Indian J Pharmacol. 2023 Mar-Apr;55(2):138-140. doi: 10.4103/ijp.ijp_811_21.

ABSTRACT

All-trans-retinoic acid (ATRA) has transformed the treatment of acute promyelocytic leukemia. Most of the adverse effects associated with this drug are minor barring differentiation syndromes. Genital ulcers feature among the underreported adverse effects of ATRA which needs to be kept in mind to avoid life-threatening complications. We describe two cases who developed genital ulcers while treated with ATRA.

PMID:37313940 | DOI:10.4103/ijp.ijp_811_21

J Cancer Res Ther. 2023 Jan-Mar;19(2):519. doi: 10.4103/jcrt.jcrt_1257_21.

NO ABSTRACT

PMID:37313930 | DOI:10.4103/jcrt.jcrt_1257_21

J Cancer Res Ther. 2023 Jan-Mar;19(2):241-252. doi: 10.4103/jcrt.jcrt_253_22.

ABSTRACT

BACKGROUND: Radical surgery for cervical cancer has inherent benefits, and as upfront or post neoadjuvant chemotherapy (NACT), is extendable to locally advanced cancer cervix (LACC), with postoperative radiotherapy (PORT) for high-risk factors. Objective of the study was to compare the effectiveness and survival between non-PORT and PORT in high-risk early stages.

MATERIALS AND METHODS: Radical hysterectomies conducted between January 2014 and December 2017 were evaluated and followed till December 2019. Clinical, surgical-pathologic characteristics, and oncological outcomes were compared between non-PORT and PORT groups. A similar comparison was made between alive and dead patients within each group. The impact of PORT was assessed.

RESULTS: Of 178 radical surgeries, early-LACC constituted 70%. Most (37%) of the patients belonged to stage 1b2, while stage 2b formed 5%. Mean age of patients was 46.5 years; 69% were below 50 years of age. Abnormal bleeding (41%) was the predominant symptom, followed by postcoital (20%) and postmenopausal bleeding (12%). Upfront surgeries formed 70.2%, and the average waiting period was 1.93 months (range: 1-10 months). PORT patients were 97 (54.5%) in number and the remaining formed the non-PORT group. Mean follow-up was 34 months, with 118 (66%) alive patients. Significant adverse prognostic factors were tumors >4 cm (44.4% patients), positive margins (10%), lymphatic vascular space invasion (LVSI; 42%), malignant nodes (33%), multiple metastatic nodes averaging seven (range: 3-11), and delayed (>6 months) presentation, but not deep stromal invasion (77% patients) and positive parametrium (8.4% patients). PORT overcame the adverse effects of tumors >4 cm, multiple metastatic nodes, positive margins, and LVSI. Total recurrences (25%) were balanced for both groups, but recurrences within 2 years were significantly more for PORT. Two-year overall survival (78%) and recurrence-free survival (72%), median overall survival (21 months), and median recurrence-free interval (19 months) were significantly better for PORT, with the complication rates being similar.

CONCLUSION: PORT had significantly better oncological outcomes compared to non-PORT. Multimodal management is worthwhile.

PMID:37313903 | DOI:10.4103/jcrt.jcrt_253_22

Zhonghua Er Ke Za Zhi. 2023 Jun 2;61(6):550-555. doi: 10.3760/cma.j.cn112140-20230417-00280.

ABSTRACT

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.

PMID:37312468 | DOI:10.3760/cma.j.cn112140-20230417-00280

Trials. 2023 Jun 13;24(1):400. doi: 10.1186/s13063-023-07284-2.

ABSTRACT

BACKGROUND: As cancer therapies increase in their complexity, effective communication among patients, physicians, and research staff is critical for optimal clinical trial management. Currently, we understand little about on-trial communication practices and patient trial experiences over time. This mixed-method study explored patient experiences of participating in a clinical drug trial at different time points, focussing on patient communication with trial staff.

METHODS: Patients enrolled in clinical drug trials conducted at the Parkville Cancer Clinical Trials Unit were invited to complete a tailored online survey and/or a qualitative interview. Patients were recruited to three cohorts based on time since the first trial treatment: new (≥ 1 to ≤ 13 weeks), mid- (≥ 14 to ≤ 26 weeks), and long-term (≥ 52 weeks) trial patients. Descriptive statistics were calculated for survey responses. Interview data were analysed thematically with a team-based approach. Survey and interview data were integrated at the intepretation stage.

