Acta Derm Venereol. 2023 Feb 14;103:adv00867. doi: 10.2340/actadv.v103.3364.

NO ABSTRACT

PMID:36789755 | DOI:10.2340/actadv.v103.3364

Ital J Pediatr. 2023 Feb 14;49(1):20. doi: 10.1186/s13052-023-01427-6.

ABSTRACT

BACKGROUND: This study aimed to analyze all the patients who contacted the hospital's pediatric poison control center (PPCC) for exposure to ibuprofen and acetaminophen, in order to assess the incidence of any adverse reactions.

METHODS: We retrospectively reported the clinical data of children who accessed the PPCC of the Bambino Gesù Children's Hospital, IRCCS, Rome, from January 1, 2018 to September 30, 2022 due to wrong, accidental or intentional intake of inappropriate doses of acetaminophen and/or ibuprofen. In addition, we compared patients according to the intake of one of the two drugs and reported the trimestral distribution of cases during the study period.

RESULTS: A total of 351 patients accessed the PPCC during the study period. The median age was 3.0 years. Most patients were females (57.8%). The most common reason for inappropriate oral intake of paracetamol or ibuprofen was a wrong use or an accidental intake (78.6%), with a fifth of patients taking the drug with suicidal intent (21.1%). According to the PPCC evaluation, most patients were not intoxicated (70.4%). Hospitalization was required for 30.5% of patients. Adverse reactions were reported in 10.5% of cases, with a similar incidence in patients who took paracetamol or ibuprofen. Nausea and vomiting were the most commonly reported adverse reactions. A higher frequency of moderate intoxication was found in patients who took paracetamol compared to ibuprofen (p = 0.001). The likelihood of intoxication was also higher in the paracetamol cohort. A spike of cases was registered at the end of 2021.

CONCLUSIONS: We analyze exposures to the two most commonly used pediatric molecules, paracetamol and ibuprofen, to assess the frequency of adverse reactions. We demonstrated that these relatively "safe" drugs may be associated with intoxications and adverse reactions when inappropriately administered.

PMID:36788576 | DOI:10.1186/s13052-023-01427-6

BMC Med Inform Decis Mak. 2023 Feb 14;23(1):35. doi: 10.1186/s12911-023-02133-3.

ABSTRACT

BACKGROUND: The measurement of drug similarity has many potential applications for assessing drug therapy similarity, patient similarity, and the success of treatment modalities. To date, a family of computational methods has been employed to predict drug-drug similarity. Here, we announce a computational method for measuring drug-drug similarity based on drug indications and side effects.

METHODS: The model was applied for 2997 drugs in the side effects category and 1437 drugs in the indications category. The corresponding binary vectors were built to determine the Drug-drug similarity for each drug. Various similarity measures were conducted to discover drug-drug similarity.

RESULTS: Among the examined similarity methods, the Jaccard similarity measure was the best in overall performance results. In total, 5,521,272 potential drug pair's similarities were studied in this research. The offered model was able to predict 3,948,378 potential similarities.

CONCLUSION: Based on these results, we propose the current method as a robust, simple, and quick approach to identifying drug similarity.

PMID:36788528 | DOI:10.1186/s12911-023-02133-3

J Clin Oncol. 2023 Feb 20;41(6):1162-1171. doi: 10.1200/JCO.22.02499.

ABSTRACT

PURPOSE: To evaluate the efficacy and tolerability of two doses of gefitinib (Iressa [ZD1839]; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: This was a randomized, double-blind, parallel-group, multicenter phase II trial. Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens (at least one containing platinum) were randomized to receive either 250-mg or 500-mg oral doses of gefitinib once daily.

