Ther Adv Musculoskelet Dis. 2022 Dec 19;14:1759720X221142274. doi: 10.1177/1759720X221142274. eCollection 2022.

ABSTRACT

BACKGROUND: No data on the permanent and curative effect of bisphosphonate treatment in patients with complex regional pain syndrome type-1 (CRPS-1) are currently available. The aim of this pre-specified, open-label, observational study was to evaluate the long-term efficacy and safety of neridronate treatment.

DESIGN: A pre-specified, open-label, extension study.

METHODS: Patients treated with intramuscular (IM) placebo in the double-blind phase of the study were assigned to 100 mg intravenous (IV) neridronate treatment administered 4 times over 10 days. These patients, together with those previously treated with 400 mg IM neridronate, were followed for 1 year. Efficacy was assessed using a visual analogue scale (VAS) pain score. Changes in clinical signs and symptoms, quality of life (QoL) using the Short Form Health Survey (SF-36), and the McGill Pain Questionnaire were also assessed.

RESULTS: Benefits on pain, clinical and functional measures were maintained and further improved over 12 months in most patients treated with neridronate administered either IM or IV. In IM-treated patients, the percentage of those defined as responders (VAS score reduction ≥ 50%) progressively increased up to day 360 to 32 of 35 patients (91.4%). Among the 27 patients referred to as responders at the end of the double-blind phase, 26 reported the same result at day 360 (96.3%). In IV-treated patients, a responder rate of 88% (22 out 25) was found at day 360 (p = 0.66 between groups). Consistent improvements were also observed for all clinical signs and functional questionnaire. No drug-related adverse events were reported during the study.

CONCLUSION: In patients with acute CRPS-1, the benefit in pain, clinical, and functional measures observed a few weeks after neridronate treatment administered either IM or IV is maintained and further improved over 12 months. Parenteral neridronate induces permanent disease remission preventing chronic pain and motor dysfunction.

TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT Number): 2014-001156-28.

PMID:36569491 | PMC:PMC9772942 | DOI:10.1177/1759720X221142274

Front Pharmacol. 2022 Dec 9;13:1067686. doi: 10.3389/fphar.2022.1067686. eCollection 2022.

ABSTRACT

Background: Postmarketing safety analysis is an effective supplement for new drugs in clinical practice. Therefore, we aimed to systematically assess the safety of oral nemonoxacin malate, the first approved C-8-methoxy non-fluorinated quinolone, in clinical studies and via postmarketing safety surveillance. Methods: We electronically and manually searched and screened safety data (including premarketing and postmarketing data) of oral nemonoxacin from clinical registries. We standardized and summarized the reported adverse events according to the Medical Dictionary for Regulatory Activities System Organ Class and Preferred Terms. We summarized and reported the number and frequency (%) of the AEs and serious AEs in patients with community-acquired pneumonia and in specific patients. Results: Three Phase II/III comparator studies (n = 670, nemonoxacin), one Phase IV study (n = 461), two special population pharmacokinetic studies (n = 40), four observational studies (n = 1,852), and one 5-year postmarketing surveillance project (n = 257,420) were included in this study. The Phase II/III studies showed that the commonly reported drug-related AEs were similar for oral 500 mg nemonoxacin and levofloxacin treatments, which mainly included increased alanine aminotransferase levels (4.4% vs. 2.5%), neutropenia (2.5% vs. 4.4%), nausea (2.5% vs. 1.6%), and leukopenia (2.3% vs. 3.2%). No drug-related deaths were reported. Postmarketing safety surveillance revealed that known adverse drug reaction characteristics were generally unchanged. Pharmacokinetic data suggested that dose adjustment was not necessary in elderly patients, which was confirmed by a Phase IV study in an elderly population, in patients with renal impairment with CLcr ≥50 ml/min, and in those with mild-to-moderate hepatic impairment. Conclusion: Clinical trial data of approximately 1,450 patients and postmarketing data of >257,420 patients suggest that nemonoxacin is generally well tolerated and can be a suitable alternative to fluoroquinolones for patients with CAP.

