J Oncol Pharm Pract. 2023 Jul 27:10781552231189819. doi: 10.1177/10781552231189819. Online ahead of print.

ABSTRACT

INTRODUCTION: Autoimmune side effects can be detected during the use of BRAF/MEK inhibitor. Although its frequency, mechanism and importance are not known exactly, there are cases reported in the literature.

CASE REPORT: We report a case of drug-induced vitiligo in a patient with metastatic conjunctival malignant melanoma who was treated with BRAF/MEK inhibition therapy.

MANAGEMENT AND OUTCOME: In the case, vitiligo was controlled with topical treatments. Follow-up process of the patient has been continuing with no progression on month 12 of the current treatment.

DISCUSSION: Although ICI-related autoimmune side effects and vitiligo have been described more frequently, vitiligo may also occur secondary to BRAK/MEK inhibition. This case also points out that cutaneous toxicity is manageable with no delay in treatment thanks to collaboration of dermatologists and oncologists.

PMID:37499639 | DOI:10.1177/10781552231189819

Int Immunopharmacol. 2023 Jul 25;123:110663. doi: 10.1016/j.intimp.2023.110663. Online ahead of print.

ABSTRACT

Drug complication is still considered as one of the most important causes of death and drug in-compliance around the world. In this cross sectional study, 372 people living with HIV (PLHIV) above 16 years were enrolled. The drug complication was extracted based on the information of the patient's file. The molecular test was performed by the Restriction Fragment length polymorphism-Polymerase Chain Reaction method. Allelic frequency, haplotype analyses, linkage disequilibrium and odds ratio (OR) were calculated. The linear regression model was used to analyze the association of IL'SNPs with drug complication after adjustment for age and sex. Drug complications were observed in 150(40.3%) participants. The most common drug complications were hematological 94(62.7%) ones. The SNPs- rs 2275913 and rs763780- of IL-17were in complete linkage (D́ = 1 and r = 1). A-A haplotype of IL-17 in SNPs- rs 2275913 and rs763780 can increase the risk of drug complication up to 1.628 times more than other haplotypes and G-G and G-A haplotypes have a protective role among them 0.268 and 0.628 times, respectively. Our result for the first time demonstrated the role of IL-17 polymorphism in induced antiretroviral drug complication incidence. Probably A-A haplotype could increase the immune response to anti-retroviral drugs, and G-G and A-G haplotypes can decrease it.

PMID:37499393 | DOI:10.1016/j.intimp.2023.110663

JMIR Public Health Surveill. 2023 Jul 27;9:e46767. doi: 10.2196/46767.

ABSTRACT

BACKGROUND: HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy.

OBJECTIVE: This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection.

METHODS: PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework.

RESULTS: We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I2=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I2=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I2=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I2=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs.

CONCLUSIONS: LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.

PMID:37498645 | DOI:10.2196/46767

Discov Oncol. 2023 Jul 27;14(1):139. doi: 10.1007/s12672-023-00747-7.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent diagnosed malignancies and one of the leading causes of cancer-related deaths worldwide. 5-Fluorouracil (5-FU) and its combination regimen are commonly used as primary chemotherapeutic agents for advanced CRC. Intestinal mucositis is one of the most frequent side effects of 5-FU. Artesunate (Arte) is derived from the wormwood plant Artemisia annua. Arte is not only effective against malaria but also diabetes, atherosclerosis, inflammation, and other conditions. The mechanism by which 5-FU damages the intestinal tract is unclear, and there is no standard treatment for diarrhea caused by 5-FU. Therefore, it is critical to discover novel and promising therapeutic drugs for 5-FU side effect treatment.

METHODS: The morphology and expression of genes and proteins associated with the aging of HUVECs, HIECs, and intestinal tissues were compared to the those of the control group. The cell lines and tissues were evaluated by SA-β-Gal staining, Western blotting, and RT‒qPCR. HIEC and HCT116 cell viability was assessed in vitro by a CCK-8 assay and in vivo by a subcutaneous tumor mouse assay. Tumor cell proliferation and apoptosis was evaluated by immunohistochemistry.

