Adv Pharmacol. 2022;95:49-72. doi: 10.1016/bs.apha.2022.05.001. Epub 2022 Jul 20.

ABSTRACT

With the availability of detailed genomic data on all 57 human cytochrome P450 genes, it is clear that there is substantial variability in gene product activity with functionally significant polymorphisms reported across almost all isoforms. This article is concerned mainly with 13 P450 isoforms of particular relevance to xenobiotic metabolism. After brief review of the extent of polymorphism in each, the relevance of selected P450 isoforms to both adverse drug reaction and disease susceptibility is considered in detail. Bleeding due to warfarin and other coumarin anticoagulants is considered as an example of a type A reaction with idiosyncratic adverse drug reactions affecting the liver and skin as type B. It is clear that CYP2C9 variants contribute significantly to warfarin dose requirement and also risk of bleeding, with a minor contribution from CYP4F2. In the case of idiosyncratic adverse drug reactions, CYP2B6 variants appear relevant to both liver and skin reactions to several drugs with CYP2C9 variants also relevant to phenytoin-related skin rash. The relevance of P450 genotype to disease susceptibility is also considered but detailed genetic studies now suggest that CYP2A6 is the only P450 relevant to risk of lung cancer with alleles associated with low or absent activity clearly protective against disease. Other cytochrome P450 genotypes are generally not predictors for risk of cancer or other complex disease development.

PMID:35953163 | DOI:10.1016/bs.apha.2022.05.001

Adv Pharmacol. 2022;95:1-47. doi: 10.1016/bs.apha.2021.12.001. Epub 2022 Jul 18.

ABSTRACT

The development of the cytochrome P450 (P450) field has been remarkable in the areas of pharmacology and toxicology, particularly in drug development. Today it is possible to use the knowledge base and relatively straightforward assays to make intelligent predictions about drug disposition prior to human dosing. Much is known about the structures, regulation, chemistry of catalysis, and the substrate and inhibitor specificity of human P450s. Many aspects of drug-drug interactions and side effects can be understood in terms of P450s. This knowledge has also been useful in pharmacy practice, as well as in the pharmaceutical industry and medical practice. However, there are still basic and practical questions to address regarding P450s and their roles in pharmacology and toxicology. Another aspect is the discovery of drugs that inhibit P450 to treat diseases.

PMID:35953152 | DOI:10.1016/bs.apha.2021.12.001

Clin Rheumatol. 2022 Aug 11. doi: 10.1007/s10067-022-06327-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Intra-articular corticosteroid injection (IACI) is generally used in the management of juvenile idiopathic arthritis (JIA) to obtain rapid relief of active synovitis and functional recovery and to prevent the need for regular systemic therapy. The aim of this study was to investigate the outcome of IACI treatment and the factors associated with remission of synovitis.

METHODS: The clinical records of JIA patients who received IACI between January 2014 and December 2020 in two pediatric rheumatology centers were reviewed. The procedure was evaluated in terms of efficacy, factors that may affect the duration of remission, procedural and drug-related complications.

RESULTS: During the study period, 134 patients received 227 injections and 37 joints were injected more than once. One hundred and six (79%) patients had persistent oligoarticular disease. At the time of injection, all patients were receiving non-steroidal anti-inflammatory drugs, 74 patients were on methotrexate, and 14 patients were on biologics. The median duration of remission without exacerbation of synovitis treated with IACI was 15 (range 1-64) months. The inactivity rate was 81% at the 6th month after the injection. It has been shown that being less than 7 years old at disease onset and low initial CRP levels were correlated with a long remission period (p < 0.05). Despite the differences were not statistically significant, the duration of remission was longer in boys, in ANA positives, in HLA-B27 negatives, in patients with concurrent methotrexate treatment and in patients not receiving biologic therapy (p > 0.05). Only two patients (1.5%, 95% CI - 0.6 to 3.5) developed cutaneous hypopigmentation and subcutaneous atrophy as side effects of injection.

