BMC Pharmacol Toxicol. 2024 Feb 1;25(1):13. doi: 10.1186/s40360-024-00738-6.

ABSTRACT

BACKGROUND: Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment and is highly effective with low-dose intermittent administration. MTX is occasionally used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP)/paracetamol for pain or inflammation control. With MTX treatment, the side effects, such as hepatotoxicity, renal failure, and myelosuppression should be considered. These are also seen with analgesics treatment.

METHODS: We used a large spontaneously reported adverse event database (FAERS [JAPIC AERS]) to analyze whether the reporting of adverse events increased upon MTX and analgesic therapy in patients with RA.

RESULTS: After identifying RA cases, the crude reporting odds ratios (cRORs) for hepatotoxicity, renal failure, and thrombocytopenia associated with the use of MTX, APAP, or NSAIDs were calculated by disproportionality analysis, which revealed significantly higher cRORs for these events. No analgesics showed consistent positive signals for drug-drug interaction (DDI) with concomitant low-dose MTX analyzed using four algorithms for DDI interaction (the Ω shrinkage measure, additive or multiplicative, and combination risk ratio models). However, in renal failure and thrombocytopenia, loxoprofen (Ω025 = 0.08) and piroxicam (Ω025 = 0.46), and ibuprofen (Ω025 = 0.74) and ketorolac (Ω025 = 3.52), respectively, showed positive signals in the Ω shrinkage measure model, and no consistency was found among adverse events or NSAIDs.

CONCLUSIONS: Studies using spontaneous reporting systems have limitations such as reporting bias or lack of patient background; however, the results of our comprehensive analysis support the results of previous clinical or epidemiological studies. This study also demonstrated the usefulness of FAERS for DDI assessment.

PMID:38303016 | PMC:PMC10832291 | DOI:10.1186/s40360-024-00738-6

BMC Geriatr. 2024 Feb 1;24(1):123. doi: 10.1186/s12877-024-04658-2.

ABSTRACT

BACKGROUND: Since 2003 when memantine was first approved for use in the management of moderate-severe Alzheimer's dementia, its use has become more widespread and is being explored in other diseases like neuropathic pain, epilepsy, and mood disorders. Our case uniquely highlights two important adverse effects in a patient who overdosed on memantine. One is hypertension, which is easy to overlook as a medication side effect. The other is echolalia which is the repetition of words and phrases spoken by another person. It is commonly seen in children with autism spectrum disorder and has been reported in older adults with head injuries, delirium, and neurocognitive disorders. The aim of this patient story is to highlight the importance of medication reconciliation with caregivers and knowledge of adverse drug reactions in patient management. This case report has been presented previously in the form of an abstract at the American Geriatrics Society Presidential poster session in May 2023.

CASE PRESENTATION: Our patient is an 86-year-old man with mild dementia and hypertension, who was brought to the emergency department (ED) due to abrupt onset of altered mental status and auditory hallucinations. Investigations including blood work, CT head and an electroencephalogram (EEG) did not reveal an etiology for this change in his condition. Due to elevated blood pressure on presentation, a nicardipine drip was started, and he was given IV midazolam to assist with obtaining imaging. While reviewing medications with his daughter, it was noted that sixty memantine pills were missing from the bottle. Poison control was contacted and they confirmed association of these features with memantine. With supportive care, his symptoms resolved in less than 100 h, consistent with the half-life of memantine. Notably, our patient was started on Memantine one month prior to this presentation.

CONCLUSIONS: Hypertensive urgency and echolalia were the most striking symptoms of our patient's presentation. Though hypertension is a known sign of memantine overdose, it can easily be contributed to medication non-compliance in patients with dementia, being treated for hypertension. According to our literature review, this the first case of memantine overdose presenting with echolalia, a sign that is not commonly associated with adverse reactions to medications. This highlights the importance of an early medication review, especially with caregivers of people with dementia.

PMID:38302876 | PMC:PMC10835811 | DOI:10.1186/s12877-024-04658-2

Sci Rep. 2024 Feb 1;14(1):2660. doi: 10.1038/s41598-024-52822-w.