RESULTS: Here, we report that Arte alleviates the adverse side effects caused by 5-FU in intestinal tissue, and that 5-FU-induced intestinal damage is associated with drug-induced chemical inflammation and an increase in the proportion of senescent cells. Arte decreases the ratio of SA-β-Gal-positive cells and downregulated the expression of aging-related proteins (p53, p16) and aging-related genes (p53, p21). Mechanistically, Arte relieves intestinal injury by inhibiting mTOR expression, which is associated with the regulation of aging. Moreover, Arte suppresses the p38MAPK and NF-κB signaling pathways, which are related to inflammation regulation. In addition, the combined therapy of Arte plus 5-FU significantly decreases cancer cell viability in vitro. Arte and 5-FU synergistically reduce the growth of colorectal cancer (CRC) xenografts in vivo.

CONCLUSIONS: Overall, our findings point to the crucial treatment effect of Arte on inflammation, intestinal cell senescence, and CRC cell proliferation and offer a new option for CRC treatment.

PMID:37498338 | DOI:10.1007/s12672-023-00747-7

Open Forum Infect Dis. 2023 Jun 13;10(7):ofad314. doi: 10.1093/ofid/ofad314. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: The prevention of coronavirus disease 2019 (COVID-19) in vulnerable populations is a global health priority. EVADE was a phase 2/3 multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended-half-life monoclonal antibody, for postexposure (PEP) and pre-exposure prophylaxis (PrEP) of symptomatic COVID-19.

METHODS: Eligible participants (vaccine-naive, aged ≥12 years) were randomized 1:1 to receive a single 300-mg intramuscular injection of adintrevimab or placebo. Primary efficacy end points were reverse transcription polymerase chain reaction (RT-PCR)-confirmed symptomatic COVID-19 through day 28 in the PEP cohort (RT-PCR-negative at baseline) and through month 3 in the PrEP cohort (RT-PCR-negative and seronegative at baseline) among participants randomized before emergence of the severe acute respiratory syndrome coronavirus 2 Omicron variant (November 30, 2021). Safety was assessed through 6 months.

RESULTS: Between April 27, 2021, and January 11, 2022, 2582 participants were randomized. In the primary efficacy analysis, RT-PCR-confirmed symptomatic COVID-19 occurred in 3/175 (1.7%) vs 12/176 (6.8%) adintrevimab- and placebo-treated PEP participants, respectively (74.9% relative risk reduction [RRR]; standardized risk difference, -5.0%; 95% CI, -8.87% to -1.08%; P = .0123) and in 12/752 (1.6%) vs 40/728 (5.5%) adintrevimab- and placebo-treated PrEP participants, respectively (71.0% RRR; standardized risk difference, -3.9%; 95% CI, -5.75% to -2.01%; P < .0001). In a prespecified exploratory analysis of 428 PrEP participants randomized after the emergence of Omicron, adintrevimab reduced RT-PCR-confirmed symptomatic COVID-19 by 40.6% (standardized risk difference -8.4%; 95% CI, -15.35% to -1.46%; nominal P = .0177) vs placebo. Adintrevimab was well tolerated, with no serious drug-related adverse events reported.

CONCLUSIONS: A single intramuscular injection of adintrevimab provided prophylactic efficacy against COVID-19 due to susceptible variants without safety concerns. Clinical trial registration. NCT04859517.

PMID:37496612 | PMC:PMC10368201 | DOI:10.1093/ofid/ofad314

Br J Nurs. 2023 Jul 27;32(14):678-682. doi: 10.12968/bjon.2023.32.14.678.