RESULTS: Efficacy was similar for the 250- and 500-mg/d groups. Objective tumor response rates were 18.4% (95% confidence interval [CI], 11.5 to 27.3) and 19.0% (95% CI, 12.1 to 27.9); among evaluable patients, symptom improvement rates were 40.3% (95% CI, 28.5 to 53.0) and 37.0% (95% CI, 26.0 to 49.1); median progression-free survival times were 2.7 and 2.8 months; and median overall survival times were 7.6 and 8.0 months, respectively. Symptom improvements were recorded for 69.2% (250 mg/d) and 85.7% (500 mg/d) of patients with a tumor response. Adverse events (AEs) at both dose levels were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent in the higher-dose group. Withdrawal due to drug-related AEs was 1.9% and 9.4% for patients receiving gefitinib 250 and 500 mg/d, respectively.

CONCLUSION: Gefitinib showed clinically meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients. At 250 mg/d, gefitinib had a favorable AE profile. Gefitinib 250 mg/d is an important, novel treatment option for patients with pretreated advanced NSCLC.

PMID:36791474 | DOI:10.1200/JCO.22.02499

Gut Liver. 2023 Feb 15. doi: 10.5009/gnl220457. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis.

METHODS: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events.

RESULTS: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups. No significant difference was noted in the incidence of adverse drug reactions.

CONCLUSIONS: Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).

PMID:36789577 | DOI:10.5009/gnl220457

BMC Prim Care. 2023 Feb 14;24(1):48. doi: 10.1186/s12875-023-02004-w.

ABSTRACT

BACKGROUND: Service gaps exist in oral anticoagulant (OAC) use among patients with atrial fibrillation (AF) in primary care. The purpose of this study was to explore the clinical effectiveness of a community dwelling Atrial Fibrillation Special Clinic (AFSC) run by primary care physicians by evaluating its impact on OAC use and the control of modifiable cardiovascular disease (CVD) risk factors in high risk AF patients.

METHOD: Quasi-experimental study was conducted in AFSC run by public primary care physicians in Hong Kong. Study subjects were high risk AF patients with CHA2DS2-VASc scores ≥ 2, who had been followed up (FU) at AFSC for at least one year from 01 August, 2019 to 31 October, 2020. OAC usage and modifiable CVD risk factor control were compared before and after one year of FU at AFSC. Drug-related adverse events, emergency attendance or hospitalisation episodes, survival and mortality rates after one year FU at AFSC were also reviewed.

RESULTS: Among the 299 high risk AF patients included in the study, significant increase in OAC use was observed from 58.5% at baseline to 82.6% after one year FU in AFSC (P < 0.001). Concerning CVD risk factor control, the average diastolic blood pressure level was significantly reduced (P = 0.009) and the satisfactory blood pressure control rate in non-diabetic patients was markedly improved after one year FU (P = 0.049). However, the average HbA1c and LDL-c levels remained static. The annual incidence rate of ischaemic stroke/systemic embolism was 0.4%, intra-cranial haemorrhage was 0.4%, major bleeding episode was 3.2% and all-cause mortality was 4.3%, all of which were comparable to reports in the literature.

CONCLUSION: AFSC is effective in enhancing OAC use and maintaining optimal modifiable CVD risk factor control among high risk AF patients managed in primary care setting, and therefore may reduce AF-associated morbidity and mortality in the long run.

PMID:36788489 | DOI:10.1186/s12875-023-02004-w

BMC Pediatr. 2023 Feb 13;23(1):77. doi: 10.1186/s12887-023-03891-9.

ABSTRACT

BACKGROUND: The characteristics and incidence of adverse drug events (ADEs) among pediatric cancer patients in developing countries have not been well characterized. ADEs & medication errors associated with cancer chemotherapy in children need to be analyzed on their incidence and severity. The purpose of this study was hence, to assess the incidence of adverse drug events and contributing factors among pediatric cancer patients at Jimma university medical center, Jimma, Ethiopia.

METHOD: A prospective observational method was used to study adverse drug events in pediatrics admitted to the pediatric oncology unit of Jimma University medical center between October and December 2020. The ADEs were identified using multifaceted approaches involving daily chart review, interviews of Parents/caregivers (and/or children themselves), attendance at ward rounds, and voluntary staff reports. Both univariate and multivariate logistic regression were used to assess the predictors of the identified ADEs. Those factors that showed association at p-value < 0.25 in the univariate analysis were added to the backward multivariate logistic regression model and the significant association was checked at p-value < 0.05.