CONCLUSION: Intra-articular corticosteroid injection was more effective especially in patients with low initial CRP levels and younger than 7 years of age. The duration of remission was longer in these patients. Key Points • Intra-articular corticosteroid injection is an effective method for controlling joint inflammation and achieving long-term remission without significant side effects. • Intra-articular corticosteroid injection can be preferred in all forms of juvenile idiopathic arthritis as primary therapy or to relieve the patient while waiting for the effect of systemic agents or to avoid increasing the dose of systemic drugs. • It can be recommended as a treatment option at any stage of the disease, especially in young patients and patients with low initial CRP values.

PMID:35953685 | DOI:10.1007/s10067-022-06327-4

HPB (Oxford). 2022 Jul 21:S1365-182X(22)01536-2. doi: 10.1016/j.hpb.2022.07.011. Online ahead of print.

ABSTRACT

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a significant contributor to morbidity after pancreatectomy. Somatostatin analogues have shown variable efficacy in the prevention of CR-POPF. Lanreotide is a somatostatin analogue ideally suited for perioperative use due to its long half-life and favorable side effect profile.

METHODS: We conducted a phase II single-arm trial of a single dose of preoperative lanreotide (120 mg) in patients undergoing either pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). The primary outcome was development of CR-POPF or intra-abdominal abscess. Secondary outcomes included biochemical leak and overall morbidity.

RESULTS: A total of 98 patients completed the study. Sixty-two underwent PD (63.3%) and 36 underwent DP (36.7%). The primary outcome was observed in eight (8%) patients in the overall cohort, one from the DP group and seven from the PD group. Biochemical leak was detected in 12 (12.2%) patients in the overall cohort. Twenty-seven (27.5%) patients developed complications, of which 14 (14.2%) were major complications. Drug-related adverse events were limited to mild skin reactions in two (2%) patients.

CONCLUSION: Patients who received preoperative lanreotide developed CR-POPF at rates significantly lower than historical controls or published literature. This provides strong justification for a randomized controlled trial.

PMID:35953409 | DOI:10.1016/j.hpb.2022.07.011

Gut Microbes. 2022 Jan-Dec;14(1):2108655. doi: 10.1080/19490976.2022.2108655.

ABSTRACT

As Helicobacter pylori management has become more challenging and less efficient over the last decade, the interest in innovative interventions is growing by the day. Probiotic co-supplementation to antibiotic therapies is reported in several studies, presenting a moderate reduction in drug-related side effects and a promotion in positive treatment outcomes. However, the significance of gut microbiota involvement in the competence of probiotic co-supplementation is emphasized by a few researchers, indicating the alteration in the host gastrointestinal microbiota following probiotic and drug uptake. Due to the lack of long-term follow-up studies to determine the efficiency of probiotic intervention in H. pylori eradication, and the delicate interaction of the gut microbiota with the host wellness, this review aims to discuss the gut microbiota alteration by probiotic co-supplementation in H. pylori management to predict the comprehensive effectiveness of probiotic oral administration.Abbreviations: acyl-CoA- acyl-coenzyme A; AMP- antimicrobial peptide; AMPK- AMP-activated protein kinase; AP-1- activator protein 1; BA- bile acid; BAR- bile acid receptor; BCAA- branched-chain amino acid; C2- acetate; C3- propionate; C4- butyrate; C5- valeric acid; CagA- Cytotoxin-associated gene A; cAMP- cyclic adenosine monophosphate; CD- Crohn's disease; CDI- C. difficile infection; COX-2- cyclooxygenase-2; DC- dendritic cell; EMT- epithelial-mesenchymal transition; FMO- flavin monooxygenases; FXR- farnesoid X receptor; GPBAR1- G-protein-coupled bile acid receptor 1; GPR4- G protein-coupled receptor 4; H2O2- hydrogen peroxide; HCC- hepatocellular carcinoma; HSC- hepatic stellate cell; IBD- inflammatory bowel disease; IBS- irritable bowel syndrome; IFN-γ- interferon-gamma; IgA immunoglobulin A; IL- interleukin; iNOS- induced nitric oxide synthase; JAK1- janus kinase 1; JAM-A- junctional adhesion molecule A; LAB- lactic acid bacteria; LPS- lipopolysaccharide; MALT- mucosa-associated lymphoid tissue; MAMP- microbe-associated molecular pattern; MCP-1- monocyte chemoattractant protein-1; MDR- multiple drug resistance; mTOR- mammalian target of rapamycin; MUC- mucin; NAFLD- nonalcoholic fatty liver disease; NF-κB- nuclear factor kappa B; NK- natural killer; NLRP3- NLR family pyrin domain containing 3; NOC- N-nitroso compounds; NOD- nucleotide-binding oligomerization domain; PICRUSt- phylogenetic investigation of communities by reconstruction of unobserved states; PRR- pattern recognition receptor; RA- retinoic acid; RNS- reactive nitrogen species; ROS- reactive oxygen species; rRNA- ribosomal RNA; SCFA- short-chain fatty acids; SDR- single drug resistance; SIgA- secretory immunoglobulin A; STAT3- signal transducer and activator of transcription 3; T1D- type 1 diabetes; T2D- type 2 diabetes; Th17- T helper 17; TLR- toll-like receptor; TMAO- trimethylamine N-oxide; TML- trimethyllysine; TNF-α- tumor necrosis factor-alpha; Tr1- type 1 regulatory T cell; Treg- regulatory T cell; UC- ulcerative colitis; VacA- Vacuolating toxin A.