RESULTS: From May to June 2021, 210 patients completed a survey (response rate 64%, 60% male), 20 completed interviews (60% male), and 18 completed both. More long-term trial patients (46%) participated than new (29%) and mid-trial patients (26%). Survey data showed high (> 90%) patient satisfaction with the provision of trial information and communication with trial staff across trial stages, and many reported trial experiences as above and beyond standard care. Interview data indicated that written trial information could be overwhelming, and verbal communication with the staff and physicians was highly valued, especially for enrolment and side effect management among long-term patients. Patients described the key points along the clinical trial trajectory that merit close attention: clear and well-communicated randomisation practices, reliable pathways for side effect reporting and prompt response from the trial staff, and end-of-trial transition management to avoid a sense of abandonment.

CONCLUSION: Patients reported high overall satisfaction with trial management but outlined key pinch points requiring improved communication practices. Establishing a range of effective communication practices among trial staff and physicians with patients in cancer clinical trials may have a wide range of positive effects on patient accrual, retention, and satisfaction.

PMID:37312206 | DOI:10.1186/s13063-023-07284-2

Sci Rep. 2023 Jun 13;13(1):9576. doi: 10.1038/s41598-023-36791-0.

ABSTRACT

Poor survival of seeds reduces the production efficiency of the sea cucumber Apostichopus japonicus in pond culture. We investigated the effects of sea mud on the movement-related behaviors of A. japonicus with different body sizes. Mud significantly decreased crawling behavior and wall-reaching behavior in small seeds (~ 1 g of body weight), but not in the large ones (~ 2.5 g of body weight). These behaviors were significantly greater in the large seeds of A. japonicus than those in the small individuals when they were both on the mud. This clearly suggests that mud has negative effects on the movement-related behaviors of small seeds, but not on large individuals. We further assessed the effects of inevitable transport stress on the movement-related behaviors of A. japonicus on mud. Significantly poorer performances in crawling behavior, wall-reaching behavior and struggling behavior were observed in stressed A. japonicus (both sizes) than those in unstressed groups. These new findings indicate that transport stress further increases the adverse effects on the movement-related behaviors of A. japonicus on mud. Moreover, we investigated whether adverse effects can be reduced when individuals are directly seeded onto artificial reefs. Crawling behavior, wall-reaching behavior and struggling behavior in stressed A. japonicus (both sizes) seeded onto artificial reefs were significantly greater than those on mud, whereas artificial reefs did not significantly improve the crawling and struggling behaviors of unstressed small seeds. These results collectively indicate that mud and transport stress show negative impacts on the movement-related behaviors of sea cucumbers. Artificial reefs greatly reduce these adverse effects and probably contribute to improving the production efficiency of sea cucumbers in pond culture.

PMID:37311947 | DOI:10.1038/s41598-023-36791-0

Nat Commun. 2023 Jun 13;14(1):3489. doi: 10.1038/s41467-023-39013-3.

ABSTRACT

Ulcerative colitis is a chronic inflammatory bowel disease that strongly affects patient quality of life. Side effects of current therapies necessitate new treatment strategies that maximise the drug concentration at the site of inflammation, while minimizing systemic exposure. Capitalizing on the biocompatible and biodegradable structure of lipid mesophases, we present a temperature-triggered in situ forming lipid gel for topical treatment of colitis. We show that the gel is versatile and can host and release drugs of different polarities, including tofacitinib and tacrolimus, in a sustained manner. Further, we demonstrate its adherence to the colonic wall for at least 6 h, thus preventing leakage and improving drug bioavailability. Importantly, we find that loading known colitis treatment drugs into the temperature-triggered gel improves animal health in two mouse models of acute colitis. Overall, our temperature-triggered gel may prove beneficial in ameliorating colitis and decreasing adverse effects associated with systemic application of immunosuppressive treatments.

PMID:37311749 | DOI:10.1038/s41467-023-39013-3

BMJ Open. 2023 Jun 13;13(6):e069047. doi: 10.1136/bmjopen-2022-069047.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of combination immunochemotherapy regimens for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

DESIGN: Meta-analysis and systematic review.

