Cochrane Database Syst Rev. 2023 Aug 22;8:CD013127. doi: 10.1002/14651858.CD013127.pub2.

ABSTRACT

BACKGROUND: The prevalence of mental health problems is high, and they have a wide-ranging and deleterious effect on many sectors in society. As well as the impact on individuals and families, mental health problems in the workplace negatively affect productivity. One of the factors that may exacerbate the impact of mental health problems is a lack of 'mental health literacy' in the general population. This has been defined as 'knowledge and beliefs about mental disorders, which aid their recognition, management, or prevention'. Mental Health First Aid (MHFA) is a brief training programme developed in Australia in 2000; its aim is to improve mental health literacy and teach mental health first aid strategies. The course has been adapted for various contexts, but essentially covers the symptoms of various mental health disorders, along with associated mental health crisis situations. The programmes also teach trainees how to provide immediate help to people experiencing mental health difficulties, as well as how to signpost to professional services. It is theorised that improved knowledge will encourage the trainees to provide support, and encourage people to actively seek help, thereby leading to improvements in mental health. This review focuses on the effects of MHFA on the mental health and mental well-being of individuals and communities in which MHFA training has been provided. We also examine the impact on mental health literacy. This information is essential for decision-makers considering the role of MHFA training in their organisations.

OBJECTIVES: To examine mental health and well-being, mental health service usage, and adverse effects of MHFA training on individuals in the communities in which MHFA training is delivered.

SEARCH METHODS: We developed a sensitive search strategy to identify randomised controlled trials (RCTs) of MHFA training. This approach used bibliographic databases searching, using a search strategy developed for Ovid MEDLINE (1946 -), and translated across to Ovid Embase (1974 -), Ovid PsycINFO (1967 -), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Common Mental Disorders Group's Specialised Register (CCMDCTR). We also searched online clinical trial registries (ClinicalTrials.gov and WHO ICTRP), grey literature and reference lists of included studies, and contacted researchers in the field to identify additional and ongoing studies. Searches are current to 13th June 2023.

SELECTION CRITERIA: We included RCTs and cluster-RCTs comparing any type of MHFA-trademarked course to no intervention, active or attention control (such as first aid courses), waiting list control, or alternative mental health literacy interventions. Participants were individuals in the communities in which MHFA training is delivered and MHFA trainees. Primary outcomes included mental health and well-being of individuals, mental health service usage and adverse effects of MHFA training. Secondary outcomes related to individuals, MHFA trainees, and communities or organisations in which MHFA training has been delivered DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We analysed categorical outcomes as risk ratios (RRs) and odds ratios (ORs), and continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs), with 95% confidence intervals (CIs). We pooled data using a random-effects model. Two review authors independently assessed the key results using the Risk of Bias 2 tool and applied the GRADE criteria to assess the certainty of evidence MAIN RESULTS: Twenty-one studies involving a total of 22,604 participants were included in the review. Fifteen studies compared MHFA training with no intervention/waiting list, two studies compared MHFA training with an alternative mental health literacy intervention, and four studies compared MHFA training with an active or an attention control intervention. Our primary time point was between six and 12 months. When MHFA training was compared with no intervention, it may have little to no effect on the mental health of individuals at six to 12 months, but the evidence is very uncertain (OR 0.88, 95% CI 0.61 to 1.28; 3 studies; 3939 participants). We judged all the results that contributed to this outcome as being at high risk of bias. No study measured mental health service usage at six to 12 months. We did not find published data on adverse effects. Only one study with usable data compared MHFA training with an alternative mental health literacy intervention. The study did not measure outcomes in individuals in the community. It also did not measure outcomes at our primary time point of six to 12 months. Four studies with usable data compared MHFA training to an active or attention control. None of the studies measured outcomes at our primary time point of six to 12 months.