PMID:35951774 | DOI:10.1080/19490976.2022.2108655

Genet Med. 2022 Aug 10:S1098-3600(22)00820-6. doi: 10.1016/j.gim.2022.06.011. Online ahead of print.

ABSTRACT

PURPOSE: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance.

METHODS: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation.

RESULTS: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work.

CONCLUSION: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population.

PMID:35951014 | DOI:10.1016/j.gim.2022.06.011

J Cardiol Cases. 2022 Apr 25;26(2):148-150. doi: 10.1016/j.jccase.2022.04.001. eCollection 2022 Aug.

ABSTRACT

Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug, that has successfully been used for the treatment of rheumatoid arthritis and psoriatic arthritis as a feasible alternative to methotrexate. Among side effects, pulmonary arterial hypertension (PAH) has been described in a few case reports.We present a 55-year-old woman treated with leflunomide for psoriatic spondyloarthritis who consulted our hospital because of progressive exertional dyspnea. Clinical examination found signs of right heart failure and severe pre-capillary pulmonary hypertension (PH) was diagnosed by right heart catheterization. All investigations for pre-capillary PH were negative and a diagnosis of severe PAH was thus established. Due to previous evidence of the association of leflunomide with PAH, the drug was stopped and upfront dual combination therapy with pulmonary vasodilators was initiated. The patient's condition rapidly improved with significant improvement in exercise tolerance and normalization of echocardiographic right ventricular systolic pressure within three months of treatment.

LEARNING OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare disease and drug-induced causes account for only a small percentage of these patients. In recent years, new drugs have been identified or suspected as potential risk factors for PAH. Among these, leflunomide, a disease-modifying antirheumatic drug, has been associated with PAH only in a few case reports. An accurate drug history is strongly recommended for all patients in which a PAH is newly diagnosed.

PMID:35949584 | PMC:PMC9352420 | DOI:10.1016/j.jccase.2022.04.001

BMC Pharmacol Toxicol. 2022 Aug 10;23(1):62. doi: 10.1186/s40360-022-00603-4.

ABSTRACT

BACKGROUND: Cutaneous adverse drug reaction (CADR) is a common problem in clinical medication. This study aimed to investigate the correlation between clinical drug application and CADR occurrence as evidence for preventive strategies and rational clinical drug use.

METHODS: We analyzed the characteristics of CADRs of 858 patients admitted to Shandong Provincial Third Hospital from March 2007 to December 2018. The most significant drugs concerning the common skin symptoms and their significance to CADR were investigated by case-non-case and multiple logistic regression analyses.

RESULTS: A total of 266 drugs were involved in 858 cases of CADR. Among the ten most relevant medications, primarily antibiotics and herbal injections, and nutritional support drugs, potassium sodium dehydroandrographolide succinate injection, and cefoperazone sodium and sulbactam sodium injection were found to be 2.1 and 1.45 times statistically more prone to CADRs than to other adverse drug reactions (ADRs), respectively. The main route of administration was intravenous (63.16%), with oral administration accounting for 25.19%. There were 747 cases of ADR, 71 of severe ADR, 2 of new and severe ADRs, and 38 cases of new ADR. Overall, 100 cases of CADR exhibited abnormal alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels. The predictive factors for severe CADR occurrence included allergy and smoking histories, cefoperazone sodium, sulbactam sodium injection, levofloxacin lactate and sodium chloride injection.