RESULT: A total of 73 (46 male and 27 female) patients were included in the study. A total of 466 ADEs were identified with an incidence of 638.36 ADEs per 100 patients, 38.35 ADEs per 100 patient days, and 2.34 ADEs per chemotherapy cycle. The most common ADEs were hematologic toxicities (anemia 55(11.8%), neutropenia 52(11.16%) & thrombocytopenia 31(6.65%)), and gastrointestinal effects (nausea 46(9.87%), vomiting 46(9.87%), anorexia 41(8.8%). Out of 466 ADEs, 150 (32.19%) were classified as common terminology criteria for adverse events (CTCAE) as Grade 1, 199 (42.70%) as Grade 2, 64(13.73%) as Grade 3, 48(10.30%) as grade 4 and 5(1.07%) as Grade 5. Severe acute malnutrition (SAM) is the most common comorbidity present, 20(27.40%) followed by pneumonia, 4(5.50%). Presence of comorbidity (AOR 12.700, CI 1.978-81.549), cancer type (AOR 13.332, CI 3.288-54.059), use of 4 or more chemotherapy drugs (AOR 6.179, CI 1.894-20.165) and length of hospital stay more than 8 days (AOR 5.367, CI 1.167-24.684) were associated with the risk of developing grades 3 and 4 ADEs.

CONCLUSION: Adverse drug events were common in the pediatric oncology ward of JUMC. In particular, children with multiple chemotherapy drugs and those with the comorbid condition were at greater risk for adverse drug events.

PMID:36782170 | DOI:10.1186/s12887-023-03891-9

Eur J Hosp Pharm. 2023 Feb 14:ejhpharm-2022-003669. doi: 10.1136/ejhpharm-2022-003669. Online ahead of print.

ABSTRACT

OBJECTIVES: Optimal perioperative success in cardiac surgery requires precise management of drug treatment. This study aimed to determine the prevalence, types and associated factors of drug-related problems (DRPs) during the entire hospital stay.

METHODS: A prospective observational study was conducted at the department of cardiovascular surgery in a university hospital between November 2019 and March 2020. Patients with planned elective cardiac surgery, aged ≥18 years, were included. A clinical pharmacist collaboratively reviewed medications on a daily basis and identified DRPs.

RESULTS: A total of 100 patients (60 male) were included; median (range) age was 62 (19-86) years, and median (IQR) length of stay in hospital was 15 (9) days. A total of 275 DRPs were identified (median (IQR) 3 (2-4)). The number of patients who had at least one DRP was 47 preoperatively, 55 in the postoperative intensive care unit, 100 in the postoperative ward, and 16 at discharge. In order to reduce bias because of the small sample size, Firth's logistic regression analysis was conducted. Statistically significant variables according to univariate analysis were included into a logistic regression model. Therefore the length of hospital stay (OR 1.14, 95% CI 1.03 to 1.26, p=0.008), living arrangements (living alone) (OR 4.24, 95% CI 1.41 to 12.73, p=0.009), number of medications at admission (OR 1.32, 95% CI 1.09 to 1.59, p=0.002), and having coronary artery bypass graft surgery (OR 2.87, 95% CI 1.07 to 7.70, p=0.03) were associated with an increased risk for DRPs in the final model.

CONCLUSION: Hospital stay carries an increased risk for DRPs, especially at the postoperative stage. Modifiable risk factors for DRPs can be managed by required interventions performed by a multidisciplinary healthcare team.

PMID:36788008 | DOI:10.1136/ejhpharm-2022-003669

Reg Anesth Pain Med. 2023 Feb 14:rapm-2022-104166. doi: 10.1136/rapm-2022-104166. Online ahead of print.

