Circ Genom Precis Med. 2022 May 11:101161CIRCGEN121003503. doi: 10.1161/CIRCGEN.121.003503. Online ahead of print.

ABSTRACT

BACKGROUND: Statin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the p.Val174Ala missense variant in SLCO1B1 and SAMS in simvastatin-treated subjects; however, evidence for genetic predictors of SAMS in atorvastatin- or rosuvastatin-treated subjects is currently lacking.

METHODS: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; n=18 924) was a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of alirocumab (a PCSK9 [proprotein convertase subtilisin kexin 9] inhibitor) in acute coronary syndrome patients receiving high-intensity statin therapy. The goal of this pharmacogenomic analysis was to identify genetic variants associated with atorvastatin- and rosuvastatin-mediated SAMS among ODYSSEY OUTCOMES subjects who consented to participate in the genetic study (n=11 880). We performed multi-ancestry exome-wide and genome-wide association studies and gene burden analysis across 2 phenotypes (clinical SAMS [n=10 617] and creatine kinase [n=9630] levels).

RESULTS: A novel genome-wide significant association for an intronic variant (rs6667912) located within TMEM9 (odds ratio [95% CI], 1.39 [1.24-1.55]; P=3.71×10-8) for patients with clinical SAMS (cases=894, controls=9723) was identified. This variant is located ≈30 kb upstream of CACNA1S, a locus associated with severe SAMS. We replicated 2 loci, at LINC0093 and LILRB5, previously associated with creatine kinase levels during statin treatment. No association was observed between p.Val174Ala (rs4149056) in SLCO1B1 and SAMS (odds ratio [95% CI], 1.03 [0.90-1.18]; P=0.69).

CONCLUSIONS: This study comprises the largest discovery exome-wide and genome-wide association studies for atorvastatin- or rosuvastatin-mediated SAMS to date. These novel genetic findings may provide biological/mechanistic insight into this drug-induced toxicity, and help identify at-risk patients before selection of lipid-lowering therapies.

PMID:35543701 | DOI:10.1161/CIRCGEN.121.003503

QJM. 2022 May 10;115(5):267. doi: 10.1093/qjmed/hcac106.

NO ABSTRACT

PMID:35535603 | DOI:10.1093/qjmed/hcac106

Evid Based Complement Alternat Med. 2022 Apr 30;2022:4777849. doi: 10.1155/2022/4777849. eCollection 2022.

ABSTRACT

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, is characterized by various clinical symptoms and reduced quality of life. The standard dopaminergic therapy for PD has limitations such as drug wear-off, drug-related side effects, and drug-resistant PD symptoms. Traditional oriental medicine, which is a personalized approach based on pattern identification (PI), has been reported to relieve symptoms, halt disease progression, and improve the quality of life in patients with PD. This comprehensive systematic review will be conducted to gather clinical studies related to complementary traditional herbal therapies based on PI for idiopathic PD and assess its effectiveness. Clinical studies, including randomized controlled trials in English, Korean, and Chinese databases related to the efficacy of herbal medicine based on PI for PD will be searched in computer retrieval. In addition, the subdivided PI for each clinical manifestation of PD will be investigated. Two researchers will independently screen and select studies, extract data, and assess bias risk. The risk of bias will be evaluated using the Cochrane risk-of-bias assessment tool. After screening the studies, a meta-analysis will be performed. The primary outcome will be the unified Parkinson's disease rating scale to measure clinical symptom reduction. Secondary outcomes will consist of other validated scales to evaluate the improvement of PD, including improvement of clinical symptoms and quality of life. The quality of evidence will be evaluated through the Grading of Recommendations, Assessment, Development, and Evaluation pro. Complementary traditional medicine is a personalized medicine that classifies individual states based on PI. We expect that the results of this review will provide evidence for the efficacy of traditional herbal medicine based on PI for the treatment of PD. This protocol has been registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) 2021 (registration number INPLASY2021100020).

PMID:35535156 | PMC:PMC9078772 | DOI:10.1155/2022/4777849

Skinmed. 2022 Apr 30;20(2):126-129. eCollection 2022.