PMID:36569296 | PMC:PMC9780658 | DOI:10.3389/fphar.2022.1067686

Acta Gastroenterol Belg. 2022 Oct-Dec;85(4):587-592. doi: 10.51821/85.4.10634.

ABSTRACT

BACKGROUND AND STUDY AIM: Entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF), and Tenofovir Alafenamide (TAF) have been approved for treating Chronic Hepatitis B (CHB) and recommended due to their high safety profile and high resistance barriers. This study aimed to evaluate the kidney functions, bone, and metabolic parameters in CHB patients receiving ETV, TDF, and TAF treatment.

PATIENTS AND METHODS: In this retrospective cohort study, a total of 469 CHB patients who were treated with TDF (n = 256), ETV (n = 184), or TAF (n = 129) for at least six months between March 2012 and March 2022, were enrolled.

RESULTS: No significant difference was observed between three groups regarding ALT normalization, HBV DNA suppression, and HBs Ag seroconversion (p = 0.15, p = 0.26, p = 0.72). After the treatment, there was a significant decrease in GFR values in the TDF, ETV, and TAF groups (p<0.01, p = 0.01, p = 0.01, respectively). No significant improvement was observed in the GFR values after TAF treatment in 77 patients who had switched from TDF to TAF (p = 0.51). Moreover, no significant decrease in bone mineral densities was observed in the TDF, ETV, and TAF groups (p = 0.24, p = 0.41, p = 0.95, respectively). There was no significant difference between the three groups in metabolic parameters (serum glucose, lipid profile, calcium and phosphorus levels, etc.) when the data were adjusted for underlying comorbidities.

CONCLUSIONS: ETV, TDF, and TAF are comparably safe and effective antiviral agents against CHB.

PMID:36566368 | DOI:10.51821/85.4.10634

Am J Addict. 2022 Dec 25. doi: 10.1111/ajad.13366. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Adverse events during childhood increase the risk for the development of substance use disorders (SUDs). This study examined the association between adverse childhood experiences (ACEs) and SUD treatment response.

METHODS: This cohort analysis included data from longitudinal clinical assessments extracted from the records of 438 consenting individuals undergoing SUD treatment (63% male; 88.8% White). Mixed effects models evaluated the relationship between scores on the ACE questionnaire and indicators of treatment response (i.e., alcohol and drug abstinence self-efficacy; symptoms of depression, anxiety, and posttraumatic stress disorder) for individuals with alcohol-related (n = 332) and other drug-related (n = 275) diagnoses, with some participants included in both groups.

RESULTS: Treatment response varied as a function of ACEs, with the magnitude of differences varying across time in treatment. Relative to those with no ACE history, those who experienced ≥2 ACEs reported worse depression, anxiety, PTSD symptoms, and alcohol/drug abstinence self-efficacy at baseline, with many differences remaining at the 30-day assessment. All differences abated by discharge, with the exception of PTSD symptoms among those in the drug use group with a history of ≥4 ACEs. Male gender and older age were generally associated with lower symptomology and higher abstinence self-efficacy.

DISCUSSION AND CONCLUSIONS: Assessing ACE history early in SUD treatment may improve treatment planning and prognosis. Future studies should evaluate the role of trauma-informed programming and individual interventions to improve treatment response.

SCIENTIFIC SIGNIFICANCE: This study demonstrates the association between adverse childhood experiences and symptom severity among patients across participation in SUD treatment.

PMID:36566359 | DOI:10.1111/ajad.13366

BMC Infect Dis. 2022 Dec 24;22(1):959. doi: 10.1186/s12879-022-07925-y.

ABSTRACT

BACKGROUND: European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4 g/day) rather than standard dose (2 g/day) posology. This is particularly relevant for invasive infections, and for patients managed via Outpatient Parenteral Antimicrobial Therapy (OPAT), but may result in increased drug toxicity. We quantified the incidence of neutropenia, thrombocytopenia and raised liver enzymes between standard and high dose ceftriaxone in adult patients.