ABSTRACT

INTRODUCTION: The ultrasound-guided interpectoral-pectoserratus plane block is a fascial plane block for superficial surgery of the anterolateral chest wall. This technique involves injecting a relatively large volume of local anesthetics (typically 30 mL of 0.25%-0.50%, ie, 75-150 mg ropivacaine) underneath the major and minor pectoral muscles of the anterior thoracic wall. There is a potential risk of toxic serum concentrations of local anesthetics due to systemic absorption.

METHODS: 22 patients scheduled for elective unilateral breast cancer surgery were included in this study. All surgery was performed with general anesthesia and an ultrasound-guided interpectoral-pectoserratus plane block with 2.5 mg/kg ropivacaine. Ten venous blood samples were collected at 0 (two samples) 10, 20, 30, 45, 60, 90 and 120 min and at 4 hours after performing the block. Free and total ropivacaine levels were measured at each time point. Albumin and alpha-1-acid-glycoprotein were measured to monitor shifts between the free and bound fraction of ropivacaine.

RESULTS: Samples of 20 patients were analyzed. The mean dose of ropivacaine was 172.8 (22.5) mg. In 50% of the patients, the potentially toxic threshold of 0.15 µg/mL free ropivacaine concentration was exceeded. Mean peak serum concentration occurred at 20 min postinjection.

CONCLUSIONS: This pharmacokinetic study demonstrated that a 2.5 mg/kg ropivacaine interpectoral-pectoserratus plane block may result in exceeding the threshold for local anesthetic systemic toxicity.

PMID:36787951 | DOI:10.1136/rapm-2022-104166

Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2205186120. doi: 10.1073/pnas.2205186120. Epub 2023 Feb 14.

ABSTRACT

Chemiluminescence (CL) with the elimination of excitation light and minimal autofluorescence interference has been wieldy applied in biosensing and bioimaging. However, the traditional emission of CL probes was mainly in the range of 400 to 650 nm, leading to undesired resolution and penetration in a biological object. Therefore, it was urgent to develop CL molecules in the near-infrared window [NIR, including NIR-I (650 to 900 nm) and near-infrared-II (900 to 1,700 nm)], coupled with unique advantages of long-time imaging, sensitive response, and high resolution at depths of millimeters. However, no NIR-II CL unimolecular probe has been reported until now. Herein, we developed an H2S-activated NIR-II CL probe [chemiluminiscence donor 950, (CD-950)] by covalently connecting two Schaap's dioxetane donors with high chemical energy to a NIR-II fluorophore acceptor candidate via intramolecular CL resonance energy transfer strategy, thereby achieving high efficiency of 95%. CD-950 exhibited superior capacity including long-duration imaging (~60 min), deeper tissue penetration (~10 mm), and specific H2S response under physiological conditions. More importantly, CD-950 showed detection capability for metformin-induced hepatotoxicity with 2.5-fold higher signal-to-background ratios than that of NIR-II fluorescence mode. The unimolecular NIR-II CL probe holds great potential for the evaluation of drug-induced side effects by tracking its metabolites in vivo, further facilitating the rational design of novel NIR-II CL-based detection platforms.

PMID:36787363 | DOI:10.1073/pnas.2205186120

Obes Surg. 2023 Feb 14. doi: 10.1007/s11695-023-06502-9. Online ahead of print.

ABSTRACT

PURPOSE: μ-receptor opioids are associated with unwanted gastrointestinal side effects and respiratory depression. A long-acting non-μ-receptor parenteral opioid is not currently available for management of acute and chronic postsurgical pain (CPSP). This double-blind clinical trial tested an extended-release κ-receptor agonist, sebacoyl dinalbuphine ester (SDE, Naldebain®) for management of surgical pain after laparoscopic bariatric surgery.

MATERIALS AND METHODS: Patients were randomly assigned to receive a single intramuscular injection of SDE (150 mg, n = 30) or vehicle solution (n = 30) at > 12 h before surgery. All patients received standard perioperative multimodal analgesia (MMA). The primary endpoint was the pain intensity in the beginning 7 days after operation. The secondary endpoints were adverse reactions up to 7 days and incidence of CPSP at 3 months after surgery.