ABSTRACT

Adverse reactions to drugs are a major concern in health, and children seem to be particularly vulnerable to these reactions. Cutaneous reactions account for 35% of the drug-related adverse effects in children. We conducted a retrospective study to characterize the pediatric population having a diagnosis of cutaneous adverse drug reactions (CADRs) in children admitted in a tertiary hospital during 6 years. (SKINmed. 2022;20:126-129).

PMID:35532765

Reg Anesth Pain Med. 2022 May 9:rapm-2021-103461. doi: 10.1136/rapm-2021-103461. Online ahead of print.

ABSTRACT

Neuraxial opioids are well known to cause itching, which may be challenging to treat. Neuraxial morphine has been demonstrated to cause recrudescent herpes simplex viruses (HSV-1), especially in women during labor and childbirth with neuraxial analgesia, and may be an occult etiology of refractory itching. This educational review summaries the clinical and epidemiological characteristics associated with recrudescent HSV-1 in patients treated with neuraxial opioids, especially morphine.

PMID:35534019 | DOI:10.1136/rapm-2021-103461

Eur J Paediatr Neurol. 2022 Apr 30;39:1-10. doi: 10.1016/j.ejpn.2022.04.006. Online ahead of print.

ABSTRACT

OBJECTIVES: This systematic review aimed to assess mid- and long-term (at least 12 months) real-world study data from all types of spinal muscular atrophy (SMA) patients treated with any of the approved drugs or combination therapies.

METHODS: A systematic literature search was carried out in five databases. Two authors selected the studies based on pre-defined selection criteria and independently graded the risk of bias at study level.

RESULTS: Five hundred forty-six records were identified in the literature search and 22 studies (in 26 publications) were included in the analysis. Nusinersen, onasemnogene abeparvovec and combination therapies improved motor endpoints in SMA type 1 patients. SMA type 2 to type 4 patients treated with nusinersen showed stabilisation or small improvements in motor endpoints with some deterioration observed. Quality of life endpoints, such as respiratory and nutritional support were poorly reported on. Drug-related adverse events occurred rarely in all types of SMA patients with all assessed drugs. Mid- and long-term studies on risdiplam could not be identified.

CONCLUSIONS: The large quantity of missing data and heterogeneity of studies hinder comparability. Although stability and further improvement on the long-term is still uncertain, the results from the included evidence, as well as from pivotal trials show a striking contrast to the natural progression of the disease.

PMID:35533607 | DOI:10.1016/j.ejpn.2022.04.006

Neurol India. 2022 Mar-Apr;70(2):633-637. doi: 10.4103/0028-3886.344646.

ABSTRACT

BACKGROUND: Dopamine deficiency causes Parkinson's disease (PD), and on treatment, levodopa is the gold standard. Various drug-metabolizing enzymes and drug receptors are believed to be involved in prompting dyskinesias due to the extended usage of levodopa. Shreds of evidence in genomic studies have presented that ADORA2A receptor antagonism has beneficial outcomes to avoid these drug-induced side effects.

OBJECTIVE: The aim of this study was to study the polymorphisms of rs2298383, rs35060421, and rs5751876 in the ADORA2A in patients diagnosed as PD and describe their possible relationships with levodopa-induced dyskinesias (LID).

METHODS: One-hundred and seventy-two patients were recruited and separated as the study and the control group. DNA was achieved from peripheral venous blood, high resolution melting analysis, and reverse-transcriptase PCR was performed.

RESULTS: The allele differences among the groups were not statistically significant. Although it was not statistically significant, the rs35060421 allele was observed to repeat more frequently. However, we did not find an association between such polymorphisms of ADORA2A and LID.

CONCLUSIONS: Although this result showed that a higher sample number might produce different results as possible, current results in the Turkish sample indicated that these alleles of ADORA2A might not be related to LID in patients.

PMID:35532631 | DOI:10.4103/0028-3886.344646

Int J Pharm Pract. 2022 May 9:riac037. doi: 10.1093/ijpp/riac037. Online ahead of print.

ABSTRACT

BACKGROUND: Paediatric patients are at high risk of medication errors and adverse drug events due to complex medical care.

OBJECTIVE: To assess the impact of pharmacist medication review for paediatric patients.