DATA SOURCES: PubMed, Embase, Web of Science and Cochrane library and the Clinicaltrials.gov clinical trials registry were searched up to 14 March 2022.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomised controlled trials that compared combination immunochemotherapy with conventional chemotherapy for R/M HNSCC. Primary outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse effects (AEs).

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data.

RESULTS: A total of 1214 relevant papers were obtained after the initial search, and five papers that met the inclusion criteria were included; these studies included a total of 1856 patients with R/M HNSCC. Meta-analysis showed that the OS and PFS of patients with R/M HNSCC in the combination immunochemotherapy group were significantly longer than those in the conventional chemotherapy group (HR=0.84; 95% CI 0.76, 0.94; p=0.002; HR=0.67; 95% CI 0.61, 0.75; p<0.0001), and the ORR was significantly higher (OR=1.90; 95% CI 1.54, 2.34; p<0.00001). The analysis of AEs showed that there was no significant difference in the overall incidence rate of AEs between two groups (OR=0.80; 95% CI 0.18, 3.58; p=0.77), but the rate of grade III and IV AEs was significantly higher in patients in the combination immunochemotherapy group (OR=1.39; 95% CI 1.12, 1.73; p=0.003).

CONCLUSIONS: Combination immunochemotherapy prolonged OS and PFS in patients with R/M HNSCC and improved the ORR; while this approach did not increase the overall incidence of AEs in patients, it increased the rate of grade III and IV AEs.

PROSPERO REGISTRATION NUMBER: CRD42022344166.

PMID:37311638 | DOI:10.1136/bmjopen-2022-069047

Monogr Soc Res Child Dev. 2023 Jun;88(1):7-182. doi: 10.1111/mono.12463.

ABSTRACT

We examine the North Carolina Pre-K (NC Pre-K) program to test the hypothesis that observed variation in effects resulting from exposure to the program can be attributed to interactions with other environmental factors that occur before, during, or after the pre-k year. We examine student outcomes in 5th grade and test interaction effects between NC's level of investment in public pre-k and moderating factors. Our main sample includes the population of children born in North Carolina between 1987 and 2005 who later attended a public school in that state, had valid achievement data in 5th grade, and could be matched by administrative record review (n = 1,207,576; 58% White non-Hispanic, 29% Black non-Hispanic, 7% Hispanic, 6% multiracial and Other race/ethnicity). Analyses were based on a natural experiment leveraging variation in county-level funding for NC Pre-K across NC counties during each of the years the state scaled up the program. Exposure to NC Pre-K funding was defined as the per-4-year-old-child state allocation of funds to a county in a year. Regression models included child-level and county-level covariates and county and year fixed effects. Estimates indicate that a child's exposure to higher NC Pre-K funding was positively associated with that child's academic achievement 6 years later. We found no effect on special education placement or grade retention. NC Pre-K funding effects on achievement were positive for all subgroups tested, and statistically significant for most. However, they were larger for children exposed to more disadvantaged environments either before or after the pre-k experience, consistent with a compensatory model where pre-k provides a buffer against the adverse effects of prior negative environmental experiences and protection against the effects of future adverse experiences. In addition, the effect of NC Pre-K funding on achievement remained positive across most environments, supporting an additive effects model. In contrast, few findings supported a dynamic complementarity model. Instrumental variables analyses incorporating a child's NC Pre-K enrollment status indicate that program attendance increased average 5th grade achievement by approximately 20% of a standard deviation, and impacts were largest for children who were Hispanic or whose mothers had less than a high school education. Implications for the future of pre-k scale-up and developmental theory are discussed.

PMID:37309210 | DOI:10.1111/mono.12463

Br J Clin Pharmacol. 2023 Jun 13. doi: 10.1111/bcp.15824. Online ahead of print.

ABSTRACT

AIM: Misoprostol is a prostaglandin E1 analog that is used to prevent non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal disorders. The aim of this systematic review and meta-analysis was to evaluate whether use of misoprostol also decreases the risk of NSAID-induced kidney injury.

METHODS: Randomized controlled trials that compared misoprostol versus placebo in an adult patient population were selected. The primary outcome was kidney injury and the secondary outcome was severe adverse events. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

RESULTS: Twelve studies were eligible for inclusion. Although the rates of kidney injury and severe adverse events did not differ significantly between misoprostol and placebo, a post-hoc sub-group analysis that excluded studies in which different NSAIDs were used in the misoprostol and placebo groups suggested that misoprostol may reduce the risk of NSAID-induced kidney injury (risk difference -0.09, 95% confidence interval -0.15 to -0.03, P<0.01, I2 = 87%; evidence of very low certainty).