RESULTS: Compared with placebos, the area under curves of visual analog scale (VAS) for 0-48 h after operation were significantly reduced in SDE group (143.3 ± 65.4 and 105.9 ± 36.3, P = 0.025). There were significantly fewer patients in the SDE group who had moderate-to-severe pain (VAS ≥ 4) (16.7% vs 50%; P = 0.012) at postoperative 48 h. Pain intensities were similar between the two groups at 72 h and 7 days postoperatively. The incidence of CPSP at 3 months was not different. SDE did not increase drug-related systemic adverse events.

CONCLUSION: In addition to the standard perioperative MMA, a single-dose injection of long-acting κ-receptor agonist SDE provides significantly better pain management for 48 h following laparoscopic bariatric surgery. A long-acting κ-receptor agonist opioid could improve in-hospital pain management and potentiate early discharge after operation without increasing drug-related systemic complications.

PMID:36787017 | DOI:10.1007/s11695-023-06502-9

Clin Infect Dis. 2023 Feb 14:ciad070. doi: 10.1093/cid/ciad070. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal duration of antimicrobial therapy for urinary tract infections in men remains controversial.

METHODS: To compare 7 days to 14 days total antibiotic treatment for febrile urinary tract infections in men, this multicenter randomized, double-blind placebo-controlled non-inferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile urinary tract infection and urine culture showing a single uropathogen.Participants were treated with ofloxacin or third generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14.The primary endpoint was treatment success, defined as a negative urine culture, the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent urinary tract infection within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales and drug-related events.

RESULTS: Two hundred and forty participants were randomly assigned to receive antibiotic therapy for 7 (115 participants) or 14 days (125 participants). In the ITT analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference-21.9 (-33.3 to -10.1)), demonstrating inferiority. Adverse events during antibiotic therapy were reported in four participants in the 7-day arm and seven in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups.

CONCLUSION: A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended.

PMID:36785526 | DOI:10.1093/cid/ciad070

J Pediatr Pharmacol Ther. 2023;28(1):78-83. doi: 10.5863/1551-6776-28.1.78. Epub 2023 Feb 3.

ABSTRACT

OBJECTIVE: Acetaminophen is a commonly administered analgesic and antipyretic medication that is generally well-tolerated. Recent studies in critically ill adults and subsets of pediatric patients with underlying cardiac disease identify an association between adverse hemodynamic effects with intravenous (IV) acetaminophen. However, the data may not be generalizable to a broader population of critically ill children. The objective of this study was to determine the incidence of hemodynamic changes associated with IV acetaminophen administration in critically ill pediatric medical-surgical patients.

METHODS: This was a retrospective observational study of all patients 18 years of age and younger who received at least 1 dose of IV acetaminophen in a pediatric intensive care unit at a quaternary care medical center, between July and December 2018. The primary outcome was the incidence of hypotension, defined as a decrease in mean arterial pressure (MAP) by at least 15% from baseline. Potential risk factors for IV acetaminophen-associated hypotension were assessed.

RESULTS: A total of 212 patients received 492 doses of IV acetaminophen. The primary endpoint of hypotension occurred following 24% of doses. An intervention for hypotension, primarily fluid resuscitation, was required for 11.9% of the dose-associated hypotension events. Patients receiving vasoactive infusions had more frequent dose-associated hypotension events than those not receiving infusions; however, no other potential risk factors were identified.

CONCLUSIONS: The incidence of hypotension observed in critically ill pediatric patients after IV acetaminophen administration is clinically relevant. Large placebo-controlled trial and further study of the risk factors and mechanism of this hemodynamic change are warranted.

PMID:36777989 | PMC:PMC9901319 | DOI:10.5863/1551-6776-28.1.78

Crohns Colitis 360. 2022 Mar 15;4(2):otac008. doi: 10.1093/crocol/otac008. eCollection 2022 Apr.

ABSTRACT

BACKGROUND: Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC.

METHODS: A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response.

RESULTS: Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment.