SETTING: A single-centre prospective observational study was performed over 33 months, from February 2018 to October 2020 in a French Hospital.

METHOD: Clinical pharmacists provided medication counselling at a hospital and conducted telephone follow-ups between 3 and 7 days after discharge of paediatric patients with chronic diseases for whom treatment was introduced or modified during hospitalisation or hospital consultations.

MAIN OUTCOME MEASURES: The incidence of drug-related problems (DRPs), the number and type of pharmacist intervention and paediatrician acceptance rates were assessed. Parents' understanding and drug-related needs were compared before and after medication review. Time to outpatient treatment and patient satisfaction were determined. Statistical analyses were performed in Excel.

RESULTS: In total, 195 paediatric patients were included. Pharmacists identified 65 interventions, 95% of which were accepted. The most frequent DRPs included inappropriate drug administration (32.3%), herb-drug interactions (24.6%) and dose selection (17%). Parents' knowledge increased by 28% from baseline after pharmacist's medication counselling. Parents' drug-related needs concerning administration and side effects decreased by 67% and 49%, respectively, following the pharmacist's medication counselling. Most (75%) of the patients were able to get their treatment immediately after discharge.

CONCLUSION: Clinical pharmacists can improve medication safety for children during the discharge process or consultations, by reducing prescription errors, optimising administration, counselling patients or parents and helping to ensure care continuity.

PMID:35532336 | DOI:10.1093/ijpp/riac037

HIV Med. 2022 May 8. doi: 10.1111/hiv.13319. Online ahead of print.

ABSTRACT

OBJECTIVES: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study.

METHODS: In this 96-week, phase 3b, open-label, single-arm trial, virologically suppressed PLWH aged ≥65 years switched from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen to B/F/TAF. Viral suppression, resistance, immune response, safety, tolerability and adherence were evaluated through week 96.

RESULTS: Of 90 participants screened, 86 were enrolled and switched to B/F/TAF. No participants had HIV-1 RNA ≥50 copies/ml (by FDA Snapshot algorithm) at weeks 72 or 96; virologic suppression rates were 94.2% (81/86; 95% CI 87.0-98.1) and 74.4% (64/86; 95% CI 63.9-83.2), respectively. No treatment-emergent resistance was observed, and CD4 counts remained stable. There were no study drug-related serious adverse events. Three participants experienced drug-related treatment-emergent adverse events that led to premature drug discontinuation. There were no clinically relevant changes from baseline to week 96 in fasting lipid parameters, and the median change in body weight at week 96 was 0.0 kg (IQR -2.3, 2.0). Median self-reported adherence was 100% (IQR 100-100%).

CONCLUSIONS: Switching to B/F/TAF is an effective long-term option for virologically suppressed adults ≥65 years of age, with favourable safety and tolerability profiles in this population.

PMID:35527425 | DOI:10.1111/hiv.13319

Cogn Res Princ Implic. 2022 May 7;7(1):38. doi: 10.1186/s41235-022-00387-5.

ABSTRACT

On April 13, 2021, the CDC announced that the administration of Johnson and Johnson's COVID-19 vaccine would be paused due to a rare blood clotting side effect in ~ 0.0001% of people given the vaccine. Most people who are hesitant to get a COVID-19 vaccine list potential side effects as their main concern (PEW, 2021); thus, it is likely that this announcement increased vaccine hesitancy among the American public. Two days after the CDC's announcement, we administered a survey to a group of 2,046 Americans to assess their changes in attitudes toward COVID-19 vaccines. The aim of this study was to investigate whether viewing icon arrays of side effect risk would prevent increases in COVID-19 vaccine hesitancy due to the announcement. We found that using icon arrays to illustrate the small chance of experiencing the blood clotting side effect significantly prevented increases in aversion toward the Johnson and Johnson vaccine as well as all other COVID-19 vaccines.

PMID:35524896 | PMC:PMC9077983 | DOI:10.1186/s41235-022-00387-5

J Med Case Rep. 2022 May 7;16(1):182. doi: 10.1186/s13256-022-03407-6.

