Nevin Manimala

Cancer. 2022 Nov 21. doi: 10.1002/cncr.34507. Online ahead of print.

ABSTRACT

BACKGROUND: Antibody-drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their toxicity when applied in medical practice is of high importance.

METHODS: In a systematic review and meta-analysis of data gathered from different scientific databases (PubMed, Embase, Cochrane, and Web of Science) between January 1, 2000, and June 7, 2022, the authors applied a random-effects model with logit transformation and evaluated the heterogeneity between studies using I² statistics. The primary outcome was the incidence and 95% confidence interval (CI) for all-grade and grade ≥3 treatment-related adverse events and differences between different drugs, molecular structures, and cancer types.

RESULTS: In total, 2511 records were identified that included 169 clinical trials involving 22,492 patients. The overall incidence of treatment-related adverse events was 91.2% (95% CI, 90.7%-91.7%; I² = 95.9%) for all-grade adverse events and 46.1% (95% CI, 45.2%-47.0%; I² = 96.3%) for grade ≥3 adverse events. The most common all-grade adverse events were lymphopenia (53.0%; 95% CI, 48.7%-57.3%), nausea (44.1%; 95% CI, 43.2%-44.9%), neutropenia (43.7%; 95% CI, 42.6%-44.9%), blurred vision (40.5%; 95% CI, 37.4%-43.6%), and peripheral neuropathy (39.6%; 95% CI, 38.2%-41.1%); and the most common grade ≥3 adverse events were neutropenia (31.2%; 95% CI, 30.2%-32.3%), hypoesthesia (23.3%; 95% CI, 10.6%-35.9%), thrombocytopenia (22.6%; 95% CI, 21.3%-23.9%), febrile neutropenia (21.2%; 95% CI, 19.3%-23.1%), and lymphopenia (21.0%; 95% CI, 18.2%-23.7%).

CONCLUSIONS: Different ADCs appear to affect various treatment-related adverse events and provide comprehensive data on treatment-related adverse events for ADCs. The current results provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.

LAY SUMMARY: Unique anticancer drugs called antibody-drug conjugates (ADCs) have made significant progress in oncology in recent years because of their great success, and they are rapidly being used in the clinic as well as in hundreds of ongoing trials exploring their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment-related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.

PMID:36408673 | DOI:10.1002/cncr.34507

Colorectal Dis. 2022 Nov 21. doi: 10.1111/codi.16424. Online ahead of print.

ABSTRACT

INTRODUCTION: Empty pelvis syndrome is a source of considerable morbidity following a total pelvic exenteration. None of the available methods have been universally successful in mitigating this problem. We aimed to evaluate the safety and efficacy of the obstetric Bakri balloon in preventing empty pelvis syndrome.

METHODS: Combined prospective and retrospective study of all total pelvic exenterations for rectal cancers from a single institution was performed between October 2013 to May 2022. Bakri balloon was used since December 2019 in all patients that provided consent. Empty pelvis syndrome within 90 days was the primary end point, and included bowel obstruction, pelvic collection, and entero-perineal fistula. Comparison with the patients that did not have a Bakri balloon was performed.

RESULTS: Seventy-five patients with Bakri balloon were compared with 96 patients without the balloon placed after pelvic exenterations. No patient experienced an untoward complication from balloon deployment. The incidence of empty pelvis syndrome was 13.3% and 22.9% in the Bakri and no Bakri cohort, respectively (p-0.110). Every component of empty pelvis syndrome was proportionally lower without statistical significance. The number needed to treat to prevent EPS using the Bakri balloon was ten based on point estimates.

CONCLUSIONS: The use of Bakri balloon was safe without serious adverse events. The incidence of EPS after TPE was not statistically different with the use of Bakri Balloon despite a 9.6% reduction. A larger comparative study is needed to evaluate the efficacy of the balloon.

PMID:36408669 | DOI:10.1111/codi.16424

Angiology. 2022 Nov 19:33197221139915. doi: 10.1177/00033197221139915. Online ahead of print.