AUTHORS' CONCLUSIONS: We cannot draw conclusions about the effects of MHFA training on our primary outcomes due to the lack of good quality evidence. This is the case whether it is compared to no intervention, to an alternative mental health literacy intervention, or to an active control. Studies are at high risk of bias and often not sufficiently large to be able to detect differences.

PMID:37606172 | DOI:10.1002/14651858.CD013127.pub2

Pak J Pharm Sci. 2023 Jul;36(4(Special)):1291-1296.

ABSTRACT

The serious adverse effects, such as nephrotoxicity, limit the clinical utility of anticancer doxorubicin (DOX) drug. Cichorium endivia L. is reputed to show antioxidive effectiveness. The present investigation was conducted to explore the nephroprotective potential of crude methanol extract of Cichorium endivia (CECE) pretreatment against DOX-induced nephrotoxicity. Randomly, twenty male Wistar rats were assigned into four groups: Control (no-treatment), DOX group (15mg/kg, i.p, once), DOX + CECE (100mg/kg) and DOX + CECE (200mg/kg). All experiments were performed for 15 consecutive days except for DOX, was delivered once on day twelve. Samples of kidney and serum were collected one day after the last treatment for further assays. Pretreatment with CECE significantly protected the kidney function from DOX toxicity. Urea and creatinine levels were reduced in the serum. Furthermore, CECE administration decreased the damage in the renal histological structure. Restoration of the renal corpuscle and tubules structures was more manifested in a high dose (200mg/kg) of CECE. In summary, these findings demonstrate the nephroprotective effect of CECE pretreatment in DOX-treated rats.

PMID:37606018

Stem Cell Res Ther. 2023 Aug 21;14(1):210. doi: 10.1186/s13287-023-03440-2.

ABSTRACT

INTRODUCTION: Treatments for AGA have yet to produce satisfactory outcomes and may cause intolerable side effects. Recent studies have reported that adipose tissue-derived stem cell conditioned media (ADSC-CM) could induce hair growth and regeneration.

OBJECTIVE: To investigate the efficacy of ADSC-CM combined with minoxidil for hair regeneration therapy in male AGA.

METHODS: This study lasted for 6 weeks. Subjects were divided into two groups: concentrated and non-concentrated ADSC-CM. Scalp was divided vertically in half before intradermal injection was administered from the frontal region of the scalp toward the vertex with a 30G needle, spaced about 1 cm apart. Treatment side received 2 ml of ADSC-CM; the other side was given 2 ml of NaCl 0.9% as placebo. Patients applied 5% minoxidil twice daily post-injection. Improvements were assessed using photographs and trichoscan every 2 weeks.

RESULTS: Hair count, hair density, and mean thickness increased significantly on both sides after 6 weeks, while vellus rate decreased proportionally with the increase of terminal rate. No statistically significant differences between treatment groups were found. Minimum side effects were reported, and subjects were satisfied with the results.

CONCLUSION: Combination of ADSC-CM and minoxidil could be a potential agent for hair regrowth. Follow-up research with extensive populations, longer duration, and different study design may be required to confirm the exact mechanisms of ADSC-CM on hair growth.

TRIAL REGISTRATION: Clinicaltrials.gov, NCT05296863. Registered 25 March 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05296863 .

PMID:37605227 | DOI:10.1186/s13287-023-03440-2

Drugs Aging. 2023 Sep;40(9):857-868. doi: 10.1007/s40266-023-01055-z. Epub 2023 Aug 21.

ABSTRACT

BACKGROUND: Polypharmacy, particularly among older adults, is gaining recognition as an important risk to health. The harmful effects on health arise from disease-drug and drug-drug interactions, the cumulative burden of side effects from multiple medications and the burden to the patient. Single-disease clinical guidelines fail to consider the complex reality of optimising treatments for patients with multiple morbidities and medications. Efforts have been made to develop and implement interventions to reduce the risk of harmful effects, with some promising results. However, the theoretical basis (or pre-clinical work) that informed the development of these efforts, although likely undertaken, is unclear, difficult to find or inadequately described in publications. It is critical in interpreting effects and achieving effectiveness to understand the theoretical basis for such interventions.