ABSTRACT

BACKGROUND: Many scientists across the world got involved in the race to develop successful anti-SARS-CoV-2 vaccines to overcome COVID-19 pandemic. Among the different vaccines developed against SARS-CoV-2, Covishield was the first vaccine approved for emergency use in Nepal. We report two cases of Superficial Vein Thrombosis (SVT) for the first time in the literature after vaccination with the Chimpanzee Adenovirus-vectored Vaccine (ChAdOx1 nCoV-19 vaccine).

CASES PRESENTATION: Two cases, a 24-year-old young Chhetri male and a 62-year-old Chhetri female who have received Covishield (ChAdOx1 nCoV-19) vaccine, developed pain in left calf after 2 weeks and 10 weeks of vaccination, respectively. Both the case belongs to the Chhetri ethnic group of Nepal. The pain became severe on the fourth week of immunization in the first case while the pain was acute and severe on the 10th week of vaccination in the second case. The first presented to emergency room and second case was referred to the emergency room from Orthopedic Clinic. On evaluation the first patient had normal vitals with no history of fever and swelling yet displayed non-radiating mild to moderate intensity pain localized to left leg below the knee which became aggravated by movements. In the second case however pain was more intense with other characteristics as first case. Both cases had low wells score (< 4). On local examination tenderness was noted on squeezing but other systemic examination findings of the patient were within normal limits in both cases. Among the numerous vaccines used to fight the battle against COVID-19 disease, the ChAdOx1 nCoV-19 vaccine, Covishield, has been widely used in Nepal and India. Apart from other minor side effects, in few cases thromboses have been reported after vaccination of ChAdOx1 nCoV-19, Covishield, vaccine.

CONCLUSION: These cases reporting Superficial Vein Thrombosis may be an additional adverse effect to the list of adverse events associated with ChAdOx1 nCoV-19, Covishield, vaccine. However, the benefits of the vaccine in breaking the chain of COVID 19 spread are certainly greater than the risk of thromboses.

PMID:35524323 | PMC:PMC9076162 | DOI:10.1186/s13256-022-03407-6

Fam Med Community Health. 2022 May;10(2):e001541. doi: 10.1136/fmch-2021-001541.

ABSTRACT

OBJECTIVE: Understanding the side effects and acceptability of thermal ablation (TA) is necessary before large-scale application in screen-and-treat programmes can be justified in low-income and middle-income countries (LMICs).

DESIGN: Articles were selected for inclusion by two independent reviewers. Risk of bias was assessed using the Downs and Black's criteria. Summary data were extracted, and authors contacted for data when necessary. Proportions of interest and 95% CIs were estimated using a random effects model. Subgroup analysis was performed based on place of treatment and timing of post-treatment follow-up. Heterogeneity was estimated using the I2.

ELIGIBILITY CRITERIA: Studies that reported one or more side effects or patient acceptability measures after treatment of the cervix using TA in women living in LMICs who completed a cervical cancer screening test. Included articles were clinical trials or observational studies available in English and published before 18 December 2020.

INFORMATION SOURCES: Ovid MEDLINE, EMBASE, CINAHL, CAB Global Health and WHO Global Index Medicus were searched for this systematic review and meta-synthesis.

RESULTS: A total of 1590 abstracts were screened, 84 full text papers reviewed and 15 papers selected for inclusion in the qualitative review, 10 for meta-synthesis (N=2039). Significant heterogeneity was found in screening tests used to identify women eligible for TA and in methods to ascertain side effects. The most commonly reported side effect during treatment was pain (70%, 95% CI 52% to 85%; I2=98.01%) (8 studies; n=1454). No women discontinued treatment due to pain. At treatment follow-up, common side effects included vaginal discharge (72%, 95% CI 18% to 100%; I2=99.55%) (5 studies; n=771) and bleeding (38%, 95% CI 15% to 64%; I2=98.14%) (4 studies; n=856). Satisfaction with treatment was high in 99% (95% CI 98% to 100%; I2=0.00%) of women (3 studies; n=679).

CONCLUSIONS: TA results in a number of common side effects, though acceptability remains high among women treated in LMICs. Standardised side effect and acceptability reporting are needed as TA becomes more readily available.