ABSTRACT

This study aimed to detect signals of adverse drug reactions (ADRs) associated with biological disease-modifying antirheumatic drugs (DMARDs) and targeted therapies in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients. Utilizing the KOrean College of Rheumatology BIOlogics & Targeted Therapy Registry (KOBIO) data, we calculated relative risks, excluded previously reported drug-ADR pairs, and externally validated remaining pairs using US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and single centre's electronic health records (EHR) data. Analyzing data from 2279 RA and 1940 AS patients, we identified 35 significant drug-ADR pairs in RA and 26 in AS, previously unreported in drug labels. Among the novel drug-ADR pairs from KOBIO, 15 were also significant in the FAERS data. Additionally, 2 significant drug-laboratory abnormality pairs were found in RA using CDM MetaLAB analysis. Our findings contribute to the identification of 14 novel drug-ADR signals, expanding our understanding of potential adverse effects related to biological DMARDs and targeted therapies in RA and AS. These results emphasize the importance of ongoing pharmacovigilance for patient safety and optimal therapeutic interventions.

PMID:38302579 | PMC:PMC10834537 | DOI:10.1038/s41598-024-52822-w

Drug Ther Bull. 2024 Feb 1:dtb-2024-000008. doi: 10.1136/dtb.2024.000008. Online ahead of print.

NO ABSTRACT

PMID:38302286 | DOI:10.1136/dtb.2024.000008

Eur Heart J. 2024 Feb 1;45(5):317-320. doi: 10.1093/eurheartj/ehae026.

NO ABSTRACT

PMID:38302153 | DOI:10.1093/eurheartj/ehae026

Br J Hosp Med (Lond). 2024 Jan 2;85(1):1-2. doi: 10.12968/hmed.2023.0344. Epub 2024 Jan 17.

ABSTRACT

Adverse effects of perioperative opioids have led to the pursuit of 'opioid-free anaesthesia'. While early studies have shown that effective analgesia can be achieved without using opioids, with some reduction in unwanted effects, further research is needed to elucidate which patients may benefit most and how.

PMID:38300677 | DOI:10.12968/hmed.2023.0344

J Antimicrob Chemother. 2024 Jan 31:dkae009. doi: 10.1093/jac/dkae009. Online ahead of print.

ABSTRACT

OBJECTIVES: Amoxycillin/clavulanic acid is the most common antimicrobial cause of drug-induced liver injury in adults. It is a less common cause of severe drug-related hepatotoxicity in children despite its frequent use. We studied the incidence, characteristics and predictive factors for amoxycillin/clavulanic acid hepatoxicity in children.

DESIGN: Retrospective cohort study of children who received oral or intravenous amoxycillin/clavulanic acid at a quaternary children's hospital over a 5-year period. Children were included if they had liver function tests (LFTs) determined at baseline, during and within 3 months after the treatment course. Causality was assessed using the Naranjo criteria for adverse drug reactions and Roussel Uclaf Causality Assessment Method.

RESULTS: Of 3271 children prescribed amoxycillin/clavulanic acid, 374 were included. Forty-nine (13%) had LFT abnormalities related to amoxycillin/clavulanic acid. Fourteen (3.6%) fulfilled Common Terminology Criteria for Adverse Events (CTCAE) grade 2 criteria with clinically significant hepatotoxicity. Age <2 years, sepsis, post-gastrointestinal surgical indications, prolonged treatment course of >7 days and higher cumulative amoxycillin (>10 g) and clavulanic acid dose (>1 g) were predictive of hepatotoxicity. The median time to resolution of LFT abnormalities was 4 weeks (range 3-7).

CONCLUSIONS: The incidence of amoxycillin/clavulanic acid related LFT abnormalities (CTCAE Grade 2 or above) in children was 3.6%. A prolonged treatment course >7 days, high cumulative amoxycillin (10 g) and clavulanic acid (>1 g) doses, those aged <2 years, and patients with sepsis or post-gastrointestinal surgery were predictive of a higher likelihood of abnormal LFTs. LFT monitoring should be considered in children receiving ≥7 days of treatment, particularly in those with other predisposing factors.

PMID:38297994 | DOI:10.1093/jac/dkae009

Cureus. 2023 Dec 9;15(12):e50227. doi: 10.7759/cureus.50227. eCollection 2023 Dec.

ABSTRACT

This report describes the case of a 47-year-old woman with myalgias, weakness, and elevated creatine kinase associated with semaglutide therapy prescribed for weight loss. Her symptoms and laboratory markers were consistent with rhabdomyolysis and resolved after discontinuation of semaglutide. Upon rechallenge at a lower dose, symptoms recurred, and urinalysis was consistent with myoglobinuria. Symptoms again rapidly resolved upon discontinuation of the medication. It is imperative for physicians to recognize semaglutide as a possible cause of myalgias and rhabdomyolysis in clinically suspected patients. To the best of our knowledge, this is the first reported case in the literature and may be specific to semaglutide rather than a class effect of glucagon-like peptide 1 (GLP-1) agonists.