CONCLUSIONS: Drug-induced CADR symptoms are commonly associated with other ARDs, predominantly rashes and pruritus, and are often accompanied by some medical conditions, especially liver and kidney damage. Detailed attention to a patient's primary diseases, allergy history, and drug safety profile could help prevent or reverse CADR in most patients.

PMID:35948985 | DOI:10.1186/s40360-022-00603-4

Pharmacogenet Genomics. 2022 Sep 1;32(7):257-267. doi: 10.1097/FPC.0000000000000470. Epub 2022 Jul 21.

ABSTRACT

OBJECTIVE: To assess the impact of cytochrome P450 (CYP) 2C19 polymorphisms on the clinical efficacy and safety of voriconazole.

METHODS: We systematically searched PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases from their inception to 18 March 2021 using a predefined search algorithm to identify relevant studies. Studies that reported voriconazole-treated patients and information on CYP2C19 polymorphisms were included. The efficacy outcome was success rate. The safety outcomes included overall adverse events, hepatotoxicity, and neurotoxicity.

RESULTS: A total of 20 studies were included. Intermediate metabolizers (IMs) and poor metabolizers (PMs) were associated with increased success rates compared with normal metabolizers (NMs) [risk ratio (RR), 1.18; 95% confidence interval (CI), 1.03-1.34; I2 = 0%; P = 0.02; RR, 1.28; 95% CI, 1.06-1.54; I2 = 0%; P = 0.01]. PMs were at increased risk of overall adverse events in comparison with NMs and IMs (RR, 2.18; 95% CI, 1.35-3.53; I2 = 0%; P = 0.001; RR, 1.80; 95% CI, 1.23-2.64; I2 = 0%; P = 0.003). PMs demonstrated a trend towards an increased incidence of hepatotoxicity when compared with NMs (RR, 1.60; 95% CI, 0.94-2.74; I2 = 27%; P = 0.08), although there was no statistically significant difference. In addition, there was no significant association between CYP2C19 polymorphisms and neurotoxicity.

CONCLUSION: IMs and PMs were at a significant higher success rate in comparison with NMs. PMs were significantly associated with an increased incidence of all adverse events compared with NMs and IMs. Researches are expected to further confirm these findings. Additionally, the relationship between hepatotoxicity and CYP2C19 polymorphisms deserves clinical attention.

PMID:35947050 | DOI:10.1097/FPC.0000000000000470

Medicine (Baltimore). 2022 Aug 5;101(31):e29473. doi: 10.1097/MD.0000000000029473.

ABSTRACT

RATIONALE: The introduction of immune-checkpoint inhibitors (ICPI) in recent years has changed the natural course of many neoplasms. However, patients receiving these medications may present immune-mediated adverse events; management includes temporary or permanent cessation of treatment and corticosteroids, occasionally combined with other immunomodulators. Such immunosuppression, however, also has numerous adverse events and even if it is effective in controlling toxicity, it delays immunotherapy reinitiation, as current evidence requires dose tapering to ≤10 mg prednisolone equivalent before rechallenge. Enteric-coated budesonide is a corticosteroid formulation acting primarily to the intestine and liver, as a result of its extensive first-pass hepatic metabolism.

PATIENT CONCERNS: A 76-year-old woman treated with ipilimumab for metastatic melanoma presented with abdominal pain, vomiting, and diarrhea for at least the previous 4 days. Laboratory tests, among others, revealed elevated aminotransferases and C-reactive protein. During hospitalization, the patient also developed fever.

DIAGNOSIS: The patient, after excluding alternative causes of aminotransferase elevation, was diagnosed with grade 3 ipilimumab-associated hepatotoxicity.

INTERVENTIONS: Budesonide monotherapy was administered; initial daily dose was 12 mg.

OUTCOMES: Fever subsided after the first dose of budesonide. Aminotransferases returned to normal-near normal approximately 1 month after the first dose of budesonide. After this point, daily dose was reduced by 3 mg every 2 weeks, with no clinical or biochemical relapse.