PROSPERO REGISTRATION NUMBER: CRD42020197605.

PMID:35523456 | DOI:10.1136/fmch-2021-001541

Eur J Hosp Pharm. 2022 May 6:ejhpharm-2022-003237. doi: 10.1136/ejhpharm-2022-003237. Online ahead of print.

ABSTRACT

OBJECTIVES: This study analysed whether the Model List of Essential Medicines is suitable for elderly patients. Furthermore, it investigated the specific issues that should be considered when prescribing a drug and which drugs should be added to improve the list according to the explicit criteria guidelines.

METHODS: A qualitative descriptive review was performed comparing the explicit criteria guidelines of Beers 2019, Laroche, McLeod, NORGEP, PRISCUS, STOPP/START 2014 and Winit-Watjana with the 22nd edition of the Model List of Essential Medicines.

RESULTS: The Model List of Essential Medicines has 458 drugs. Depending on the explicit criteria considered, there were different numbers of potentially inappropriate medications and potential prescribing omissions. When all explicit criteria were combined, a total of 73 medicines were classified as potentially inappropriate. Using the STOPP/START criteria, 46 potential prescribing omissions were detected. According to these explicit criteria, the Model List of Essential Medicines appeared to lack some medicines.

CONCLUSIONS: Explicit criteria guidelines have different potential for detecting potentially inappropriate medications. Our findings suggest that some drugs should be added to the next edition of the Model List of Essential Medicines to cover some therapeutic gaps.

PMID:35523536 | DOI:10.1136/ejhpharm-2022-003237

Front Pharmacol. 2022 Apr 20;13:676831. doi: 10.3389/fphar.2022.676831. eCollection 2022.

ABSTRACT

Introduction: Extensive use of antiretroviral therapy has remarkably improved the survival rates of people living with HIV. Doravirine (DOR) is a newly-approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors. Here, we compared the efficacy and safety of DOR + tenofovir dipivoxil fumarate (TDF)+Lamivudine (3TC)/Emtritabine (FTC) with traditional triple therapies in treatment-naïve HIV-1-positive adults. Methods: Randomized controlled trials involving treatment-naïve HIV-1-positive adults that met inclusion criteria were systematically retrieved and data on the following outcomes extracted: virological suppression, adverse events, severe adverse events, and drug-related adverse events. A Bayesian network meta-analysis was then performed on the data. Results: This study included a total of 39 randomized controlled trials involving 26 antiretroviral therapies and 21,110 HIV1-positive patients. At week 48, relative to the other 25 regimens included in the network of virological suppression, DOR + TDF+3TC/FTC exhibited superiority to some efavirenz, nevirapine, atazanavir, or lopinavir-based regimens, including efavirenz + abacavir+3TC [Odd Ratio (OR) = 0.52, 95% confidence interval (CrI) = 0.35-0.77]. At week 48, the performance of DOR + TDF+3TC/FTC was relatively similar to all other analyzed regimens in terms of adverse events. The DOR + TDF+3TC/FTC regimen performed better in terms of severe adverse events and drug-related adverse events. Conclusion: The network meta-analysis showed that DOR + TDF+3TC/FTC has good efficacy and safety at 48 weeks. Systematic Review Registration: Open Science Framework, https://osf.io/6ybp7.

PMID:35517782 | PMC:PMC9065253 | DOI:10.3389/fphar.2022.676831

Pulm Circ. 2022 Apr 7;12(2):e12063. doi: 10.1002/pul2.12063. eCollection 2022 Apr.