ABSTRACT

Depression and anxiety are common, with one in six people experiencing symptoms in any given week. Of these people, 8.32 million are prescribed antidepressants. People living with HIV are likely to experience psychiatric disorder, with one in three experiencing depression and anxiety, and being at greater risk of developing post-traumatic stress disorder. Sexual side-effects of psychotropic medication are very common, cause distress, and can persist even after the medication has been withdrawn. Antidepressants are powerful drugs and can have severe interactions with many other substances. This article seeks to raise awareness of sexual side-effects of psychotropic medications and draw attention to ethical issues related to post selective serotonin reuptake inhibitor sexual dysfunction (PSSD). Additional risk factors and interactions between psychotropic medications and recreational drugs are identified. Recommendations are made to improve care and clinical outcomes through the development of therapeutic alliances.

PMID:37495413 | DOI:10.12968/bjon.2023.32.14.678

BMJ. 2023 Jul 26;382:p1717. doi: 10.1136/bmj.p1717.

NO ABSTRACT

PMID:37495240 | DOI:10.1136/bmj.p1717

Radiol Clin North Am. 2023 Sep;61(5):913-932. doi: 10.1016/j.rcl.2023.04.010. Epub 2023 May 23.

ABSTRACT

The availability of effective immunosuppressive medication is primarily responsible for the dramatic improvement in long-term graft survival rates after solid organ transplantation. The commonly used drugs include monoclonal/polyclonal antibodies, corticosteroids, calcineurin inhibitors (cyclosporine and tacrolimus), antimetabolites, mammalian target of rapamycin, and many novel drugs. Prolonged immunosuppression is accompanied by several well-described potentially life-threatening complications. In addition to drug-related side effects, recipients of solid organs are unavoidably at a higher risk for infections and malignancies. Select infections and malignancies in solid organ transplant patients have distinctive imaging findings, and radiologists play a crucial role in the timely diagnosis and management of these conditions.

PMID:37495297 | DOI:10.1016/j.rcl.2023.04.010

Lancet HIV. 2023 Jul 21:S2352-3018(23)00151-0. doi: 10.1016/S2352-3018(23)00151-0. Online ahead of print.

ABSTRACT

BACKGROUND: For most adults with HIV-1 and hepatitis B virus (HBV) coinfection, initial recommended treatment is a tenofovir-containing antiretroviral regimen, but no randomised studies have compared tenofovir disoproxil fumarate with tenofovir alafenamide. We aimed to investigate whether bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for viral suppression in individuals with HIV-1 and HBV coinfection at 48 and 96 weeks.

METHODS: We did this randomised, double-blind, active-controlled, phase 3, non-inferiority trial at 46 outpatient centres in China, Dominican Republic, Hong Kong, Japan, Malaysia, South Korea, Spain, Taiwan, Thailand, Turkey, and the USA. Eligible participants were treatment-naive adults (aged ≥18 years) with plasma HIV-1 RNA of at least 500 copies per mL and plasma HBV DNA of at least 2000 IU/mL. Participants were randomly assigned (1:1) to receive daily oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or dolutegravir 50 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg, each with corresponding matching placebo. Randomisation was stratified by hepatitis B e antigen (HBeAg) status (positive vs negative), HBV DNA (<8 vs ≥8 log10 IU/mL), and CD4 count (<50 vs ≥50 cells per μL) at screening. All investigators, participants, and staff providing treatment, assessing outcomes, and collecting data were masked to study treatment for 96 weeks. Coprimary endpoints were the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL (defined by the US Food and Drug Administration snapshot algorithm) and plasma HBV DNA less than 29 IU/mL (using the missing-equals-failure approach) at week 48, with a prespecified non-inferiority margin of -12%. Coprimary endpoints were assessed in the full analysis set, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline HIV-1 RNA or HBV DNA result while on study drug. Safety endpoints were assessed in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03547908.