CONCLUSIONS: This case of ICPI hepatitis is, to our knowledge, the first in the literature managed with budesonide monotherapy. Therefore, budesonide may be a potentially attractive option for the management of ICPI-associated liver injury in cases where corticosteroid treatment is necessary due to its safety profile and the potential advantage of faster immunotherapy rechallenge in selected patients without requiring dose tapering, in contrast to systemically acting corticosteroids. Clinical trials should be conducted in the future in order to validate or refute these findings.

PMID:35945730 | DOI:10.1097/MD.0000000000029473

Med J Aust. 2022 Aug 10. doi: 10.5694/mja2.51679. Online ahead of print.

NO ABSTRACT

PMID:35948314 | DOI:10.5694/mja2.51679

Med J Aust. 2022 Aug 10. doi: 10.5694/mja2.51681. Online ahead of print.

NO ABSTRACT

PMID:35948307 | DOI:10.5694/mja2.51681

Niger J Physiol Sci. 2022 Jun 30;37(1):119-126. doi: 10.54548/njps.v37i1.15.

ABSTRACT

The liver and the kidney are one of the vital organs of body. Drug-induced toxicity is one of the most common problems encountered by these organs. The search for an effective medicine to treat this toxicity without any side effects has led to the use of traditional-based medicine. This study evaluated the effect of ethanolic extract of Moringa oleifera seed oil on hepatic and renal markers in dimethyl 2, 2-dichlorovinyl phosphate (DDVP, known as dichlorvos)-exposed Wistar rats. Twenty-one male Wistar rats were randomly divided into three groups of seven animals each. Group A served as the negative control and were not exposed to dichlorvos. Group B served as the positive control and were exposed to dichlorvos for 2 minutes but received no extract. Group C animals were exposed to the dichlorvos and received 300mg/kg of extract (Moringa oleifera seed oil) for 7days before and 21days after exposure. Exposure to DDVP led to a significant increase in hepatic & renal markers, inflammatory markers, decrease in plasma protein and alteration of plasma electrolyte. Moringa oleifera seed oil regulated and significantly enhanced plasma protein, reduced elevated levels of hepatic & renal markers, inflammatory markers in the study sample. In addition, histopathology observation showed that Moringa seed oil was able to regenerate the hepatorenal damage on exposure to dichlorvos. Conclusion: Moringa oleifera seed oil exhibited hepato-protective, nephroprotective properties and could be explored in nutrition and health.

PMID:35947842 | DOI:10.54548/njps.v37i1.15

Arthritis Res Ther. 2022 Aug 9;24(1):191. doi: 10.1186/s13075-022-02868-w.

ABSTRACT

BACKGROUND: Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA.

METHODS: Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model.

RESULTS: Of the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255-0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235-0.797), breast cancer (0.146; 0.045-0.474), and genitourinary cancer (0.220; 0.059-0.820).

CONCLUSIONS: The use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.

PMID:35945635 | DOI:10.1186/s13075-022-02868-w

Inflamm Bowel Dis. 2022 Aug 9:izac140. doi: 10.1093/ibd/izac140. Online ahead of print.

ABSTRACT

Renal and urinary tract complications related to inflammatory bowel disease (IBD) have been relatively understudied in the literature compared with other extraintestinal manifestations. Presentation of these renal manifestations can be subtle, and their detection is complicated by a lack of clarity regarding the optimal screening and routine monitoring of renal function in IBD patients. Urolithiasis is the most common manifestation. Penetrating Crohn's disease involving the genitourinary system as an extraintestinal complication is rare but associated with considerable morbidity. Some biologic agents used to treat IBD have been implicated in progressive renal impairment, although differentiating between drug-related side effects and deteriorating kidney function due to extraintestinal manifestations can be challenging. The most common findings on renal biopsy of IBD patients with renal injury are tubulointerstitial nephritis and IgA nephropathy, the former also being associated with drug-induced nephrotoxicity related to IBD medication. Amyloidosis, albeit rare, must be diagnosed early to reduce the chance of progression to renal failure. In this review, we evaluate the key literature relating to renal and urological involvement in IBD and emphasize the high index of suspicion required for the prompt diagnosis and treatment of these manifestations and complications, considering the potential severity and implications of acute or chronic loss of renal function. We also provide suggestions for future research priorities.