OBJECTIVE: Our objective is to outline the theoretical underpinnings of the development of a new polypharmacy intervention: the Team Approach to Polypharmacy Evaluation and Reduction (TAPER).

METHODS: We examined deprescribing barriers at patient, provider, and system levels and mapped them to the chronic care model to understand the behavioural change requirements for a model to address polypharmacy.

RESULTS: Using the chronic care model framework for understanding the barriers, we developed a model for addressing polypharmacy.

CONCLUSIONS: We discuss how TAPER maps to address the specific patient-level, provider-level, and system-level barriers to deprescribing and aligns with three commonly used models and frameworks in medicine (the chronic care model, minimally disruptive medicine, the cumulative complexity model). We also describe how TAPER maps onto primary care principles, ultimately providing a description of the development of TAPER and a conceptualisation of the potential mechanisms by which TAPER reduces polypharmacy and its associated harms.

PMID:37603255 | DOI:10.1007/s40266-023-01055-z

Sci Rep. 2023 Aug 21;13(1):13624. doi: 10.1038/s41598-023-40094-9.

ABSTRACT

Chemotherapy is one of the main treatment options for cancer, but it is usually accompanied with negative side effects. The classical drugs combination with synergistic adjuvants can be the solution to this problem, allowing reducing therapeutic dose. Elucidating the mechanism of adjuvant action is of key importance for the selection of the optimal agent. Here we examine the system drug-adjuvant to explain the observed effect in practice. We used the first line drug cisplatin. Morpholinium and 4-methylpiperazinium 4,5-dichloro isothiazol-3-carboxylates were selected as adjuvants. The study of the cisplatin-adjuvant system was carried out by quantum chemical modeling using DFT. It turned out that adjuvants form conjugates with cisplatin that lead to the relocation of frontier molecular orbitals as well as increase of conjugate's dipole moment. It resulted in change of the interaction character with DNA and increase of the bioactivity of the system. The data obtained are the basis for expanding the studies to include other drugs and adjuvants. Oncologists will have opportunity to use "classical" chemotherapy drugs in combination with synergists for those patients who have not been previously recommended to such a treatment because of pronounced toxic side effects.

PMID:37604841 | PMC:PMC10442360 | DOI:10.1038/s41598-023-40094-9

J Immunother Cancer. 2023 Aug;11(8):e007236. doi: 10.1136/jitc-2023-007236.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the past.

PATIENTS AND METHODS: We used a novel method for long-amplicon next generation sequencing of rearranged TCRB chains from peripheral blood total RNA to evaluate the link between TRBV polymorphisms and irAEs in patients treated with immunotherapy for cancer. We employed multiplex PCR to create amplicons spanning the three beta chain complementarity-determining regions (CDR) regions to enable detection of polymorphism within the germline-encoded framework and CDR1 and CDR2 regions in addition to CDR3 profiling. Resultant amplicons were sequenced via the Ion Torrent and TRBV allele profiles constructed for each individual was correlated with irAE annotations to identify haplotypes associated with severe irAEs (≥ grade 3).

RESULTS: Our study included 81 patients who had irAEs when treated with immunotherapy for cancer. By using principal component analysis of the 81 TRBV allele profiles followed by k-means clustering, we identified six major TRBV haplotypes. Strikingly, we found that one-third of this cohort possessed a TRBV allele haplotype that appeared to be protective against severe irAEs.

CONCLUSION: The data suggest that long-amplicon TCRB repertoire sequencing can potentially identify TRBV haplotype groups that correlate with the risk of severe irAEs. Germline-encoded TRBV polymorphisms may serve as a predictive biomarker of severe irAEs.

PMID:37604642 | DOI:10.1136/jitc-2023-007236

JAMA Netw Open. 2023 Aug 1;6(8):e2329074. doi: 10.1001/jamanetworkopen.2023.29074.