ABSTRACT

Inhaled treprostinil is an approved therapy for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease in the United States. Studies have confirmed the robust benefits and safety of nebulized inhaled treprostinil, but it requires a time investment for nebulizer preparation, maintenance, and treatment. A small, portable treprostinil dry powder inhaler has been developed for the treatment of PAH. The primary objective of this study was to evaluate the safety and tolerability of treprostinil inhalation powder (TreT) in patients currently treated with treprostinil inhalation solution. Fifty-one patients on a stable dose of treprostinil inhalation solution enrolled and transitioned to TreT at a corresponding dose. Six-minute walk distance (6MWD), device preference and satisfaction (Preference Questionnaire for Inhaled Treprostinil Devices [PQ-ITD]), PAH Symptoms and Impact (PAH-SYMPACT®) questionnaire, and systemic exposure and pharmacokinetics for up to 5 h were assessed at baseline for treprostinil inhalation solution and at Week 3 for TreT. Adverse events (AEs) were consistent with studies of inhaled treprostinil in patients with PAH, and there were no study drug-related serious AEs. Statistically significant improvements occurred in 6MWD, PQ-ITD, and PAH-SYMPACT. Forty-nine patients completed the 3-week treatment phase and all elected to participate in an optional extension phase. These results demonstrate that, in patients with PAH, transition from treprostinil inhalation solution to TreT is safe, well-tolerated, and accompanied by statistically significant improvements in key clinical assessments and patient-reported outcomes with comparable systemic exposure between the two formulations at evaluated doses (trial registration: clinicaltrials.gov identifier: NCT03950739).

PMID:35514770 | PMC:PMC9063953 | DOI:10.1002/pul2.12063

Pharmacol Biochem Behav. 2022 May 2:173394. doi: 10.1016/j.pbb.2022.173394. Online ahead of print.

ABSTRACT

Kappa-opioid receptor (KOR) agonists have been studied as potential treatments for pain, pruritus, and substance-use disorders, but prototypical KOR agonists produce side-effects like dysphoria and sedation. Atypical KOR agonists that exhibit G-protein biased signaling at the KOR have been reported to produce therapeutic-like effects with fewer or reduced side-effects relative to prototypical KOR agonists. In the current report, behavioral profiles were determined using a behavioral scoring system that was modified to quantify drug-induced behaviors in nonhuman primates (NHPs). Profiles were determined for a prototypical and two biased KOR agonists, alone and combined with the mu-opioid receptor (MOR) agonist, oxycodone. Five adult male rhesus monkeys implanted with intravenous catheters were administered a range of doses of the KOR agonist, U50-488H (0.01-0.1 mg/kg) and the biased KOR agonists, nalfurafine (0.0001-0.001 mg/kg) and triazole 1.1 (0.32-1.0 mg/kg), alone and combined with the MOR agonist, oxycodone (0.01-0.32 mg/kg). In addition, the largest triazole 1.1 dose tested (1.0 mg/kg) was administered in time-course determinations (0-56 min), alone and combined with oxycodone (0.1 mg/kg). U50-488H and nalfurafine produced sedative-like and motor-impairing effects. Triazole 1.1 had a milder side-effect profile, in some instances producing sedative-like effects but to a lesser degree compared with the other KOR agonists, particularly for lip droop and rest/sleep posture. All KOR agonists reduced oxycodone-induced scratch, but nalfurafine produced behavior-disrupting and sedative-like effects when combined with oxycodone that were not observed with triazole 1.1. The duration of triazole 1.1's behavioral effects was relatively short, dissipating entirely by 56 min. Our results suggest that KOR agonists with comparable pharmacology to triazole 1.1 may be useful therapeutics with reduced side-effect profiles, and the mechanisms conferring these benefits may be attributed to factors other than G-protein bias.

PMID:35513117 | DOI:10.1016/j.pbb.2022.173394

J Pharmacol Sci. 2022 Jun;149(2):60-65. doi: 10.1016/j.jphs.2022.03.004. Epub 2022 Mar 26.

ABSTRACT

Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35-150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1-85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.

PMID:35512856 | DOI:10.1016/j.jphs.2022.03.004

Cureus. 2022 Mar 29;14(3):e23635. doi: 10.7759/cureus.23635. eCollection 2022 Mar.