METHOD: Adult outpatients prescribed ≥ 7 days of ceftriaxone therapy were identified, and clinical, pharmacological, and laboratory parameters extracted from electronic health records between May 2021 and December 2021. Incidence and median time to haematological and hepto-toxicity were analysed. Univariate odds ratios were calculated for neutrophil count and ALT levels with 95% confidence level and Chi squared/Fisher's exact test used to identify statistical significance.

RESULTS: Incidence of neutropenia was comparable between both groups; 8/47 (17%) in the 2 g group vs 6/39 (15.4%) in the 4 g group (OR 0.89 (95% CI 0.26-2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2 g and 4 g groups respectively. Thrombocytopenia was observed in 0/47 in the 2 g group compared with 3/39 (7.7%) in the 4 g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4 g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2 g and 4 g respectively (OR 0.45 (95% CI 0.87-2.36), p 0.448). Treatment cessation due to any adverse effect was similar between both groups 2/47 (4.3%) for 2 g and 3/39 (7.7%) for 4 g (OR 1.86 (95% CI 0.36-10.92), p 0.655).

CONCLUSIONS: Increased adverse effects with 4 g (over 2 g) daily dosing of ceftriaxone was not observed in an OPAT population. However absolute development of haematological and liver dyscrasias was appreciable-monitoring of liver function and full blood count in patients receiving prolonged ceftriaxone is indicated irrespective of dosing.

PMID:36566229 | DOI:10.1186/s12879-022-07925-y

Pediatr Allergy Immunol. 2022 Dec;33(12):e13887. doi: 10.1111/pai.13887.

ABSTRACT

BACKGROUND: Dupilumab has proven to be an effective and safe treatment for atopic dermatitis (AD) in pediatric patients in clinical trials. However, few daily practice studies are available. The aim of this study is to evaluate the effect of 28 weeks dupilumab treatment on effectiveness, safety, and serum biomarkers in pediatric patients with moderate-to-severe AD in daily practice.

METHODS: Patients visited the outpatient clinic at baseline, 4, 16, and 28 weeks of treatment. Disease severity was assessed by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Numeric Rating Scale (NRS)-pruritus and -pain, and the Patient-Oriented Eczema Measure (POEM). Side effects were evaluated. Nineteen severity-associated serum biomarkers were measured. Predicted-EASI (p-EASI) was calculated.

RESULTS: Sixty-one patients were included. Respectively 75.4%, 49.2%, and 24.6% reached EASI-50, EASI-75, and EASI-90 and 36.1% achieved an IGA-score (almost) clear. Improvement of ≥4 points on POEM, NRS-pruritus, and NRS-pain was reached by 84.7%, 45.3%, and 77.4%, respectively. Most reported side effects were conjunctivitis (n = 10) and headache (n = 4). Biomarkers TARC, PARC, periostin, sIL-2Ra, and eotaxin-3 significantly decreased during treatment. The p-EASI showed a significant correlation with disease severity.

CONCLUSION: Dupilumab treatment significantly improved disease severity and disease-associated symptoms and decreased severity-associated serum biomarkers in pediatric AD patients in daily practice.

PMID:36564878 | DOI:10.1111/pai.13887

Int J Clin Pharm. 2022 Dec 24. doi: 10.1007/s11096-022-01526-0. Online ahead of print.

ABSTRACT

BACKGROUND: In France, hospital pharmacists perform medication order reviews during patients' hospital stays. This activity can be centralized in the pharmacy or carried out directly in the ward, in collaboration with the healthcare team. During this review, pharmacists can make recommendations to optimize therapeutics. Since 2006, they can document their interventions, via the national Act-IP© observatory.

AIM: To determine the characteristics of pharmacists' interventions and their acceptance by physicians in French hospitals.

METHOD: A 6-year observational study of pharmacists' interventions documented on the Act-IP© French observatory between 2009 and 2014 was performed. Multiple logistic regression was undertaken to determine the predictors of physicians' acceptance of interventions.

