in high-quality healthcare systems are more likely to use oral contraceptives at some point in their lives. Research findings have sparked controversial discussions about contraception in the scientific community and the media, potentially leading to higher rates of method discontinuation. Understanding the underlying motives for method discontinuation is crucial for reproductive health equity and future programming interventions. To address this question, this study aims to explore women's experiences of oral contraceptive use and discontinuation on YouTube. A concurrent explanatory mixed-methods design was used to conduct content analysis of German YouTube videos. The information from 175 videos of 158 individuals was extracted through quantitative descriptive content analysis. Twenty-one individuals were included in the qualitative content analysis. The body was a recurring theme in the pill biographies. Women described, for example, bodily sensations as reasons for taking and stopping the pill. They also described positive and negative side effects while taking the pill and after stopping. The most common side effects of taking the pill mentioned by YouTubers were mood swings (76/158), weight gain (45/158), headaches (33/158), and depressed mood (45/158). The symptoms after discontinuation reported most were facial skin impurities (108/158), decreased mood swings (47/158), hair loss (42/158), and weight loss (36/158). Overall, women overwhelmingly rated their discontinuation experience as positive (87/91). The study identified key symptoms of oral contraceptive initiation and discontinuation by portraying the experiences of female YouTubers, adding valuable insights to the understanding of method initiation and discontinuation. Further research is needed to explore women's personal experiences with method discontinuation beyond the YouTube platform.

A Possible Solution to Statin Noncompliance

Dear Sir/Madam Pakistan is one of the top six countries for Cardiovascular deaths and it is estimated that 4.7 million people will die from Cardiovascular deaths between 2005-2027[1]. Considering the burden of cardiovascular disease, it is imperative that we focus our efforts on preventing and addressing risk factors while simultaneously ensuring that the goals of our preventive strategies are met. One such issue arises with statins. Statin drugs are the first line drug therapy for dyslipidemia (a significant risk factor for CVDs) and the most widely prescribed drugs for dyslipidemia treatment as per both the American and European guidelines [2]. Statin drugs are essential for improving cardiovascular outcomes [2]. However, a challenge with statin therapy is nonadherence to the drug as shown by various studies. The percentage of patients taking statin dropped to 60.3% in one year and 48.8% in five years as shown by a cohort study on 1221 patients [3]. Statin associated muscle symptoms are the most common side effect implicated in patients discontinuing therapy. A meta-analysis showed that patients with statin-associated myopathy had significantly lower vitamin D levels than non-myopathy patients. This study pooled the results of four studies to show a significant increase in tolerance rate after vitamin D supplementation [4]. A randomized control trial showed a decrease in cardiorespiratory fitness with statin drugs, significantly reduced in the group of statins plus vitamin D supplementation [5]. These studies show the positive results of vitamin D supplementation when given with statin. It is, thus, possible for us to increase compliance with statin therapy and improve patients' exercise performance on statin drugs. Considering the impact of CVDs on our population and the pivotal part of Statin therapy, any related development can have a vast clinical impact and should be welcomed. We believe that general physicians should be made aware of such discoveries. Further, guidelines could be updated with inclusions of Vitamin D with high intensity Statin therapy. Finally, the importance of these drugs warrants further clinical trials to assess the feasibility of their use with vitamin D.

Healthcare professionals’ knowledge, understanding and confidence to manage chronic pain after cancer treatment: A UK survey

IntroductionHealthcare professionals are vital in preparing people living with and beyond cancer about the risks of chronic pain after cancer treatment. To do so, healthcare professionals need to be knowledgeable and confident about chronic pain after cancer treatment, yet little is known about their understanding or confidence of this common long-term and late side effect of cancer treatment. AimTo identify healthcare professionals’ knowledge and understanding of chronic pain after cancer treatment and consider how confident they are to inform, listen and signpost people living with and beyond cancer to appropriate information and support. MethodA cross sectional online survey was distributed to healthcare professionals in the UK via cancer and primary care networks, cancer alliances and social media. The survey consisted of four domains: 1) knowledge and understanding, 2) information and support, 3) confidence and 4) barriers. Quantitative data were analysed with descriptive statistics and free text comments were analysed using qualitative content analysis. ResultsHealthcare professionals reported limited knowledge and understanding of chronic pain after cancer treatment. Healthcare professionals lacked confidence to talk to people about chronic pain after cancer treatment and viewed their lack of knowledge as a barrier. Additional barriers included ‘Limited service provision’, ‘Conflict between services’, ‘Not my role’ and ‘Challenges in diagnosing chronic pain in cancer survivors’. ConclusionChronic pain after cancer can be a significant issue for those living with and beyond cancer, yet healthcare professionals report limited knowledge of it or understanding of the impact. More education is needed to increase healthcare professionals’ knowledge and confidence in chronic pain after cancer treatment.