NO ABSTRACT

PMID:37603336 | DOI:10.1001/jamanetworkopen.2023.29074

Med Oncol. 2023 Aug 21;40(9):273. doi: 10.1007/s12032-023-02151-1.

ABSTRACT

Conventional chemotherapy has significant limitations for colorectal cancer (CRC) treatment, especially those who have developed metastatic recurrence CRC. A growing number of studies have investigated the potential use of monoclonal antibodies (mAbs) for CRC therapy. mAbs showing clinical benefits for CRC, making the treatment more selective with lower side effects without significant immunogenicity. In addition, recent advancements in antibody engineering strategies and the development of bifunctional or even trifunctional drugs have helped to overcome heterogeneity as the main challenge in cancer treatment. The current review discusses advances in applying mAbs for CRC therapy alone, combined, or with small molecules.

PMID:37603117 | DOI:10.1007/s12032-023-02151-1

Psychopharmacol Bull. 2023 Aug 11;53(3):61-65.

ABSTRACT

Cannabis is a widely used illicit substance that is historically consumed via smoking, but alternative methods of cannabis consumption have been growing in popularity over the past several decades. One such modality is vaporization, which can appeal specifically to adolescent consumers given these pen devices' ease of concealment, lack of characteristic odor, and marketability. Cannabis products designed for vaping often have higher concentrations of the psychoactive component of cannabis, tetrahydrocannabinol (THC), when compared with traditional cannabis leaf smoking. This can increase the intensity of cannabis-related effects such as analgesia, relaxation, appetite stimulation, and reduced nausea and emesis, but also potentially increases the risk for adverse effects such as dysphoria, and more severely, cannabis-induced psychosis (CIP). Here, we present the case of an adolescent female who was brought after school to our emergency department presenting with symptoms of acute psychosis. Her subsequent workup was effectively normal apart from a urine drug screen positive for THC, which the patient confirmed was due to use of a cannabis pen prior to leaving school that day. This prompted the diagnosis of CIP, which was self-limited and resolved without significant intervention. We use this case to provide the symptomatology and treatment of CIP secondary to cannabis pen use, as well as more broadly discuss the potential implications of cannabis vaping on adolescent neurodevelopment, substance use, and psychiatric comorbidities.

PMID:37601084 | PMC:PMC10434310

Front Immunol. 2023 Aug 3;14:1230893. doi: 10.3389/fimmu.2023.1230893. eCollection 2023.

ABSTRACT

Immunotherapy has developed rapidly in solid tumors, especially in the areas of blocking inhibitory immune checkpoints and adoptive T-cell transfer for immune regulation. Many patients benefit from immunotherapy. However, the response rate of immunotherapy in the overall population are relatively low, which depends on the characteristics of the tumor and individualized patient differences. Moreover, the occurrence of drug resistance and adverse reactions largely limit the development of immunotherapy. Recently, the emergence of nanodrug delivery systems (NDDS) seems to improve the efficacy of immunotherapy by encapsulating drug carriers in nanoparticles to precisely reach the tumor site with high stability and biocompatibility, prolonging the drug cycle of action and greatly reducing the occurrence of toxic side effects. In this paper, we mainly review the advantages of NDDS and the mechanisms that enhance conventional immunotherapy in solid tumors, and summarize the recent advances in NDDS-based therapeutic strategies, which will provide valuable ideas for the development of novel tumor immunotherapy regimen.

PMID:37600822 | PMC:PMC10435760 | DOI:10.3389/fimmu.2023.1230893

Inflammopharmacology. 2023 Aug 21. doi: 10.1007/s10787-023-01264-3. Online ahead of print.