CONCLUSIONS: There is limited evidence that misoprostol reduces the risk of NSAID-induced kidney injury. Misoprostol possibly contributes to reducing the risk of kidney injury associated with chronic NSAID use. The findings of this meta-analysis suggest further high-quality clinical trials are warranted.

PMID:37309574 | DOI:10.1111/bcp.15824

J Blood Med. 2023 Jun 7;14:379-388. doi: 10.2147/JBM.S405624. eCollection 2023.

ABSTRACT

INTRODUCTION: Previous clinical trials established the efficacy and safety of sucrose-formulated recombinant factor (F) VIII (rFVIII-FS/Kogenate FS®/Helixate FS®) and octocog alfa (BAY 81-8973/Kovaltry®; LEOPOLD trials).

AIM: To report the results of a post hoc subgroup analysis assessing efficacy and safety outcomes in patients with hemophilia A who were receiving rFVIII-FS prior to enrolling into the LEOPOLD I Part B and LEOPOLD Kids Part A clinical trials and switching to octocog alfa.

METHODS: LEOPOLD I Part B (NCT01029340) and LEOPOLD Kids Part A (NCT01311648) were octocog alfa Phase 3, multinational, open-label studies in patients with severe hemophilia A aged 12-65 years and ≤12 years, respectively. Annualized bleeding rate (ABR) was the efficacy endpoint for both studies. Safety endpoints included adverse events (AEs) and development of FVIII inhibitors.

RESULTS: Of the 113 patients in both LEOPOLD trials, 40 (35.4%) patients received rFVIII-FS prophylaxis pre-study and had data available for pre-study total ABR. In LEOPOLD I Part B (n = 22, 35.5%), median (Q1; Q3) total ABR decreased from 2.5 (0.0; 9.0) pre-study to 1.0 (0.0; 6.8), and from 1.0 (0.0; 6.0) pre-study to 0.0 (0.0; 6.02) in LEOPOLD Kids Part A (n = 18, 35.3%). Octocog alfa was well tolerated, and no patients had drug-related serious AEs or inhibitors.

CONCLUSION: Treatment with octocog alfa prophylaxis appeared to have a favorable risk-benefit profile compared with rFVIII-FS and thus could be an effective and improved alternative strategy for individualized treatment for children, adolescent and adult patients with severe hemophilia A currently on rFVIII-FS treatment.

PMID:37309365 | PMC:PMC10257928 | DOI:10.2147/JBM.S405624

Cureus. 2023 May 11;15(5):e38908. doi: 10.7759/cureus.38908. eCollection 2023 May.

ABSTRACT

Metformin is considered an initial oral pharmacotherapy of choice for treating hyperglycemia in type 2 diabetes mellitus (T2DM). Although safe in the vast majority of the population, rare side effects will come to light as the prevalence of T2DM continues to rise. We present a rare case of metformin-induced hepatotoxicity and possibly the first reported case of dose-dependent metformin-induced hepatotoxicity. This case report aims to make clinicians aware of this infrequent yet significant adverse reaction that can arise with metformin therapy.

PMID:37309348 | PMC:PMC10257557 | DOI:10.7759/cureus.38908

BMC Psychiatry. 2023 Jun 13;23(1):421. doi: 10.1186/s12888-023-04932-4.

ABSTRACT

BACKGROUND: Alexithymia is common and causes serious harm to people living with HIV/AIDS. Therefore, this study aimed to examine its prevalence and associated factors among people living with HIV/AIDS in China.

METHODS: A cross-sectional study was conducted in two designated AIDS medical institutions in Harbin, China between January and December 2019. In total, 767 participants completed the 20-item Toronto Alexithymia Scale, the University of California Los Angeles Loneliness short-form, the Patient Health Questionnaire-9, the HIV Treatment Regimen Fatigue Scale, and the Alcohol Use Disorders Identification Test-Consumption. The participants responded to several questions regarding their demographic characteristics, life satisfaction, disease-related economic burden, and their antiretroviral therapy (ART) side effects. Multivariate logistic regression assessed the relationship between alexithymia and associated factors. Odds ratios (OR) and 95% confidence intervals (CI) for OR were calculated.