ABSTRACT

The Zwolle risk score was designed to stratify in-hospital mortality risk of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (pPCI) and for decision-making in the unit where patients are admitted. We assessed the accuracy of Zwolle risk score for in-hospital mortality estimation compared with the GRACE score in all patients (n = 4446) admitted for STEMI in 3 university hospitals. Only one fourth of the patients were classified as high-risk by the Zwolle risk score vs 60% by the GRACE score. In-hospital mortality was 10.6%. A statistically significant increase in in-hospital mortality, adjusted by age, gender, and revascularization, was observed with both scores. The assessment of the optimal cut-off points verified the accuracy of Zwolle score ≥4 as optimal threshold for high-risk categorization. In contrast, GRACE score ≥140 had very low specificity as well as percentage of patients correctly classified; GRACE score ≥175 was fairly better. The reclassification index of the Zwolle score after applying the GRACE score was 35.5%. Selection of high-risk STEMI patients treated with pPCI based on the Zwolle risk score has higher specificity than the GRACE score and might be useful in clinical practice.

PMID:36408662 | DOI:10.1177/00033197221139915

J Sch Nurs. 2022 Nov 20:10598405221132207. doi: 10.1177/10598405221132207. Online ahead of print.

ABSTRACT

This study aims to demonstrate the effect of a transtheoretical model (TTM)-based physical activity program on the exercise behavior of adolescents using WhatsApp. The study was conducted with high school students (N = 185) in a pre-/posttest, quasi-experimental design. TTM-based text messages were sent to the intervention group (n = 95) over WhatsApp every day for 8 weeks. The intervention group demonstrated more statistically significant progression in the exercising stages of change compared to the control group (n = 90) (χ² = 20.10; p = .00). It was also found that this group had a higher exercising self-efficacy score (t = 2.647; p = .009) and a higher physical activity total metabolic equivalent of task score (Z = -3.521; p = .000). There was no significant difference in BMI and perception of pros and cons (p > .05). The program was found to be effective in terms of recording progress in the exercising stages of change, increasing exercising self-efficacy, and maintaining a physical activity program.

PMID:36408658 | DOI:10.1177/10598405221132207

Ophthalmic Physiol Opt. 2022 Nov 21. doi: 10.1111/opo.13067. Online ahead of print.

ABSTRACT

PURPOSE: To study the effect of different soft contact lens (CL) materials during short-term wear on corneal tissue.

METHODS: Twenty-two healthy participants wore both silicone hydrogel (MyDay, CooperVision) and hydrogel soft CLs (Biomedics 1 day extra, CooperVision) for 8 h per lens. In each session, Scheimpflug images were captured before and immediately after CL removal. Images were analysed using the densitometry distribution analysis, a technique from which two parameters, α (corneal transparency) and β (corneal homogeneity), were estimated. In addition, the central corneal thickness changes after CL wear and the influence of the CL material on corneal transparency were evaluated.

RESULTS: The β parameter (homogeneity) increased by 5% after wearing both CL materials (paired t-test, p < 0.001). However, the α parameter (transparency) only increased in half of the participants. No material was found to be more determinant in causing the corneal densitometry changes. Statistically significant but not clinically relevant changes in corneal thickness were observed.

CONCLUSIONS: Biomarkers of corneal tissue integrity (α and β) were affected by short-term soft contact lens wear. The observed changes in corneal transparency and homogeneity were not clinically relevant but support the importance of participant-material biocompatibility.

PMID:36408647 | DOI:10.1111/opo.13067

Int J Stroke. 2022 Dec;17(10):1107-1113. doi: 10.1177/17474930211065640. Epub 2022 Jan 4.

ABSTRACT

BACKGROUND: Intracranial aneurysm (IA) is a crucial health concern with limited strategies for prevention and treatment.

AIM: To identify potentially modifiable risk factors, such as socioeconomic, behaviors, dietary, and cardiometabolic factors, for IA and its subtypes.

METHODS: Summary statistics for IA were derived from a genome-wide association study with an overall 79,429 participants. Single nucleotide polymorphisms associated with modifiable risk factors at genome-wide significance (P = 5 × 10^-8) were used as instrumental variables. The inverse-variance-weighted method, weighted-median method, Mendelian randomization (MR)-Egger regression, MR-Pleiotropy RESidual Sum and Outlier, and multivariable MR analyses were performed to evaluate the effect estimates.