ABSTRACT

This study aimed at determining whether there is a difference in the safety profile between fast release (FR) aspirin tablets and regular galenic formulations of aspirin. This study was based on a clinical study database pool (Bayer HealthCare) including 84 clinical studies and 16,095 human subjects. The meta-analysis included 72 studies applying a single dose of aspirin of at most 1000 mg and was, therefore, based on individual data from 9288 subjects. Of these, 6029 subjects took aspirin and 3259 subjects took placebo. Endpoints were adverse events (AEs) of any kind and, especially of gastrointestinal (GI) nature. Event incidence and odds ratios (OR) based on Mantel-Haenszel risk estimates were calcuated. Subjects on aspirin FR had a significantly decreased OR of 0.65 [0.48, 0.90] [95% confidence interval] for all AEs and of 0.39 [0.20, 0.79] for drug-related all AEs versus placebo. The risk of all GI AEs tended to be reduced for subjects on aspirin FR (0.65 [0.41; 1.03]), but not for drug-related GI AEs. Subject on aspirin mono and aspirin mono (plain only, w/o FR) showed an increased risk of drug-related all AEs compared to placebo (1.34 [1.11; 1.62] and 1.43 [1.13; 1.80]). However, subjects on aspirin FR and those on regular aspirin had almost the same risk of all determined AEs. In conclusion, aspirin FR tablets showed a comparable GI tolerability to regular galenic formulations of aspirin after short-term treatment. Major GI complication did not occur after intake of any galenic formulation of aspirin.

PMID:37603157 | DOI:10.1007/s10787-023-01264-3

J Hypertens. 2023 Aug 15. doi: 10.1097/HJH.0000000000003536. Online ahead of print.

ABSTRACT

OBJECTIVE: Cough caused by angiotensin-converting enzyme inhibitors (ACEIs) limits their clinical application and cardiovascular benefits. This randomized trial investigated whether genotype-guided perindopril use could reduce drug-related cough in 20 to 79-year-old individuals with hypertension.

METHODS: After screening 120 patients and randomization, 68 were assigned to genotyping (n = 41) and control (n = 27) groups. NELL1 p.Arg382Trp (rs8176786) and intron (rs10766756) genotype information was used to subdivide the genotyping group into high-risk and low-risk subgroups with at least one or no risk alleles for ACEI-related cough, respectively. The high-risk subgroup received candesartan (8 mg/day) for 6 weeks, whereas the low-risk subgroup received perindopril (4 mg/day). The control group, which was not genotyped, received perindopril (4 mg/day). The primary outcome variables were cough and moderate/severe cough; the secondary outcome variable was any adverse event.

RESULTS: During the 6-week period, the risk of cough was lower in the genotyping group than in the control group [five (12.2%) and nine (33.3%) participants, respectively; hazard ratio: 0.25; log-rank P = 0.017]. The moderate/severe cough risk was also lower in the genotyping group [one (2.4%) and five (18.5%) participants, respectively; hazard ratio: 0.12; log-rank P = 0.025]. Differences in cough (hazard ratio: 0.56; log-rank P = 0.32) and moderate/severe cough risk (hazard ratio: 0.26; log-rank P = 0.19) between the low-risk and control groups were not significant. The risk of total adverse events was similar between any two groups.

CONCLUSION: Cough risk was lower during genotype-guided treatment than during conventional treatment. These results support the utility of NELL1 variant data in clinical decision making to personalize renin-angiotensin system blocker therapy use.

TRIAL REGISTRATION: ClinicalTrials.gov number: NCT05535595 (retrospectively registered at September 7, 2022).Video Abstract style, http://links.lww.com/HJH/C257.

PMID:37602458 | DOI:10.1097/HJH.0000000000003536

Explor Res Clin Soc Pharm. 2023 Jul 24;11:100313. doi: 10.1016/j.rcsop.2023.100313. eCollection 2023 Sep.