RESULTS: A total of 194,684 pharmacists' interventions were documented and concerned mainly "dosage adjustment" (25.6%). These interventions were mostly related to drugs from the central nervous system (23.7%). Seventy percent of pharmacists' interventions were accepted by physicians. Acceptance rate was higher when conducted by a pharmacist regularly practicing in the ward (ORa = 1.60, CI 95 [1.57-1.64]). Physicians' acceptance was significantly associated with (1) ward specialty: emergency (ORa = 1.24, CI 95 [1.14-1.35]); (2) type of intervention: "drug discontinuation", "drug switch" (ORa = 1.15, CI 95 [1.12-1.19]) and "addition of a new drug" (ORa = 1.15, CI 95 [1.12-1.19]); (3) drug group: antineoplastic and immunomodulators (ORa = 3.67, CI 95 [3.44-3.92]).

CONCLUSION: This 6-year longitudinal study highlights the role of clinical pharmacists, and particularly the impact of those integrated into wards. This was found to improve intervention acceptance, potentially through collaboration with physicians in pursuit of patient care and drug safety.

PMID:36566276 | DOI:10.1007/s11096-022-01526-0

Med Oncol. 2022 Dec 23;40(1):58. doi: 10.1007/s12032-022-01932-4.

ABSTRACT

Oral cryotherapy (OC) is a common preventive treatment of oral mucositis (OM) and is recommended in international guidelines. Ice and air OC have previously been shown to result in temperature reductions of 8.1-12.9 °C, and 14.5 °C, respectively, in healthy volunteers. However, no direct comparison between these two modalities has been performed. The primary aim was to investigate the tolerability and side effects of air OC using an intra-oral air-cooling (IOAC) device compared with ice OC. The secondary aim was to evaluate the temperature reduction in the mouth for the two respective methods. Cross-over study with randomization to order of treatment, in 15 healthy volunteers. We evaluated the self-reported intensity, frequency, and discomfort for 13 pre-defined side effects used in previous studies. All participants were able to complete both OC sessions, although one participant required reduced airflow in the air OC arm. The subjects reported more discomfort from being cold, having sensitive teeth, and numbness in the ice OC group, while they reported more discomfort from swallowing when subjected to air OC. No significant difference in the median temperature reduction was detected in the two modalities, except for the dorsal posterior part of the tongue where temperature reduction was larger in the ice OC group. We found that oral cooling using a new IOAC device was tolerated and seems to be safe in healthy volunteers.

PMID:36562896 | PMC:PMC9789000 | DOI:10.1007/s12032-022-01932-4

Medicina (Kaunas). 2022 Dec 6;58(12):1799. doi: 10.3390/medicina58121799.

ABSTRACT

Background: Individuals with underlying chronic illnesses have demonstrated considerable hesitancy towards COVID-19 vaccines. These concerns are primarily attributed to their concerns over the safety profile. Real-world data on the safety profile among COVID-19 vaccinees with comorbid conditions are scarce. This study aimed to ascertain the side-effects profile after two doses of COVID-19 vaccines among chronic-disease patients. Methodology: A cross-sectional questionnaire-based study was conducted among faculty members with comorbid conditions at a public educational institute in Saudi Arabia. A 20-item questionnaire recorded the demographics and side effects after the two doses of COVID-19 vaccines. The frequency of side effects was recorded following each dose of vaccine, and the association of the side-effects score with the demographics was ascertained through appropriate statistics. Results: A total of 204 patients with at least one comorbid condition were included in this study. A total of 24 side effects were reported after the first dose and 22 after second dose of the COVID-19 vaccine. The incidence of at least one side effect was 88.7% and 95.1% after the first and second doses of the vaccine, respectively. The frequent side effects after the first dose were pain at the injection site (63.2%), fatigue (58.8%), fever (47.5%), muscle and joint pain (38.7%), and headache (36.3%). However, pain at the injection site (71.1%), muscle and joint pain (62.7%), headache (49.5%), fever (45.6%), and stress (33.3%) were frequent after the second dose. The average side-effects score was 4.41 ± 4.18 (median: 3, IQR: 1, 6) and 4.79 ± 3.54 (median 4, IQR: 2, 6) after the first and second dose, respectively. Female gender, diabetes mellitus, hypertension, hyperlipidemia, comorbidity &gt; 2, family history of COVID-19, and the AstraZeneca vaccine were significantly associated with higher side-effect scores. Only 35.8% of study participants were satisfied with the safety of COVID-19 vaccines. Conclusions: Our analysis showed a high proportion of transient and short-lived side effects of Pfizer and AstraZeneca vaccines among individuals with chronic illnesses. However, the side-effects profile was comparable with the safety reports of phase 3 clinical trials of these vaccines. The frequency of side effects was found to be associated with certain demographics, necessitating the need for further investigations to establish a causal relationship. The current study's findings will help instill confidence in the COVID-19 vaccines among people living with chronic conditions, overcome vaccine hesitancy, and increase vaccine coverage in this population.