ABSTRACT

New-onset diabetes mellitus (NODM) is a common long-term complication after liver transplantation (LT). It is thought to be drug-induced in most cases, no matter the underlying disease that cause liver failure and indicated transplantation. Standard post-transplantation (PT) immunosuppressive regimens include prolonged use of calcineurin inhibitors (CNIs), namely tacrolimus (TAC), alongside corticosteroids to avoid acute and chronic graft rejection. This combination is well known for its diabetogenicity. Significant differences between the applied regimens stand out concerning the duration and dosages to prevent the metabolic side effects of these drugs in the long run without compromising the graft's survival. Studies were collected after an extensive research of PubMed database for this very specific topic using the following MeSH keywords in multiple combinations: "Liver Transplantation," "Diabetes Mellitus," "NODM," "Tacrolimus," "Cyclosporine A," and "Steroids." In addition, we used the same keywords for regular searches in Google Scholar. Only the relevant English human studies between 2010 and 2020 were collected except for review articles. Duplicates were eliminated using Mendeley software. Twelve relevant studies directly related to the targeted topic were collected and discussed, including five retrospective cohorts, four prospective cohorts, one clinical trial, one prospective pilot, and one case report. Their topics included primarily the factors increasing the risk of new-onset diabetes mellitus after liver transplantation (NODALT), TAC-based immunosuppression and its relative blood levels affecting the possible development of NODALT, the role of cyclosporine in substituting TAC regimen, and the effect of different steroids-avoiding protocols on the prevention of NODALT. The reviewed studies suggested that lowering the serum concentration of tacrolimus (cTAC) throughout the PT period and eliminating the corticosteroids regimen as early as possible, among other measures, can significantly impact the rate of emergence of NODM. This traditional review tackles the most recent studies about NODALT to establish a comprehensive view on this issue and guide clinicians and researchers for the safest immunosuppressive regimen to date, while maintaining a balanced metabolic profile.

PMID:35510006 | PMC:PMC9057316 | DOI:10.7759/cureus.23635

Cureus. 2022 Mar 31;14(3):e23693. doi: 10.7759/cureus.23693. eCollection 2022 Mar.

ABSTRACT

Drug-induced nephrotoxicity and neurotoxicity are commonly encountered problems in clinical practice. We describe a case of concurrent valacyclovir-induced nephrotoxicity and neurotoxicity in a 64-year-old man with no history of renal disease who developed acute renal injury and neurological symptoms after he received two weeks of the standard dose of oral valacyclovir for herpes zoster meningitis. His clinical condition improved significantly after the initiation of hemodialysis. Although nephrotoxicity due to intravenous infusion of valacyclovir and/or acyclovir is not uncommon, oral valacyclovir therapy is rarely associated with nephrotoxicity in patients with no history of renal insufficiency. Additionally, concurrent nephrotoxicity and neurotoxicity due to valacyclovir and/or acyclovir are rarely reported. Clinicians should be aware of these adverse events as immediate recognition and intervention are necessary to prevent morbidity.

PMID:35509998 | PMC:PMC9060728 | DOI:10.7759/cureus.23693

PLoS One. 2022 May 4;17(5):e0267901. doi: 10.1371/journal.pone.0267901. eCollection 2022.

ABSTRACT

Early detection and management of adverse drug reactions (ADRs) is crucial for improving patients' quality of life. Hand-foot syndrome (HFS) is one of the most problematic ADRs for cancer patients. Recently, an increasing number of patients post their daily experiences to internet community, for example in blogs, where potential ADR signals not captured through routine clinic visits can be described. Therefore, this study aimed to identify patients with potential ADRs, focusing on HFS, from internet blogs by using natural language processing (NLP) deep-learning methods. From 10,646 blog posts, written in Japanese by cancer patients, 149 HFS-positive sentences were extracted after pre-processing, annotation and scrutiny by a certified oncology pharmacist. The HFS-positive sentences described not only HFS typical expressions like "pain" or "spoon nail", but also patient-derived unique expressions like onomatopoeic ones. The dataset was divided at a 4 to 1 ratio and used to train and evaluate three NLP deep-learning models: long short-term memory (LSTM), bidirectional LSTM and bidirectional encoder representations from transformers (BERT). The BERT model gave the best performance with precision 0.63, recall 0.82 and f1 score 0.71 in the HFS user identification task. Our results demonstrate that this NLP deep-learning model can successfully identify patients with potential HFS from blog posts, where patients' real wordings on symptoms or impacts on their daily lives are described. Thus, it should be feasible to utilize patient-generated text data to improve ADR management for individual patients.

PMID:35507636 | DOI:10.1371/journal.pone.0267901