ABSTRACT

Arterial hypertension is a lifelong disease, which management is recognized as the most effective way to reduce cardiovascular mortality. Even though there is extensive evidence on the benefits of lifestyle modification and antihypertensive treatment, many patients with hypertension do not reach blood pressure targets. This paper aims to review the history of antihypertensive treatment of one patient and identify the drug related problems that occurred over the study period. In this case report, the patient's health record was studied, guidelines checked and a semi-structured interview conducted. Drug related problems were identified and possible pharmacist interventions were introduced. Drug related problems that could have contributed to the lack of hypertension control were adherence, side effects and disease-drug interaction. Identified pharmacists' interventions ranged from managing self-medication, to collaboration with general practitioner to change prescribing, and counselling the patient on medication use, including adherence. Even though the drug related problems were not that serious in the studied case, the patient could have valued from pharmacist intervention.

PMID:37601158 | PMC:PMC10433230 | DOI:10.1016/j.rcsop.2023.100313

Res Pract Thromb Haemost. 2023 Jun 22;7(5):100283. doi: 10.1016/j.rpth.2023.100283. eCollection 2023 Jul.

ABSTRACT

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect from unfractionated or low-molecular-weight heparin that results in thrombocytopenia and potentially catastrophic thrombosis. HIT occurs due to the development of platelet-activating antibodies against multimolecular complexes of platelet factor 4 and heparin. Given the frequency of thrombocytopenia and heparin use among hospitalized patients, calculation of the 4Ts Score is recommended to identify patients at increased likelihood of HIT and direct further evaluation. In patients with an intermediate or high probability 4Ts Score, an immunoassay and functional assay are recommended to confirm or refute the diagnosis of HIT. Heparin avoidance and initiation of nonheparin anticoagulation are the mainstays of acute HIT management. In this illustrated review, we provide visual summaries of the diagnosis and management of HIT, highlighting connections between pathophysiology and clinical care as well as summarizing efforts in quality improvement in the field. We further emphasize common pitfalls and pearls in diagnosis and management to encourage evidence-based care. We include graphical representation of the unique challenges of HIT with cardiopulmonary bypass and also delineate autoimmune HIT and its subtypes.

PMID:37601013 | PMC:PMC10439402 | DOI:10.1016/j.rpth.2023.100283

Front Immunol. 2023 Aug 4;14:1223062. doi: 10.3389/fimmu.2023.1223062. eCollection 2023.

ABSTRACT

Hemophagocytic lymphohistiocytosis (HLH) is a severe and life-threatening hyperinflammatory condition characterized by excessive activation of macrophages and T cells and resulted in multi-organ dysfunction. HLH can be a primary disease or secondary to infections, malignancy, and some autoimmune diseases, including adult-onset Still's disease (AOSD) and systemic lupus erythematosus (SLE). However, it is rare for HLH to occur as a secondary condition to drug-induced lupus erythematosus (DILE). In this report, we present a case of HLH as an unusual complication during SLE treatment in a 31-year-old male patient. The patient initially suffered from active chronic hepatitis B (CHB) and was treated with pegylated INFα-2b (Peg-INFα-2b), tenofovir disoproxil and lamivudine. After 19 months, CHB obtained biochemical and virological response with HBsAg positive to HBsAb. The patient developed fever, headache, and cytopenia after Peg-INFα-2b treatment for 33 months, and laboratory studies revealed that ANA and anti dsDNA were positive. He displayed 5 features meeting the HLH-2004 criteria for diagnosis including fever, pancytopenia, hyperferritinemia, high levels of soluble CD25, and hemophagocytosis on bone marrow biopsy. The patient was initiated with a combination treatment of intravenous methylprednisolone pulse therapy, oral cyclosporine, and etoposide (VP-16), which was followed by a course of oral prednisolone, intravenous cyclophosphamide pulse therapy, and entecavir with complete response. To our knowledge, this is the first report of IFN-α induced SLE complicating with HLH. Physicians should consider the potential autoimmune side effects of IFN-α therapy and be alert to insidious HLH in patients diagnosed with SLE.

PMID:37600795 | PMC:PMC10436618 | DOI:10.3389/fimmu.2023.1223062

Oncol Lett. 2023 Jul 28;26(3):398. doi: 10.3892/ol.2023.13984. eCollection 2023 Sep.