PMID:38192938 | PMC:PMC10773591 | DOI:10.7759/cureus.50227

BMC Womens Health. 2024 Jan 8;24(1):31. doi: 10.1186/s12905-023-02860-9.

ABSTRACT

BACKGROUND: Female genital mutilation has many sexual, physical, and psychological consequences. The present study aimed to examine the relationship between Female Genital Mutilation/Cutting (FGM/C), and Sexual Function among circumcised women in Sardasht City, Iran."

METHODS: In this present cross-sectional study, 197 women who were mutilated entered the study by simple random sampling from two healthcare centers in Sardasht, Iran. A gynecologist first performed a genital examination to identify the type of female genital mutilation of participants. Subsequently, Socio-demographic and FGM/C-related characteristics checklist and the female sexual function index questionnaire were completed by interview method. Data were analyzed using SPSS 23 software.

RESULTS: Type I and II of female genital mutilation were performed in 73.1 and 26.9% of the participants, respectively. The age range of performing female genital mutilation in type I and II of female genital mutilation was 4-10 years old in 67.4% and 71.1% respectively. Traditional practitioners/local women carried out the circumcision in all of the participants, and Sunnah/tradition was reported as the most common reason for doing this procedure. The average total score of FSFI index in type I and II of female genital mutilation was 23.5 ± 2.0 and 17.4 ± 2.39, respectively. In all domains of FSFI, women with type II of female genital mutilation obtained lower scores than women with type I.

CONCLUSION: Circumcised women have reduced scores in all domains of FSFI, and the severity of sexual dysfunction is related to the type of FGM/C. Considering the prevalence of female genital mutilation and its adverse effects, it is imperative to initiate cultural improvements through education and awareness. By educating and raising awareness among individuals about this issue, we can foster positive changes and address the problem effectively.

PMID:38191359 | PMC:PMC10775604 | DOI:10.1186/s12905-023-02860-9

J Int Med Res. 2024 Jan;52(1):3000605231220867. doi: 10.1177/03000605231220867.

ABSTRACT

Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing's syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients' circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.

PMID:38190848 | PMC:PMC10775748 | DOI:10.1177/03000605231220867

Home Healthc Now. 2024 Jan-Feb 01;42(1):6-12. doi: 10.1097/NHH.0000000000001223.

ABSTRACT

The prevalence of type 2 diabetes and obesity is increasing. Research has demonstrated the use of GLP-1 RA and SGLT-2i medications to be safe and effective for the long-term management of T2DM and obesity. As continued research supports the use of GLP-1 RA and SGLT-2i medications for additional indications, home care clinicians will increasingly care for patients on these medications. It is imperative that home care clinicians are aware of patient indications, adverse effects, and potential safety considerations related to these drugs to ensure patient goals are met.

PMID:38190158 | DOI:10.1097/NHH.0000000000001223

Cochrane Database Syst Rev. 2024 Jan 8;1:CD001552. doi: 10.1002/14651858.CD001552.pub3.

ABSTRACT

BACKGROUND: Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve at the wrist. Surgery is considered when symptoms persist despite the use of non-surgical treatments. It is unclear whether surgery produces a better outcome than non-surgical therapy. This is an update of a Cochrane review published in 2008.

OBJECTIVES: To assess the evidence regarding the benefits and harms of carpal tunnel release compared with non-surgical treatment in the short (< 3 months) and long (> 3 months) term.

SEARCH METHODS: In this update, we included studies from the previous version of this review and searched the Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, ClinicalTrials.gov and WHO ICTRP until 18 November 2022. We also checked the reference lists of included studies and relevant systematic reviews for studies.

SELECTION CRITERIA: We included randomised controlled trials comparing any surgical technique with any non-surgical therapies for CTS.

DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane.