FINDINGS: Between May 30, 2018 and March 16, 2021, 381 participants were screened, of whom 243 initiated treatment (121 in the receive bictegravir, emtricitabine, and tenofovir alafenamide group; 122 in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group). At week 48, both endpoints met the criteria for non-inferiority: 113 (95%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 111 (91%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HIV-1 RNA less than 50 copies per mL (difference 4·1, 95% CI -2·5 to 10·8; p=0·21), and 75 (63%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus 53 (43%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HBV DNA suppression (difference 16·6, 5·9 to 27·3; nominal p=0·0023). Drug-related adverse events up to week 96 occurred in 35 (29%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 34 (28%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group. One (1%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group reported a serious adverse event (cryptococcal meningitis attributed to immune reconstitution inflammatory syndrome) that was deemed to be treatment-related.

INTERPRETATION: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is an effective therapy for adults with HIV-1 and HBV coinfection starting antiviral therapy.

FUNDING: Gilead Sciences.

PMID:37494942 | DOI:10.1016/S2352-3018(23)00151-0

N Engl J Med. 2023 Jul 27;389(4):309-321. doi: 10.1056/NEJMoa2301940.

ABSTRACT

BACKGROUND: Narcolepsy type 1 is caused by severe loss or lack of brain orexin neuropeptides.

METHODS: We conducted a phase 2, randomized, placebo-controlled trial of TAK-994, an oral orexin receptor 2-selective agonist, in patients with narcolepsy type 1. Patients with confirmed narcolepsy type 1 according to clinical criteria were randomly assigned to receive twice-daily oral TAK-994 (30 mg, 90 mg, or 180 mg) or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (range, 0 to 40 minutes; normal ability to stay awake, ≥20 minutes). Secondary end points included the change in the Epworth Sleepiness Scale (ESS) score (range, 0 to 24, with higher scores indicating greater daytime sleepiness; normal, <10) and the weekly cataplexy rate.

RESULTS: Of the 73 patients, 17 received TAK-994 at a dose of 30 mg twice daily, 20 received 90 mg twice daily, 19 received 180 mg twice daily, and 17 received placebo. The phase 2 trial and an extension trial were terminated early owing to hepatic adverse events. Primary end-point data were available for 41 patients (56%); the main reason for missing data was early trial termination. Least-squares mean changes to week 8 in average sleep latency on the MWT were 23.9 minutes in the 30-mg group, 27.4 minutes in the 90-mg group, 32.6 minutes in the 180-mg group, and -2.5 minutes in the placebo group (difference vs. placebo, 26.4 minutes in the 30-mg group, 29.9 minutes in the 90-mg group, and 35.0 minutes the 180-mg group; P<0.001 for all comparisons). Least-squares mean changes to week 8 in the ESS score were -12.2 in the 30-mg group, -13.5 in the 90-mg group, -15.1 in the 180-mg group, and -2.1 in the placebo group (difference vs. placebo, -10.1 in the 30-mg group, -11.4 in the 90-mg group, and -13.0 in the 180-mg group). Weekly incidences of cataplexy at week 8 were 0.27 in the 30-mg group, 1.14 in the 90-mg group, 0.88 in the 180-mg group, and 5.83 in the placebo group (rate ratio vs. placebo, 0.05 in the 30-mg group, 0.20 in the 90-mg group, and 0.15 in the 180-mg group). A total of 44 of 56 patients (79%) receiving TAK-994 had adverse events, most commonly urinary urgency or frequency. Clinically important elevations in liver-enzyme levels occurred in 5 patients, and drug-induced liver injury meeting Hy's law criteria occurred in 3 patients.

CONCLUSIONS: In a phase 2 trial involving patients with narcolepsy type 1, an orexin receptor 2 agonist resulted in greater improvements on measures of sleepiness and cataplexy than placebo over a period of 8 weeks but was associated with hepatotoxic effects. (Funded by Takeda Development Center Americas; TAK-994-1501 and TAK-994-1504 ClinicalTrials.gov numbers, NCT04096560 and NCT04820842.).