ABSTRACT

Drug-induced thrombocytopenia is an adverse reaction characterized by accelerated platelet destruction. The present study described a case of thrombocytopenia that occurred during treatment with panitumumab. A female patient aged 49 years with metastatic rectal adenocarcinoma was treated with 9 out of 12 cycles of therapy with the standard of care, 5-fluorouacil (5-FU), oxaliplatin and folic acid, in association with panitumumab. During cycle 10, the patient developed severe thrombocytopenia, so the therapy was adjusted to a lower dosage; however, during cycle 11, after administration of panitumumab and before administration of 5-FU or oxaliplatin, the patient again presented with severe thrombocytopenia, with a platelet count <2×109/l. Immunology test results were negative apart from anti-nucleus antibodies (titration, 1:160). Naranjo's algorithm was used to establish the relationship between the use of panitumumab and thrombocytopenia onset and a score of 6 ('probable') was found. The temporal link between the onset of symptoms and administration of therapy, the relapse of thrombocytopenia after re-administration of the drug during cycle 11 (positive rechallenge) and Naranjo score of 6 ('probable') are crucial elements for establishing the causal relationship and the probability that thrombocytopenia was related to the administration of panitumumab. The patient then underwent two cycles of therapy with 5-FU, folic acid and irinotecan, in association with bevacizumab, experiencing again the same adverse event. Treatment with monoclonal antibodies was suspended altogether in favor of a switch to trifluridine/tipiracil. No other serious adverse events were reported.

PMID:37600345 | PMC:PMC10433710 | DOI:10.3892/ol.2023.13984

Front Cardiovasc Med. 2023 Aug 4;10:1156980. doi: 10.3389/fcvm.2023.1156980. eCollection 2023.

ABSTRACT

OBJECTIVES: Over the years, it has been found that colchicine offers substantial benefits in secondary prevention in patients with coronary artery disease (CAD). We studied the effects of colchicine timing because there are no guidelines about when to provide it during the perioperative period for patients with CAD.

METHODS: Up to January 1, 2023, seven electronic literature databases were screened (including three English databases and four Chinese databases). Randomized controlled trials included only treatment with colchicine in the perioperative period of CAD. The Cochrane Evaluation Tool was used to judge the risk of bias in research. Statistical analysis was performed by Stata 16.0 software.

RESULTS: We evaluated twelve studies that found colchicine to be effective in decreasing the occurrence of major adverse cardiac events (MACEs) (p < 0.00001), but it also raised the rate of adverse events (p = 0.001). Subgroup analysis showed the same benefit in lowering the incidence of MACE with continuous administration of a total daily dose of 0.5 mg postoperatively while minimizing drug-related side effects in the patients (p = 0.03). When it comes to preventing surgical stroke occurrences, postoperative administration is more effective (p = 0.006). While the effect of simultaneous preoperative and postoperative administration was marginally greater than other periods in reducing postoperative hs-CRP levels (p = 0.02).

CONCLUSION: Colchicine, a traditional anti-inflammatory drug, also reduces the risk of MACE by reducing inflammation after PCI. Administration at different periods had no significant effect on decreasing the occurrence of MACE, but when administered postoperatively, we advise continuous administration with a total daily dose of 0.5 mg to obtain the same benefit while minimizing the drug's side effects. Postoperative administration is the better measure to prevent postoperative stroke events. Due to the effective anti-inflammatory effect of colchicine, we recommend its use as early as possible in the perioperative period and its continued use at low doses in the postoperative period.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316751, identifier CRD42022316751.

PMID:37600022 | PMC:PMC10438985 | DOI:10.3389/fcvm.2023.1156980

Gynecol Endocrinol. 2023 Dec;39(1):2247093. doi: 10.1080/09513590.2023.2247093.