RESULTS: Genetically predicted educational attainment, insomnia, smoking, and systolic and diastolic blood pressure (SBP and DBP) were significantly associated with the risk of IA. The odds ratios (ORs) were 0.44 (95% confidence interval (CI): 0.37-0.52) for educational attainment, 1.15 (95% CI: 1.08-1.23) for insomnia, 1.56 (95% CI: 1.38-1.75) for smoking initiation, 2.69 (95% CI: 1.77-4.07) for cigarette per day, 2.65 (95% CI: 1.72-4.08) for lifetime smoking, 1.07 (95% CI: 1.06-1.09), and 1.06 (95% CI: 1.04-1.10) for SBP and DBP, respectively. Similar effect estimates were observed for unruptured IAs and aneurysmal subarachnoid hemorrhage.

CONCLUSIONS: This study provided genetic evidence that several modifiable risk factors, including blood pressure, smoking, educational attainment, and insomnia were associated with the risk of IA.

PMID:36408635 | DOI:10.1177/17474930211065640

Eur J Hybrid Imaging. 2022 Nov 21;6(1):26. doi: 10.1186/s41824-022-00145-2.

ABSTRACT

BACKGROUND: Recent neuroimaging studies have demonstrated pathological mechanisms related to cerebral neuroplasticity in chronic low back pain (CLBP). Few studies have compared cerebral changes between patients with and without pain in the absence of an experimentally induced stimulus. We investigated the neurobiological substrates associated with chronic low back pain using [^99mTc]Tc-ECD brain SPECT and correlated rCBF findings with the numeric rating scale (NRS) of pain and douleur neuropathique en 4 questions (DN4). Ten healthy control volunteers and fourteen patients with neuropathic CLBP due to lumbar disc herniation underwent cerebral SPECT scans. A quantitative comparison of rCBF findings between patients and controls was made using the Statistical Parametric Mapping (SPM), revealing clusters of voxels with a significant increase or decrease in rCBF. The intensity of CLBP was assessed by NRS and by DN4.

RESULTS: The results demonstrated an rCBF increase in clusters A (occipital and posterior cingulate cortex) and B (right frontal) and a decrease in cluster C (superior parietal lobe and middle cingulate cortex). NRS scores were inversely and moderately correlated with the intensity of rCBF increase in cluster B, but not to rCBF changes in clusters A and C. DN4 scores did not correlate with rCBF changes in all three clusters.

CONCLUSIONS: This study will be important for future therapeutic studies that aim to validate the association of rCBF findings with the pharmacokinetic and pharmacodynamic profiles of therapeutic challenges in pain.

PMID:36404393 | DOI:10.1186/s41824-022-00145-2

Diabet Med. 2022 Nov 20:e15008. doi: 10.1111/dme.15008. Online ahead of print.

ABSTRACT

AIMS: To examine health behaviours and risk factors in women with pre-existing diabetes or previous gestational diabetes mellitus who are planning pregnancy.

METHODS: Health behaviour, risk factor and demographic data obtained from a digital pregnancy planning advisory tool (Tommy’s charity UK) were analysed. Descriptive statistical analysis was performed, stratified by diabetes type.

RESULTS: Data from 84,359 women, including 668 with type 1 diabetes, 707 with type 2 diabetes, and 1,785 with previous gestational diabetes obtained over a 12-month period (September 2019-September 2020) were analysed. 65%, 95%CI (61,68%) of women with type 2 diabetes and 46%, 95%CI (43,48%) with previous gestational diabetes were obese (BMI ≥30kg/m² ), compared with 26%, 95%CI (26,26%) without diabetes. Use of folic acid supplements was low; 41%, 95%CI (40,41%) of women without diabetes and 42%, 95%CI (40,45%) with previous gestational diabetes reported taking folic acid (any dose) while 47%, 95%CI (43,50%) women with type 1 diabetes and 44%, 95%CI (40,47%) women with type 2 diabetes respectively reported taking the recommended dose (5mg). More women with type 1 diabetes and type 2 diabetes reported smoking (20%, 95%CI (17,23%) and 23%, 95%CI (20,26%) respectively) and taking illicit/recreational drugs (7%, 95%CI (6,10%) and 9%, 95% CI (7,11%)) compared to women without diabetes (smoking 17%, 95% CI (16,17%), drug use 5%, 95%CI (5,5%)). Alcohol consumption, low levels of physical activity and of fruit and vegetable intake were also evident.