PMID:37494485 | DOI:10.1056/NEJMoa2301940

Cureus. 2023 Jun 24;15(6):e40890. doi: 10.7759/cureus.40890. eCollection 2023 Jun.

ABSTRACT

Increasingly complex and constantly emerging cancer treatment protocols are associated with kidney toxicities. Data clearly demonstrate that when patients with cancer develop acute or chronic kidney disease, severe fluid and electrolyte abnormalities, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. We present a case of a 74-year-old woman with metastatic, recurrent ER+/PR-/HER2+ invasive ductal carcinoma of the right breast, status post bilateral mastectomies, chemotherapy, radiation therapy, and hormonal therapies, who were clinically stable on Trastuzumab/Pertuzumab maintenance for about a year. She then experienced disease progression. She was started on Trastuzumab+Deruxtecan (T-Dxt). However, due to worsening diarrhea of more than 12 episodes per day, decreased oral intake, weakness and weight loss, she got admitted to the hospital. Laboratory data showed hyponatremia, hypokalemia, non-anion gap metabolic acidosis, hypomagnesemia, and hypophosphatemia. These laboratory abnormalities were initially attributed to diarrhea. Renal losses were suspected when the electrolyte abnormalities did not correct despite improving diarrhea. Urine electrolytes were hence tested. There was evidence of Fanconi syndrome with glucosuria, proteinuria, and renal potassium and phosphorus wasting. Fanconi syndrome was attributed to the Deruxtecan component of the combination chemotherapy, as she was previously on Trastuzumab with no such abnormalities. The electrolyte abnormalities resolved over the course of a few months. To our knowledge, this is the first case of Fanconi syndrome due to T-Dxt.

PMID:37492824 | PMC:PMC10364456 | DOI:10.7759/cureus.40890

Front Immunol. 2023 Jul 10;14:1203621. doi: 10.3389/fimmu.2023.1203621. eCollection 2023.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are the standard treatment for metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H). Among immune-related adverse events (irAEs), drug-induced sarcoidosis-like reactions (DISR) are often difficult to differentiate from cancer progression.

MAIN BODY: This is a case of a woman in her mid-60s, with mCRC (RAS wild/BRAF mutant/MSI-H) and abdominal lymph node metastasis, treated with four courses of ipilimumab + nivolumab every 3 weeks, followed by nivolumab every 2 weeks as third-line treatment. After treatment, the original lymph node metastases shrank, but hilar/mediastinal lymph nodes appeared. Endoscopic ultrasound-guided fine-needle aspiration of these lymph nodes revealed multiple epithelioid granulomas without necrosis, indicating a sarcoidosis-like reaction. Fluorodeoxyglucose-positron emission tomography scan showed abnormal subcutaneous accumulation in bilateral forearms and bilateral knee joints. Biopsy of the cutaneous lesions was also performed, which revealed epithelioid granulomas. As the patient had no symptoms in other organs, no specific therapeutic intervention was administered. After the discontinuation of immunotherapy, the sarcoidosis-like reaction regressed without cancer relapse.

CONCLUSIONS: Clinicians should be aware of the possibility of DISR as an irAE during the ICI treatment of mCRC. In suspected cases of DISR following ICI therapy, it is important to differentiate between cancer progression and DISR through histological diagnosis for the subsequent strategy, as radiological and serological findings are not definitive.

PMID:37492584 | PMC:PMC10365267 | DOI:10.3389/fimmu.2023.1203621

Pharmacoepidemiol Drug Saf. 2023 Jul 25. doi: 10.1002/pds.5668. Online ahead of print.

ABSTRACT

BACKGROUND: The disease burden of parkinsonism is extremely costly in the United States. Unlike Parkinson's disease, drug-induced parkinsonism (DIP) is acute and reversible; exploring the causative drug is important to prevent DIP in patients at high-risk of parkinsonism.

OBJECTIVE: To examine whether the use of gastrointestinal (GI) prokinetics is associated with an increased risk of parkinsonism.