PMID:36557002 | PMC:PMC9783784 | DOI:10.3390/medicina58121799

Int J Mol Sci. 2022 Dec 19;23(24):16216. doi: 10.3390/ijms232416216.

ABSTRACT

Adverse drug reactions (ADRs) are a major issue to be addressed by the pharmaceutical industry. Early and accurate detection of potential ADRs contributes to enhancing drug safety and reducing financial expenses. The majority of the approaches that have been employed to identify ADRs are limited to determining whether a drug exhibits an ADR, rather than identifying the exact type of ADR. By introducing the "multi-level feature-fusion deep-learning model", a new predictor, called iADRGSE, has been developed, which can be used to identify adverse drug reactions at the early stage of drug discovery. iADRGSE integrates a self-attentive module and a graph-network module that can extract one-dimensional sub-structure sequence information and two-dimensional chemical-structure graph information of drug molecules. As a demonstration, cross-validation and independent testing were performed with iADRGSE on a dataset of ADRs classified into 27 categories, based on SOC (system organ classification). In addition, experiments comparing iADRGSE with approaches such as NPF were conducted on the OMOP dataset, using the jackknife test method. Experiments show that iADRGSE was superior to existing state-of-the-art predictors.

PMID:36555858 | PMC:PMC9786008 | DOI:10.3390/ijms232416216

Int J Mol Sci. 2022 Dec 9;23(24):15655. doi: 10.3390/ijms232415655.

ABSTRACT

Organ toxicity caused by chemicals is a serious problem in the creation and usage of chemicals such as medications, insecticides, chemical products, and cosmetics. In recent decades, the initiation and development of chemical-induced organ damage have been related to mitochondrial dysfunction, among several adverse effects. Recently, many drugs, for example, troglitazone, have been removed from the marketplace because of significant mitochondrial toxicity. As a result, it is an urgent requirement to develop in silico models that can reliably anticipate chemical-induced mitochondrial toxicity. In this paper, we have proposed an explainable machine-learning model to classify mitochondrially toxic and non-toxic compounds. After several experiments, the Mordred feature descriptor was shortlisted to be used after feature selection. The selected features used with the CatBoost learning algorithm achieved a prediction accuracy of 85% in 10-fold cross-validation and 87.1% in independent testing. The proposed model has illustrated improved prediction accuracy when compared with the existing state-of-the-art method available in the literature. The proposed tree-based ensemble model, along with the global model explanation, will aid pharmaceutical chemists in better understanding the prediction of mitochondrial toxicity.

PMID:36555297 | PMC:PMC9779353 | DOI:10.3390/ijms232415655

Int J Mol Sci. 2022 Dec 7;23(24):15480. doi: 10.3390/ijms232415480.

ABSTRACT

Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-19. To provide further insight into these glycan attachments and their potential clinical relevance, the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The electrostatic potential of the central region of spike protein from these four lineages was studied through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan sites. The results of these experiments were, first, that spike protein from these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower threshold concentration of spike protein than the three prior lineages and was much more electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterward. These results validate and extend prior findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore suggest therapeutic options using competitive glycan-binding agents such as IVM and may help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines, which use spike protein as the generated antigen.