ABSTRACT

The debate about contraception has become increasingly important as more and more people seek safe and effective contraception. More than 1 billion women of reproductive age worldwide need a method of family planning, and wellbeing, socio-economic status, culture, religion and more influence the reasons why a woman may ask for contraception. Different contraceptive methods exist, ranging from 'natural methods' (fertility awareness-based methods - FABMs) to barrier methods and hormonal contraceptives (HCs). Each method works on a different principle, with different effectiveness.FABMs and HCs are usually pitted against each other, although it's difficult to really compare them. FABMs are a valid alternative for women who cannot or do not want to use hormone therapy, although they may have a high failure rate if not used appropriately and require specific training. HCs are commonly used to address various clinical situations, although concerns about their possible side effects are still widespread. However, many data show that the appropriate use of HC has a low rate of adverse events, mainly related to personal predisposition.The aim of this review is to summarize the information on the efficacy and safety of FABMs and HCs to help clinicians and women choose the best contraceptive method for their needs.

PMID:37599373 | DOI:10.1080/09513590.2023.2247093

Intern Med J. 2023 Aug;53(8):1485-1488. doi: 10.1111/imj.16194.

ABSTRACT

There is a growing interest in the appropriate evaluation of penicillin adverse drug reaction (ADR) labels. We have developed machine learning models for classifying penicillin ADR labels using free-text reaction descriptions, and here report external and practical validation. The models performed comparably with expert criteria for the categorisation of allergy or intolerance and identification of high-risk allergies. These models have practical applications in detecting individuals suitable for penicillin ADR evaluation. Implementation studies are required.

PMID:37599225 | DOI:10.1111/imj.16194

Oncology. 2023 Aug 18. doi: 10.1159/000533420. Online ahead of print.

ABSTRACT

INTRODUCTION: The release of tumor-associated antigens with cytotoxic chemotherapy treatment may enhance the response to immune checkpoint blockade. Eribulin is a microtubule inhibitor with proven overall survival (OS) benefit in metastatic breast cancer (MBC), which may also enhance intratumoral vascular remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed cell death ligand-1 (PD-L1) receptor. This study sought to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of eribulin in combination with durvalumab, as well as the safety and preliminary antitumor activity of the combination in patients with previously treated HER2-negative (HER2-) MBC and recurrent ovarian cancer (ROC).

METHODS: Cohorts of 3-6 patients with HER2- MBC and ROC were treated in a modified 3+3 design. Eligible patients received escalating doses of eribulin (1.1mg/m2 or 1.4 mg/m2 IV on day 1 and day 8) with durvalumab (1.12g IV on day 1) in 21-day cycles until dose-limiting toxicity (DLT), intolerable adverse events (AEs), disease progression, or other reasons for withdrawal.

PRIMARY ENDPOINT: the rate of dose limiting toxicities (DLTs) during cycle 1 and 2 of therapy. Secondary endpoints: AE rate, Objective Response Rate (ORR), progression-free survival (PFS), and OS.

RESULTS: Nine patients with a median of 4 prior therapies for advanced disease were treated: 5 patients with HER2- MBC (1 with triple negative disease and 4 with hormone positive disease) and 4 patients with ROC. The RP2D of eribulin was 1.4mg/m2 in combination with durvalumab. There were no DLTs experienced during the first two cycles of therapy. The most common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, and nausea; most were grade 1 or 2. There was one immune-related AE of grade 3 (hepatitis) after 5 cycles of treatment, for which patient came off study. Two other patients discontinued study drug related to toxicity [neutropenia (n=1), hepatic toxicity (n=1)]. ORR was 55% and 4 additional patients experienced 3 stable disease. All MBC patients exhibited a response to therapy. Median PFS was 6.2 months. Median OS was 15.0 months.

CONCLUSION: The combination of eribulin at a dose of 1.4 mg/m2 with standard dose durvalumab had a favorable AE profile in patients with previously treated HER2- MBC and ROC. The early anti-tumor activity observed in all MBC patients enrolled in the study suggests that further investigation of this combination is warranted.

PMID:37598677 | DOI:10.1159/000533420