METHODS: We conducted a case-crossover study using nationally representative data. We included patients who were newly diagnosed with parkinsonism (ICD-10 G20, G21.1, G25.1) between January 1, 2007 and December 1, 2015. The first prescription date of G20, G21.1, or G25.1 diagnoses was defined as the index date (0 day). Patients with prior extrapyramidal and movement disorders or brain tumors were excluded. We assessed the exposure within the risk (0-29 days) and control periods (60-89 days), before or on the index date. Conditional logistic regression estimated the adjusted odds ratio (aOR) for parkinsonism.

RESULTS: Overall, 2268 and 1674 patients were exposed to GI prokinetics during the risk and control periods, respectively. The use of GI prokinetics significantly increased the occurrence of parkinsonism (aOR = 2.31; 95% Confidence Interval [CI], 2.06-2.59). The use of GI prokinetics was associated with a higher occurrence of parkinsonism in elderly patients (≥65 years old; aOR = 2.69; 95% CI, 2.30-3.14) than in younger patients (aOR = 1.90; 95% CI, 1.59-2.27).

CONCLUSIONS: The use of GI prokinetics was significantly associated with higher occurrences of parkinsonism, necessitating close consideration when using GI prokinetics.

PMID:37491627 | DOI:10.1002/pds.5668

BMJ Open. 2023 Jul 25;13(7):e070405. doi: 10.1136/bmjopen-2022-070405.

ABSTRACT

INTRODUCTION: A prescribing cascade occurs when a drug is prescribed to manage the often unrecognised side effect of another drug; these cascades are of particular concern for older adults who are at heightened risk for drug-related harm. It is unknown whether, and to what extent, gender bias influences physician decision-making in the context of prescribing cascades. The aim of this transnational study is to explore the potential impact of physician implicit gender biases on prescribing decisions that may lead to the initiation of prescribing cascades in older men and women in two countries, namely: Canada and Italy.

METHODS AND ANALYSIS: Male and female primary care physicians at each site will be randomised 1:1 to a case vignette that features either a male or female older patient who presents with concerns consistent with the side effect of a medication they are taking. During individual interviews, while masked to the true purpose of the study, participants will read the vignette and use the think-aloud method to describe their ongoing thought processes as they consider the patient's concerns and determine a course of action. Interviews will be recorded, transcribed verbatim and thematic analysis will be conducted to highlight differences in decisions in the interviews/transcripts, using a common analytical framework across the sites.

ETHICS AND DISSEMINATION: This study has received ethics approval at each study site. Verbal informed consent will be received from participants prior to data collection and all data will be deidentified and stored on password-protected servers. Results of this study will be disseminated through peer-reviewed journal articles and presented at relevant national and international conferences.

PMID:37491093 | DOI:10.1136/bmjopen-2022-070405

J Korean Med Sci. 2023 Jul 24;38(29):e219. doi: 10.3346/jkms.2023.38.e219.

ABSTRACT

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) of the bowel wall has been suggested as an alternative imaging modality for the follow-up of children with Crohn's disease. To demonstrate the feasibility and clinical usefulness of CEUS in the estimation of Crohn's disease activity in children with endoscopy as the reference standard.

METHOD: In this prospective study, 30 pediatric patients with Crohn's disease (24 males and 6 females; median age 14 years) underwent CEUS from December 2020 to August 2021. The simple endoscopic score for Crohn's disease, pediatric Crohn's disease activity index, serologic inflammatory markers, fecal calprotectin and CEUS perfusion parameters were assessed and compared between the inactive and active group based on endoscopic findings.