PMID:35942657 | DOI:10.1093/ibd/izac140

BMC Public Health. 2022 Aug 8;22(1):1506. doi: 10.1186/s12889-022-13898-z.

ABSTRACT

BACKGROUND: The European Medicines Agency (EMA) requires enhanced safety surveillance to be conducted for annual seasonal influenza vaccines with the aim of rapidly detecting any potential new safety concerns before the peak immunisation period of the vaccine in any given year. The aim of this study was to detect any clinically significant change in the frequency or severity of expected reactogenicity of the quadrivalent inactivated split-virion influenza vaccine (IIV4) during routine immunisation in Finland for the 2020/21 season. The primary objective was to investigate the frequency of suspected adverse drug reactions (ADRs) occurring within 7 days following vaccination.

METHODS: Enhanced passive safety surveillance of individuals vaccinated with IIV4 was conducted from October 9, 2020 to November 30, 2020 across seven sites in Finland. The vaccinee reporting rate and ADR reporting rate were calculated and compared with known or expected safety data in order to identify any clinically significant changes.

RESULTS: Data were collected from 1008 individuals with 29 vaccinees reporting 82 suspected ADRs. Of these, 28 people reported 79 suspected ADRs within 7 days following vaccination, corresponding to a vaccinee reporting rate of 2.78% (95% CI: 1.85, 3.99) (ADR reporting rate, 7.84% [95% CI: 6.25, 9.67%]). The most frequently reported ADRs were injection site reactions (vaccination site pain, vaccination site erythema and vaccination site swelling) (n = 46, 2.28%), myalgia (n = 9, 0.89%) and headache (n = 8, 0.79%). No serious suspected adverse events were reported at any point post-vaccination and ADR reporting rates were in general lower compared to those reported for IIV4 in the 2019/20 surveillance study.

CONCLUSION: No clinically significant changes in what is known or expected for IIV4 were reported for the 2020/21 season which supports the safety profile of this vaccine and will help maintain public confidence in influenza vaccination.

PMID:35941631 | DOI:10.1186/s12889-022-13898-z

J Nutr Health Aging. 2022;26(8):778-785. doi: 10.1007/s12603-022-1825-5.

ABSTRACT

OBJECTIVES: To investigate concerns surrounding the benefits of antiresorptive drugs in older adults, a systematic review was carried out to evaluate the efficacy of these treatments in the prevention of osteoporotic hip fractures in older adults.

DESIGN: a systematic review and meta-analysis of randomized clinical trials.

SETTING AND PARTICIPANTS: older adults ≥65 years with osteoporosis, with or without a previous fragility fracture. Studies with cancer-related and corticosteroid-induced osteoporosis, participants <65 years and no reported hip fracture were not included.

METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science and Scopus databases were searched. The primary outcome was hip fracture, and subgroup analysis (≥75 years, with different drug types and secondary prevention) and sensitivity analysis was carried out using a GRADE evaluation. Secondary outcomes were any type of fractures, vertebral fracture, bone markers and adverse events. The risk of bias was assessment with the Cochrane risk of bias tool.

RESULTS: A total of 12 randomised controlled trials (RCTs) qualified for this meta-analysis, with 36,196 participants. Antiresorptive drugs have a statistically significant effect on the prevention of hip fracture (RR=0.70; 95%CI 0.60 to 0.81), but with a moderate GRADE quality of evidence and a high number needed to treat (NNT) of 186. For other outcomes, there is a statistically significant effect, but with a low to moderate quality of evidence. Antiresorptives showed no reduction in the risk of hip fracture in people ≥75 years. The results for different drug types, secondary prevention and sensitivity analysis are similar to the main analyses and have the same concerns.

CONCLUSIONS: Antiresorptive drugs have a statistically significant effect on preventing hip fracture but with a moderate quality (unclear/high risk of bias) and high NNT (186). This small benefit disappears in those ≥75 years, but increases in secondary prevention. More RCTs in very old osteoporotic adults are needed.

PMID:35934822 | DOI:10.1007/s12603-022-1825-5

Regul Toxicol Pharmacol. 2022 Aug 4:105236. doi: 10.1016/j.yrtph.2022.105236. Online ahead of print.