CONCLUSIONS: MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series.

PMID:36777041 | PMC:PMC9802423 | DOI:10.1093/crocol/otac008

Open Forum Infect Dis. 2023 Feb 8;10(2):ofad025. doi: 10.1093/ofid/ofad025. eCollection 2023 Feb.

NO ABSTRACT

PMID:36776775 | PMC:PMC9905358 | DOI:10.1093/ofid/ofad025

Medicina (B Aires). 2023;83(1):158-162.

ABSTRACT

Adverse reaction reporting is essential to understand the actual safety of marketed medicines. There are cases of patients with multidrug intolerance syndrome, an under-reported entity, which can occur when adverse reactions to more than two pharmacologically unrelated drugs occur in the same patient. We describe the case of a woman diagnosed with multisensitive Staphylococcus aureus endocarditis who experienced adverse reactions to five structurally unrelated antibiotics with different mechanisms of action in two consecutive hospitalisations. The reactions were secondary to cefazolin (tricytopenia), vancomycin (renal injury), daptomycin (elevated creatine phosphokinase) and linezolid (hepatotoxicity) in the first hospitalization, and to cotrimoxazole (thrombocytopenia) in the second. Transient damage to different organ systems was observed in all cases. Finally, hospital discharge was granted with clindamycin without further intercurrences until treatment was completed. This case could correspond to the aforementioned syndrome or to an as yet uncharacterized entity.

PMID:36774615

Eur J Pharmacol. 2023 Feb 10:175587. doi: 10.1016/j.ejphar.2023.175587. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Pharmacological treatments available for substance use disorder (SUD) focus on pharmacodynamics, agonizing or antagonizing the drug of abuse (DOA) on receptor level. Drawbacks of this approach include the reliance on long-term patient compliance, on-target off-site effects, perpetuation of addiction and unavailability for many DOAs. Newer, pharmacokinetic approaches are needed that restrict DOA's access to the brain or disrupt DOA-instated brain changes maintaining addiction. Biotechnology might be able to provide the right biopharmaceutical tools to deliver a fine-tuned solution with less side effects compared to currently available treatments.

METHODS: This review examines the available literature on biopharmaceuticals developed to treat SUD.

RESULTS: Active and passive immunization, metabolic enhancers that augment DOA metabolism and clearance, as well as genetic/epigenetic modulation are promising next generation SUD treatments. Active immunization relies on production of antidrug antibodies by means of vaccination, while passive immunization constitutes of exogenous administration of such antibodies. Metabolic enhancers include drug-specific metabolizing enzymes that can be administered or secreted by modified skin grafts, as well as catalytic antibodies that hasten DOA metabolism. Nanotechnological advances can also allow for brain delivery of siRNAs, mRNAs or DNA in order to modulate central, common in all addictions, genetic or epigenetic targets attenuating drug seeking behavior and reversing drug-induced brain changes.

CONCLUSIONS: and Scientific Significance: Biopharmaceuticals can in the future complement or even replace traditional pharmacodynamics approaches in SUD treatment. While passive and active immunization biopharmaceuticals have entered human clinical trials, metabolic enhancers and genetic approaches are at the preclinical level.

PMID:36775113 | DOI:10.1016/j.ejphar.2023.175587

Saudi Med J. 2023 Feb;44(2):194-201. doi: 10.15537/smj.2023.44.2.20220680.

ABSTRACT

OBJECTIVES: To assess the different side effects of COVID-19 vaccines at different scenarios in Saudi Arabia.

METHODS: This cross-sectional study sought to investigate the side effects of COVID-19 vaccines through an online survey of 2,718 participants in Saudi Arabia.

RESULTS: People can manage their expectations about vaccine side effects and deal with symptoms better by knowing beforehand that they are likely to experience mild side effects for a short period, symptoms that are manifested regardless of age, and infection before or after vaccination. There are certain uncommon side effects that affect more people who got infected, and not before vaccination; there are side effects that disproportionately impact women, and also the side effects that wane after the second dose.