RESULTS: CEUS was performed successfully in all 30 patients. Two patients showed mild adverse side effects such as temporary dysosmia. The active Crohn's disease group showed higher erythrocyte sedimentation rate (mm/hr) (13.0 vs. 2.0, P = 0.003), C-reactive protein (mg/dL) (4.7 vs. 0.55, P = 0.018) and fecal calprotectin (mcg/g) (1,503 vs. 237.5, P = 0.005). Among the quantitative parameters for CEUS, the mean gradient to the peak value was higher in the active group (1.18 vs. 0.93, P = 0.034). The sensitivity and specificity of the mean gradient to the peak value for predicting active Crohn's disease was 55.6% and 83.3%, respectively, with a cut-off of 1.09 (P = 0.015).

CONCLUSION: CEUS can be a safe and specific diagnostic modality for Crohn's disease activity in children. Among quantitative CEUS parameters, the mean gradient to the peak value could be used to differentiate active and inactive Crohn's disease.

PMID:37489715 | DOI:10.3346/jkms.2023.38.e219

J Nepal Health Res Counc. 2023 Jul 20;20(4):881-885. doi: 10.33314/jnhrc.v20i4.4233.

ABSTRACT

BACKGROUND: Cutaneous warts are common skin problems caused by Human Papilloma Virus. Conventional therapies are mostly ablative and limited by recurrences and side effects. Immunotherapy using bacterial, fungal, and viral antigens is an emerging and safer technique to treat warts at local and distant sites. The objective of this study was to measure the efficacy and safety of intralesional immunotherapy with tuberculin purified protein derivative among cutaneous wart patients in the dermatology department of a tertiary care centre.

METHODS: A cross sectional, time series design, was conducted between October 2019 and September 2020 among 77 patients of cutaneous warts attending Dermatology out-patient department using convenience sampling. Percentage response was evaluated for patients treated with tuberculin purified protein derivative for eight weeks at an interval of two weeks into complete response (100% clearance), partial response (50-99% clearance), no response (0-49% clearance). Side effects were also recorded. Statistical Package for the Social Sciences version 20.0 was used for data analysis.

RESULTS: Out of 77 patients, complete response (100%) was seen in 53.2% patients, partial response (50-99%) in 14.3% and no response (0-49%) was seen in 32.5%. Side effects noted were pain and erythema (19.50%), blisters (2.60%) and flu like symptoms (1.30%).

CONCLUSIONS: Intralesional PPD is an effective and safer therapeutic option for the treatment of cutaneous warts.

PMID:37489671 | DOI:10.33314/jnhrc.v20i4.4233

Int J Nanomedicine. 2023 Jul 19;18:3913-3935. doi: 10.2147/IJN.S417855. eCollection 2023.

ABSTRACT

Anesthetics, which include both local and general varieties, are a unique class of drugs widely utilized in clinical surgery to alleviate pain and promote relaxation in patients. Although numerous anesthetics and their traditional formulations are available in the market, only a select few exhibit excellent anesthetic properties that meet clinical requirements. The main challenges are the potential toxic and adverse effects of anesthetics, as well as the presence of the blood-brain barrier (BBB), which makes it difficult for most general anesthetics to effectively penetrate to the brain. Loading anesthetics onto nanocarriers as anesthetic nanomedicines might address these challenges and improve anesthesia effectiveness, reduce toxic and adverse effects, while significantly enhance the efficiency of general anesthetics passing through the BBB. Consequently, anesthetic nanomedicines play a crucial role in the field of anesthesia. Despite their significance, research on anesthetic nanomedicines is still in its infancy, especially when compared to other types of nanomedicines in terms of depth and breadth. Although local anesthetic nanomedicines have received considerable attention and essentially meet clinical needs, there are few reported instances of nanomedicines for general anesthetics. Given the extensive usage of anesthetics and the many of them need for improved performance, emerging anesthetic nanomedicines face both unparalleled opportunities and considerable challenges in terms of theory and technology. Thus, a comprehensive summary with systematic analyses of anesthetic nanomedicines is urgently required. This review provides a comprehensive summary of the classification, properties, and research status of anesthetic nanomedicines, along with an exploration of their opportunities and challenges. In addition, future research directions and development prospects are discussed. It is hoped that researchers from diverse disciplines will collaborate to study anesthetic nanomedicines and develop them as a valuable anesthetic dosage form for clinical surgery.