ABSTRACT

JNJ-10450232 (NTM-006) is a new molecular entity that comprises structural similarities to acetaminophen and provides comparable analgesia in animals and humans without causing the hepatotoxicity associated with acetaminophen overdose in preclinical models. This double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of JNJ-10450232 (NTM-006) following single (50-6000 mg) and multiple (250-2500 mg twice daily for 8 days) doses in healthy male volunteers. JNJ-10450232 (NTM-006) was absorbed within 1-3 h, except at high doses at which Cmax was delayed and bimodal, while increases in AUC were more than dose proportional. CL/F and Vd/F decreased approximately 3-fold with increasing single doses up to 6000 mg and multiple doses up to 1000 mg, resulting in similar t½ values that ranged from 8-10 h across doses. JNJ-10450232 (NTM-006) was generally safe and well tolerated, and no dose-limiting toxicities were observed. Transient increases in indirect bilirubin were noted at post-baseline timepoints due to UGT1A1 inhibition, without any evidence of adverse hepatic effects. Macular rash and generalized erythema were the most common drug-related adverse events after multiple doses.

PMID:35934140 | DOI:10.1016/j.yrtph.2022.105236

Ital J Pediatr. 2022 Aug 4;48(1):140. doi: 10.1186/s13052-022-01334-2.

ABSTRACT

Infantile hemangiomas may affect the quality of life (QoL) of patients and their family members, as anxiety and worry may commonly occur in parents, also linked to the social adversion they experience. We underline the beneficial impact of oral propranolol therapy on QoL of patients with infantile hemangiomas (IH) and of their relatives. A specific questionnaire measuring QoL was administered to parents of IH patients at beginning and end of a treatment with oral propranolol. Different aspects were investigated: site of the lesion, age of patients at starting therapy, length of treatment, occurrence of adverse effects and persistence/recurrence of the vascular anomaly. In all cases the questionnaire revealed a significant improvement of QoL, which was independent from all analyzed factors. It showed that oral propranolol administration in these patients combines optimal clinical results with relevant improvement of QoL, especially in cases of early management. The improvement of QoL seems unrelated to site of lesion, timing and duration of therapy, occurrence of drug-related adverse effects and persistence/recurrence of disease.

PMID:35927685 | PMC:PMC9351120 | DOI:10.1186/s13052-022-01334-2

PLoS One. 2022 Aug 4;17(8):e0270595. doi: 10.1371/journal.pone.0270595. eCollection 2022.

ABSTRACT

Allergic reactions to medication range from mild to severe or even life-threatening. Proper documentation of patient allergy information is critical for safe prescription, avoiding drug interactions, and reducing healthcare costs. Allergy information is regularly obtained during the medical interview, but is often poorly documented in electronic health records (EHRs). While many EHRs allow for structured adverse drug reaction (ADR) reporting, a free-text entry is still common. The resulting information is neither interoperable nor easily reusable for other applications, such as clinical decision support systems and prescription alerts. Current approaches require pharmacists to review and code ADRs documented by healthcare professionals. Recently, the effectiveness of machine algorithms in natural language processing (NLP) has been widely demonstrated. Our study aims to develop and evaluate different NLP algorithms that can encode unstructured ADRs stored in EHRs into institutional symptom terms. Our dataset consists of 79,712 pharmacist-reviewed drug allergy records. We evaluated three NLP techniques: Naive Bayes-Support Vector Machine (NB-SVM), Universal Language Model Fine-tuning (ULMFiT), and Bidirectional Encoder Representations from Transformers (BERT). We tested different general-domain pre-trained BERT models, including mBERT, XLM-RoBERTa, and WanchanBERTa, as well as our domain-specific AllergyRoBERTa, which was pre-trained from scratch on our corpus. Overall, BERT models had the highest performance. NB-SVM outperformed ULMFiT and BERT for several symptom terms that are not frequently coded. The ensemble model achieved an exact match ratio of 95.33%, a F1 score of 98.88%, and a mean average precision of 97.07% for the 36 most frequently coded symptom terms. The model was then further developed into a symptom term suggestion system and achieved a Krippendorff's alpha agreement coefficient of 0.7081 in prospective testing with pharmacists. Some degree of automation could both accelerate the availability of allergy information and reduce the efforts for human coding.

PMID:35925971 | PMC:PMC9352066 | DOI:10.1371/journal.pone.0270595