PMID:36555121 | PMC:PMC9779393 | DOI:10.3390/ijms232415480

Int J Mol Sci. 2022 Dec 7;23(24):15470. doi: 10.3390/ijms232415470.

ABSTRACT

Cannabis contains over 500 distinct compounds, which include cannabinoids, terpenoids, and flavonoids. However, very few of these compounds have been studied for their beneficial effects. There is an emerging concept that the constituents of the cannabis plant may work in concert to achieve better therapeutic benefits. This study is aimed at determining if the combination of a minor cannabinoid (cannabidiol, CBD) and a terpene (beta-caryophyllene, BCP) works in concert and if this has any therapeutic value. We used an inflammatory pain model (formalin) in mice to test for any functionality of CBD and BCP in combination. First, we determined the analgesic effect of CBD and BCP individually by establishing dose-response studies. Second, we tested the analgesic effect of fixed-ratio combinations and monitored any adverse effects. Finally, we determined the effect of this combination on inflammation. The combination of CBD and BCP produces a synergistic analgesic effect. This effect was without the cannabinoid receptor-1 side effects. The analgesic effect of CBD and BCP in combination involves an inflammatory mechanism. The combination of these two constituents of the cannabis plant, CBD and BCP, works in concert to produce a therapeutic effect with safety profiles through an inflammatory mechanism.

PMID:36555111 | PMC:PMC9779834 | DOI:10.3390/ijms232415470

Drug Ther Bull. 2022 Dec 23:dtb-2022-000075. doi: 10.1136/dtb.2022.000075. Online ahead of print.

ABSTRACT

Overview of: European Medicines Agency Pharmacovigilance Risk Assessment Committee. Codeine with ibuprofen: PRAC adds warning for serious renal and gastrointestinal harms. September 2022.

PMID:36564156 | DOI:10.1136/dtb.2022.000075

Mol Biol Rep. 2022 Dec 23. doi: 10.1007/s11033-022-08158-7. Online ahead of print.

ABSTRACT

BACKGROUND: Anti-tuberculosis drug-induced liver injury (AT-DILI) is one of the most common side effects in TB patients during treatment. The prime cause of liver injury during TB treatment is reported to be isoniazid and its metabolites. Different factors influenced the development of AT-DILI, and genetic factors are one of the major factors.

METHODS AND RESULTS: Polymorphisms in drug metabolism genes like NAT2, CYP2E1, PXR, and GST have been reported to be associated with AT-DILI, and they are one of the major areas of focus at present. Attempts are met in this review to analyse the different markers in these drug metabolism genes for their association with AT-DILI.

CONCLUSION: A better understanding of the polymorphisms in these genes and their functional effects will give better insights into the development of AT-DILI, and it could facilitate in designing and developing more effective personalized treatment for TB.

PMID:36562936 | DOI:10.1007/s11033-022-08158-7

Vaccines (Basel). 2022 Dec 13;10(12):2137. doi: 10.3390/vaccines10122137.

NO ABSTRACT

PMID:36560547 | DOI:10.3390/vaccines10122137

Pharmaceuticals (Basel). 2022 Nov 22;15(12):1444. doi: 10.3390/ph15121444.

NO ABSTRACT

PMID:36558895 | DOI:10.3390/ph15121444

Medicina (Kaunas). 2022 Dec 15;58(12):1848. doi: 10.3390/medicina58121848.

NO ABSTRACT

PMID:36557050 | DOI:10.3390/medicina58121848

J Clin Med. 2022 Dec 19;11(24):7526. doi: 10.3390/jcm11247526.

NO ABSTRACT

PMID:36556142 | DOI:10.3390/jcm11247526

Healthcare (Basel). 2022 Dec 13;10(12):2523. doi: 10.3390/healthcare10122523.

NO ABSTRACT

PMID:36554047 | DOI:10.3390/healthcare10122523