RESULTS: Approximately 36.1% of the participants were classified as having alexithymia. After adjusted age and education, the logistic regression model indicated that disease-related economic burden (OR = 1.477, 95% CI = 1.155-1.888), ART side effects (OR = 1.249, 95% CI = 1.001-1.559), loneliness (OR = 1.166, 95% CI = 1.101-1.236), and HIV treatment regimen fatigue (OR = 1.028, 95% CI = 1.017-1.039) were positively associated with alexithymia.

CONCLUSIONS: The mental health problems of people living with HIV/AIDS are essential to understand and deserve attention. Disease-related economic burdens are major associated factors. Multiple actors should provide better services and guarantees for patients.

PMID:37308930 | DOI:10.1186/s12888-023-04932-4

BMC Public Health. 2023 Jun 12;23(1):1116. doi: 10.1186/s12889-023-16041-8.

ABSTRACT

BACKGROUND: We aimed to evaluate the association of sedentary behavior (SB) and moderate to vigorous leisure-time physical activity (MVPA) with sleep quality during the COVID-19 pandemic.

METHODS: Cross-sectional, population-based study in adults, conducted from October to December 2020 in the Iron Quadrangle region, Brazil. The outcome was sleep quality, evaluated with the Pittsburgh Sleep Quality Index. SB was assessed by self-report of total sitting time, before and during the pandemic. Individuals with ≥ 9 h of total sitting time were classified as SB. In addition, the ratio of time spent in MVPA to time in SB was analyzed. A contrasted directed acyclic graph (DAG) model was constructed to adjust logistic regression models.

RESULTS: A total of 1629 individuals were evaluated, the prevalence of SB before the pandemic was 11.3% (95%CI: 8.6-14.8), and during the pandemic 15.2% (95%CI: 12.1-18.9). In multivariate analysis, the chance of poor sleep quality was 77% higher in subjects with SB ≥ 9 h per day (OR: 1.77; 95% CI: 1.02-2.97). Furthermore, a one-hour increase in SB during the pandemic, increased the chance of poor sleep quality by 8% (OR: 1.08; 95%CI 1.01-1.15). In the analysis of the ratio of MVPA per SB in individuals with SB ≥ 9 h, practicing 1 min of MVPA per hour of SB reduces the chance of poor sleep quality by 19% (OR: 0.84; 95%CI: 0.73-0.98).

CONCLUSION: SB during the pandemic was a factor associated with poor sleep quality, and the practice of MVPA can reduce the effects of SB.

PMID:37308867 | DOI:10.1186/s12889-023-16041-8

Acta Pharm. 2023 Jun 12;73(2):293-310. doi: 10.2478/acph-2023-0029. Print 2023 Jun 1.

ABSTRACT

We aimed to identify whether a spontaneous reporting system (SRS) in Croatia could timely identify and confirm signals for COVID-19 vaccines. Post-marketing spontaneous reports of adverse drug reactions (ADRs) following COVID-19 immunisation reported to the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) were extracted and analysed. 6624 cases reporting 30 655 ADRs following COVID-19 immunisation were received from 27th December 2020 to 31st December 2021. Available data in those cases were compared with data available to the EU network at the time when signals were confirmed and minimisation measures were implemented. 5032 cases, reporting 22 524 ADRs, were assessed as non-serious, and 1,592 cases, reporting 8,131 ADRs as serious. The most reported serious ADRs, which were listed in the MedDRA Important medical events terms list, were syncope (n = 58), arrhythmia (n = 48), pulmonary embolism (n = 45), loss of consciousness (n = 43), and deep vein thrombosis (n = 36). The highest reporting rate had Vaxzevria (0.003), followed by Spikevax and Jcovden (0.002), and Comirnaty (0.001). Potential signals were identified, however, they couldn't be timely confirmed solely on cases retrieved by SRS. In order to overcome the limitations of SRS, active surveillance and post-authorisation safety studies of vaccines should be implemented in Croatia.

PMID:37307371 | DOI:10.2478/acph-2023-0029

Acta Pharm. 2023 Jun 12;73(2):195-210. doi: 10.2478/acph-2023-0013. Print 2023 Jun 1.