PMID:37489141 | PMC:PMC10363368 | DOI:10.2147/IJN.S417855

Yonsei Med J. 2023 Aug;64(8):511-517. doi: 10.3349/ymj.2023.0124.

ABSTRACT

PURPOSE: Anatomical landmarks can provide vital information on the distribution of nerves in the gastrocnemius muscle. We aimed to provide an anatomical perspective on appropriate locations for botulinum neurotoxin (BoNT) injections in the medial and lateral parts of the gastrocnemius for calf shaping.

MATERIALS AND METHODS: A modified Sihler's method was applied to both the medial and lateral parts of the gastrocnemius muscles (16 specimens). Intramuscular neural distributions were revealed by dissecting along a transverse line crossing the fibular head and superior margin of the calcaneal tuberosity.

RESULTS: The intramuscular neural distribution for the medial and lateral parts of the gastrocnemius had the greatest arborized patterns in the 7/10-8/10 section of the medial head and 7.5/10-8.5/10 section of the lateral part of the gastrocnemius.

CONCLUSION: We propose that BoNT injections should be directed to the 7/10-8/10 section of the medial head and the 7.5/10-8.5/10 section of the lateral part of the gastrocnemius. Following our guidelines, clinicians can ensure satisfactory results with the use of minimal doses to limit adverse effects, such as gait disturbance, antibody production, and bruising, due to multiple injections. The results can also be altered and applied to electromyography.

PMID:37488703 | DOI:10.3349/ymj.2023.0124

Z Rheumatol. 2023 Jul 25. doi: 10.1007/s00393-023-01390-x. Online ahead of print.

ABSTRACT

Modulation of the parasympathetic tone leads to extensive physiological reactions at several levels, including the decreased production of proinflammatory cytokines. Many studies have demonstrated that chronic inflammatory diseases are associated with reduced parasympathetic and increased sympathetic activities. Moreover, it was demonstrated that a low parasympathetic and a high sympathetic activity in patients with rheumatoid arthritis (RA) predicts a poor therapeutic response to anti-tumor necrosis factor (TNF) treatment compared to RA patients with a more balanced autonomic nervous system. The autonomic equilibrium could be restored by electrical stimulation of the vagus nerve. Considering the patients who do not sufficiently respond to the available drugs, patients for whom the effectiveness of the drugs wanes over time, or have drug-related adverse events, a nonpharmacological approach such as bioelectronics might be a useful supplement as an instrument in the successful extension of the therapeutic armamentarium for rheumatic diseases; however, there is a great need for further studies and the development of novel therapeutic strategies in the field of neuroimmunology.

PMID:37490129 | DOI:10.1007/s00393-023-01390-x

Cureus. 2023 Jun 23;15(6):e40842. doi: 10.7759/cureus.40842. eCollection 2023 Jun.

ABSTRACT

Metoclopramide hydrochloride is a widely used medication for the treatment of gastrointestinal disorders such as nausea, vomiting, and gastroparesis. However, it has been associated with extrapyramidal side effects (EPS) such as tardive dyskinesia, nystagmus, and other locomotive disorders on rare occasions. These reactions are commonly seen in children and females, particularly in young people. In this article, we report a rare case of a 15-week pregnant woman who was prescribed metoclopramide hydrochloride in view of nausea and vomiting, which was later diagnosed as vomiting in pregnancy not relieved with first-line medications, and has later developed drug-induced nystagmus, highlighting its unpredictable nature and shortcomings of management in the pregnant woman. This article will draw the attention of obstetricians and gynecologists to wisely prescribe metoclopramide hydrochloride for treating nausea and vomiting in pregnant women.

PMID:37489191 | PMC:PMC10363280 | DOI:10.7759/cureus.40842