CONCLUSION: These findings can assist in evaluating the concerns regarding vaccine acceptance. The public should be made aware that they are likely to experience at least one side effect, with temporary post-injection inflammation, musculoskeletal pain, fever, and headache as the most commonly reported side effects across the board. However, the common symptoms are mild to moderate, and the side effects last for a short period for most people.

PMID:36773975 | DOI:10.15537/smj.2023.44.2.20220680

Int J Mol Sci. 2023 Feb 3;24(3):3013. doi: 10.3390/ijms24033013.

ABSTRACT

Sphingolipids are exceptionally diverse, comprising hundreds of unique species. The bulk of circulating sphingolipids are synthesized in the liver, thereby plasma sphingolipid profiles represent reliable surrogates of hepatic sphingolipid metabolism and content. As changes in plasma sphingolipid content have been associated to exposure to drugs inducing hepatotoxicity both in vitro and in rodents, in the present study the translatability of the preclinical data was assessed by analyzing the plasma of patients with suspected drug-induced liver injury (DILI) and control subjects. DILI patients, whether intrinsic or idiosyncratic cases, had no alterations in total sphingoid base levels and profile composition compared to controls, whereby cardiovascular disease (CVD) was a confounding factor. Upon exclusion of CVD individuals, elevation of 1-deoxysphingosine (1-deoxySO) in the DILI group emerged. Notably, 1-deoxySO values did not correlate with ALT values. While 1-deoxySO was elevated in all DILI cases, only intrinsic DILI cases concomitantly displayed reduction of select shorter chain sphingoid bases. Significant perturbation of the sphingolipid metabolism observed in this small exploratory clinical study is discussed and put into context, in the consideration that sphingolipids might contribute to the onset and progression of DILI, and that circulating sphingoid bases may function as mechanistic markers to study DILI pathophysiology.

PMID:36769329 | PMC:PMC9917723 | DOI:10.3390/ijms24033013

Int J Mol Sci. 2023 Feb 3;24(3):2957. doi: 10.3390/ijms24032957.

ABSTRACT

SARS-CoV-2 is the virus that causes the infectious disease known as Corona Virus Disease 2019 (COVID-19). The severe impact of the virus on humans is undeniable, which is why effective vaccines were highly anticipated. As of 12 January 2022, nine vaccines have obtained Emergency Use Listing by the World Health Organization (WHO), and four of these are approved or authorized by the Centers for Disease Control and Prevention (CDC) in the United States. The initial clinical trials studying COVID-19 vaccine efficacy excluded pregnant and lactating individuals, meaning that data on the effects of the vaccine on breast milk were lacking. Until today, none of the authorized vaccines have been approved for use in individuals under six months. During the first months of life, babies do not produce their own antibodies; therefore, antibodies contained in their mothers' breastmilk are a critical protective mechanism. Several studies have shown the presence of SARS-CoV-2 antibodies in the breast milk of women who have been vaccinated or had been naturally infected. However, whether these are protective is still unclear. Additionally, research on the BNT162b2 mRNA vaccine developed by Pfizer-BioNTech and the mRNA-1273 vaccine developed by Moderna suggests that these vaccines do not release significant amounts, if any, of mRNA into breast milk. Hence, there is no evidence that vaccination of the mother poses any risk to the breastfed infant, while the antibodies present in breast milk may offer protection against the virus. The primary objective of this systematic review is to summarize the current understanding of the presence of immunoglobulins in human milk that are elicited by SARS-CoV-2 vaccines and to evaluate their ability to neutralize the virus. Additionally, we aim to quantify the side effects experienced by lactating mothers who have been vaccinated, as well as the potential for adverse effects in their infants. This study is critical because it can help inform decision-making by examining the current understanding of antibody secretion in breastmilk. This is particularly important because, although the virus tends to be less severe in younger individuals, infants who contract the disease are at a higher risk of requiring hospitalization compared to older children.

PMID:36769279 | PMC:PMC9917673 | DOI:10.3390/ijms24032957