ABSTRACT

A non-interventional retrospective study in ambulatory patients was conducted at the emergency department of the Division of internal medicine. In 2 months, 266 suspected adverse drug reactions (ADRs) were identified in 224/3453 patients (6.5 %). In 158/3453 patients (4.6 %), an ADR was the reason for emergency department visit and in 49 patients (1.4 %), ADRs led to hospitalisation. A causality assessment algorithm was developed, which included Naranjo algorithm and levels of ADR recognition by the treating physician and the investigators. Using this algorithm, 63/266 ADRs (23.7 %) were classified as "certain", whereas using solely the Naranjo score calculation, only 19/266 ADRs (7.1 %) were assessed as "probable" or "certain", and the rest of ADRs (namely, 247/266 = 92.9 %) were assessed as "possible". There were 116/266 (43.6 %) ADRs related to potential drug-drug interactions (DDIs), stated in at least one of the literature sources used. Based on the causality relationship, the rate of the clinically expressed DDIs was 19.0 %, or 12/63 "certain" ADR cases. Of these, 10 cases presented serious DDI-related ADRs. In summary, ADR causality assessment based exclusively on Naranjo algorithm demonstrated low sensitivity at an ambulatory emergency setting. Additional clinical judgment, including the opinion of the treating physician, proved necessary to avoid under-rating of the causality relationship, and enabled the determination of clinically expressed DDIs.

PMID:37307369 | DOI:10.2478/acph-2023-0013

PLoS One. 2023 Jun 12;18(6):e0280586. doi: 10.1371/journal.pone.0280586. eCollection 2023.

ABSTRACT

BACKGROUND: Although the current guideline recommends the use of high-intensity statin to reduce the low-density lipoprotein cholesterol (LDL-C) level by 50% in patients with baseline value of ≥ 190 mg/dL, direct application of this recommendation to Asian populations is still questionable. This study was performed to investigate the statin response of LDL-C in Korean patients with LDL-C ≥ 190 mg/dL.

METHODS: A total of 1,075 Korean patients (age 60.7 ± 12.2 years, women 68%) with baseline LDL-C ≥ 190 mg/dL without cardiovascular disease was retrospectively reviewed. Lipid profiles at 6 months, side effects and clinical outcomes during the follow-up period after statin treatment were assessed according to statin intensity.

RESULTS: Most of the patients (76.3%) were treated with moderate-intensity statins, 11.4% with high-intensity statins, and 12.3% with a statin + ezetimibe. The reductions in LDL-C percentage at 6 months were 48.0%, 56.0% and 53.3% in patients treated with moderate-intensity statins, high-intensity statins and statin + ezetimibe, respectively (P < 0.001). Side effects requiring dose reduction, medication switch or drug interruption were observed in 1.3%, 4.9% and 2.3% of patients treated with moderate-intensity statin, high-intensity statin and statin + ezetimibe, respectively (P = 0.024). During the median follow-duration of 815 days (interquartile range, 408-1,361 days), the incidences of cardiovascular events were not different among the 3 groups (log-rank P = 0.823).

CONCLUSIONS: Compared to high-intensity statin, moderate-intensity statin was effective enough in reaching target goal of LDL-C without increase in cardiovascular risk and with fewer side effects in Korean patients with LDL-C ≥ 190 mg/dL.

PMID:37307267 | PMC:PMC10259785 | DOI:10.1371/journal.pone.0280586

PLoS One. 2023 Jun 12;18(6):e0287122. doi: 10.1371/journal.pone.0287122. eCollection 2023.