CONCLUSIONS: This study highlights the potential of online pregnancy planning advisory tools to reach high-risk women and emphasises the need to improve pre-pregnancy care for women with pre-existing diabetes and previous gestational diabetes, many of whom are actively seeking advice. It is also the first to describe pre-pregnancy health behaviours in women with previous gestational diabetes.

PMID:36404391 | DOI:10.1111/dme.15008

Animal Model Exp Med. 2022 Nov 20. doi: 10.1002/ame2.12291. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) is a polygenic metabolic disease, characterized by high fasting blood glucose (FBG). The ability of cranberry (CRN) fruit to regulate glycemia in T2D patients is well known. Here, a cohort of 13 lines of the genetically diverse Collaborative Cross (CC) mouse model was assessed for the effect of non-dialyzable material (NDM) of cranberry extract in lowering fasting blood glucose.

METHODS: Eight-week-old mice were maintained on either a standard chow diet (control group) or a high-fat diet (HFD) for 12 weeks, followed by injections of intraperitoneal (IP) NDM (50 mg/kg) per mouse, three times a week for the next 6 weeks. Absolute FBG (mg/dl) was measured bi-weekly and percentage changes in FBG (%FBG) between weeks 0 and 12 were calculated.

RESULTS: Statistical analysis showed a significant decrease in FBG between weeks 0 and 12 in male and female mice maintained on CHD. However, a non-significant increase in FBG values was observed in male and female mice maintained on HFD during the same period. Following administration of NDM during the following 6 weeks, the results show a variation in significant levels of FBG lowering between lines, male and female mice and under the different diets.

CONCLUSION: The results suggest that the efficacy of NDM treatment in lowering FGB depends on host genetic background (pharmacogenetics), sex of the mouse (pharmacosex), and diet (pharmacodiet). All these results support the need for follow-up research to better understand and implement a personalized medicine approach/utilization of NDM for reducing FBG.

PMID:36404387 | DOI:10.1002/ame2.12291

Drugs Aging. 2022 Nov 21. doi: 10.1007/s40266-022-00987-2. Online ahead of print.

ABSTRACT

BACKGROUND: Foundational therapies in heart failure improve clinical outcomes in heart failure with a reduced ejection fraction (HFrEF). Underuse of these life-prolonging heart failure therapies, such as sacubitril-valsartan, is common in older adults and has been associated with worse clinical outcomes. Characterizing the early benefits seen with these therapies might help increase their uptake in older adults.

OBJECTIVE: We applied several methods to estimate the time to benefit of an HFrEF therapy, using sacubitril-valsartan as a case study.

METHODS: PARADIGM-HF was a randomized controlled study on sacubitril-valsartan versus enalapril in stable, ambulatory HFrEF patients (n = 8399). The primary endpoint, a composite of death from cardiovascular causes or a first hospitalization for heart failure, was significantly reduced (sacubitril-valsartan (21.8%) versus enalapril (26.5%), hazard ratio (HR) 0.80 (95% confidence interval [CI] 0.73-0.87). We extracted and tabulated the Kaplan-Meier (KM) curves of the primary endpoint. An individual patient dataset was then reconstructed. The following methods were applied to explore the time to benefit of sacubitril-valsartan versus enalapril: visual estimation of the point of divergence of the KM curves, statistical process control (SPC), unadjusted landmark analyses using Cox proportional hazards analysis with 30-day increments until significance was persistently achieved, and comparing the survival probabilities of the extracted life tables.

RESULTS: Six raters visually estimated the time to benefit at a median of 60 days (interquartile range 38-10 days). Using SPC we found an early benefit from 28 days on, using the longest predefined control period of 28 days. An absolute risk reduction of 1 and 2% was found after 59 and 250 days, respectively. The reconstructed dataset provided a similar HR of 0.8004 (95% CI 0.7331-0.8739). Landmark analyses persistently showed statistical significance from 390 days and later. Survival probabilities differed from 35 days onward.

CONCLUSION: Using multiple approaches, the earliest benefit of sacubitril-valsartan compared to enalapril in stable HFrEF was found at about 1 month after initiation.

PMID:36404386 | DOI:10.1007/s40266-022-00987-2