ABSTRACT

Among antipsychotics, clozapine is associated with a high risk of seizures. This study aimed to generate novel hypotheses regarding trends in the onset of clozapine-induced seizures using the JADER (Japanese Adverse Drug Event Report) database. Seizures were defined according to the Standardized MedDRA Queries (SMQ) for convulsions (SMQ20000079). Trends in the onset of clozapine-induced seizures were assessed using multivariate logistic regression analysis with covariates of sex, age, clozapine dose, antipsychotic polypharmacy, concomitant medications, and history of convulsive disorder. In addition, we assessed the time-to-onset of clozapine-induced seizures using the median time, interquartile range, and Weibull shape parameter. The JADER database registered 2,745 cases of adverse events with clozapine, and 1,784 cases were included in the analysis after excluding cases for which clinical information was not available. Medium (200-400 mg) and high (> 400 mg) doses of clozapine had a significantly higher reporting rate of seizures than low doses (< 200 mg) (adjusted reporting odds ratio [aROR] = 3.05, 95% confidence interval [CI]: 1.86-4.99 and aROR = 9.81, 95% CI: 6.06-15.89, respectively). Younger age, antipsychotic polypharmacy, and concomitant use of lithium were also significantly associated with reports of seizures. The time-to-onset analysis of 222 cases of clozapine-induced seizures showed that the median time was 134 (interquartile range, 72-295) days. The 95% CI of the WSP β-value for clozapine-induced seizures included 1 and was classified as a random failure type. In conclusion, the results suggest that clozapine-induced seizures are dose-dependent adverse events that should be monitored with consideration of the effects of age and concomitant medications. Further epidemiological research is needed to strengthen and validate our hypotheses.

PMID:37307250 | PMC:PMC10259781 | DOI:10.1371/journal.pone.0287122

Cancer Treat Res. 2023;185:285-310. doi: 10.1007/978-3-031-27156-4_14.

ABSTRACT

Malnutrition in cancer patients is highly prevalent. The metabolic and physiologic changes associated with the disease and the side effects of treatment regimens all combine together to produce a detrimental effect on the patient's nutritional status. A poor nutritional status significantly reduces the efficacy of treatment methods and the patient's overall chances of survival. Therefore, an individualized nutrition care plan is essential to counter malnutrition in cancer. Nutritional assessment is the first step of this process which sets the foundation for developing an effective intervention plan. Currently, there is no single standard method for nutritional assessment in cancer. Hence, to get a true picture of the patient's nutritional state, a comprehensive analysis of all aspects of the patient's nutritional status is the only reliable strategy. The assessment includes anthropometric measurements and evaluation of body protein status, body fat, inflammation markers, and immune markers. A thorough clinical examination which factors in the medical history and physical signs, along with the dietary intake patterns of the patient, is also important components of nutritional assessment of cancer patients. To facilitate with the process, various nutritional screening tools like patient-generated subjective global assessment (PGSGA), nutrition risk screening (NRS), and malnutrition screening tool (MST) have been developed. While these tools have their own benefits, they only give a glimpse of the nutritional problems and do not bypass the need for a complete assessment employing various methods. This chapter covers all four of the elements of nutritional assessment for cancer patients in detail.

PMID:37306914 | DOI:10.1007/978-3-031-27156-4_14

Cancer Treat Res. 2023;185:207-235. doi: 10.1007/978-3-031-27156-4_11.

ABSTRACT

Considerable advances in the field of cancer have been made; however, these have not been translated into similar clinical progress which results in the high prevalence and increased cancer-related mortality rate worldwide. Available treatments have several challenges such as off-target side effects, non-specific long-term potential biodisruption, drug resistance, and overall inadequate response rates and high probability of recurrence. The limitations associated with independent cancer diagnosis and therapy can be minimized by an emerging interdisciplinary research field of nanotheranostics which include successful integration of diagnosis and therapy on a single agent using nanoparticles. This may offer a powerful tool in developing innovative strategies to enable "personalized medicine" for diagnosis and treatment of cancer. Nanoparticles have been proven to be powerful imaging tools or potent agents for cancer diagnosis, treatment, and prevention. The nanotheranostic provides minimally invasive in vivo visualization of drug biodistribution and accumulation at the target site with real-time monitoring of therapeutic outcome. This chapter intends to cover several important aspects and the advances in the field of nanoparticles-mediated cancer therapeutics including nanocarrier development, drug/gene delivery, intrinsically active nanoparticles, tumor microenvironment, and nanotoxicity. The chapter represents an overview of challenges associated with cancer treatment, rational for nanotechnology in cancer therapeutics, novel concepts of multifunctional nanomaterials for cancer therapy along with their classification and their clinical prospective in different cancers. A special focus is on the nanotechnology: regulatory perspective for drug development in cancer therapeutics. Obstacles hindering further development of nanomaterials-mediated cancer therapy are also discussed. In general, the objective of this chapter is to improve our perceptive in the design and development of nanotechnology for cancer therapeutics.

PMID:37306911 | DOI:10.1007/978-3-031-27156-4_11