MAIN RESULTS: The 14 included studies randomised 1231 participants (1293 wrists). Eighty-four per cent of participants were women. The mean age ranged from 32 to 53 years, and the mean duration of symptoms from 31 weeks to 3.5 years. Trial sizes varied from 22 to 176 participants. The studies compared surgery with: splinting, corticosteroid injection, splinting and corticosteroid injection, platelet-rich plasma injection, manual therapy, multimodal non-operative treatment, unspecified medical treatment and hand support, and surgery and corticosteroid injection with corticosteroid injection alone. Since surgery is generally used for its long-term effects, this abstract presents only long-term results for surgery versus splinting and surgery versus corticosteroid injection. 1) Surgery compared to splinting in the long term (> 3 months) Surgery probably results in a higher rate of clinical improvement (risk ratio (RR) 2.10, 95% confidence interval (CI) 1.04 to 4.24; 3 studies, 210 participants; moderate-certainty evidence). Surgery probably does not provide clinically important benefit in symptoms or hand function compared with splinting (moderate-certainty evidence). The mean Boston Carpal Tunnel Questionnaire (BCTQ) Symptom Severity Scale (scale 1 to 5; higher is worse; minimal clinically important difference (MCID) = 1) was 1.54 with splint and 0.26 points better with surgery (95% CI 0.52 better to 0.01 worse; 2 studies, 195 participants). The mean BCTQ Functional Status Scale (scale 1 to 5; higher is worse; MCID 0.7) was 1.75 with splint and 0.36 points better with surgery (95% CI 0.62 better to 0.09 better; 2 studies, 195 participants). None of the studies reported pain. Surgery may not provide better health-related quality of life compared with splinting (low-certainty evidence). The mean EQ-5D index (scale 0 to 1; higher is better; MCID 0.074) was 0.81 with splinting and 0.04 points better with surgery (95% CI 0.0 to 0.08 better; 1 study, 167 participants). We are uncertain about the risk of adverse effects (very low-certainty evidence). Adverse effects were reported amongst 60 of 98 participants (61%) in the surgery group and 46 of 112 participants (41%) in the splinting group (RR 2.11, 95% CI 0.37 to 12.12; 2 studies, 210 participants). Surgery probably reduces the risk of further surgery; 41 of 93 participants (44%) were referred to surgery in the splinting group and 0 of 83 participants (0%) repeated surgery in the surgery group (RR 0.03, 95% CI 0.00 to 0.21; 2 studies, 176 participants). This corresponds to a number needed to treat for an additional beneficial outcome (NNTB) of 2 (95% CI 1 to 9). 2) Surgery compared to corticosteroid injection in the long term (> 3 months) We are uncertain if clinical improvement or symptom relief differs between surgery and corticosteroid injection (very low-certainty evidence). The RR for clinical improvement was 1.23 (95% CI 0.73 to 2.06; 3 studies, 187 participants). For symptoms, the standardised mean difference (SMD) was -0.60 (95% CI -1.88 to 0.69; 2 studies, 118 participants). This translates to 0.4 points better (95% CI from 1.3 better to 0.5 worse) on the BCTQ Symptom Severity Scale. Hand function or pain probably do not differ between surgery and corticosteroid injection (moderate-certainty evidence). For function, the SMD was -0.12 (95% CI -0.80 to 0.56; 2 studies, 191 participants) translating to 0.10 points better (95% CI 0.66 better to 0.46 worse) on the BCTQ Functional Status Scale with surgery. Pain (0 to 100 scale) was 8 points with corticosteroid injection and 6 points better (95% CI 10.45 better to 1.55 better; 1 study, 123 participants) with surgery. We found no data to estimate the difference in health-related quality of life (very low-certainty evidence). We are uncertain about the risk of adverse effects and further surgery (very low-certainty evidence). Adverse effects were reported amongst 3 of 45 participants (7%) in the surgery group and 2 of 45 participants (4%) in the corticosteroid injection group (RR 1.49, 95% CI 0.25 to 8.70; 2 studies, 90 participants). In one study, 12 of 83 participants (15%) needed surgery in the corticosteroid group, and 7 of 80 participants (9%) needed repeated surgery in the surgery group (RR 0.61, 95% CI 0.25 to 1.46; 1 study, 163 participants).

AUTHORS' CONCLUSIONS: Currently, the efficacy of surgery in people with CTS is unclear. It is also unclear if the results can be applied to people who are not satisfied after trying various non-surgical options. Future studies should preferably blind participants from treatment allocation and randomise people who are dissatisfied after being treated non-surgically. The decision for a patient to opt for surgery should balance the small benefits and potential risks of surgery. Patients with severe symptoms, a high preference for clinical improvement and reluctance to adhere to non-surgical options, and who do not consider potential surgical risks and morbidity a burden, may choose surgery. On the other hand, those who have tolerable symptoms, who have not tried non-surgical options and who want to avoid surgery-related morbidity can start with non-surgical options and have surgery only if necessary. We are uncertain if the risk of adverse effects differs between surgery and non-surgical treatments. The severity of adverse effects may also be different.

PMID:38189479 | DOI:10.1002/14651858.CD001552.pub3

PeerJ. 2024 Jan 4;12:e16732. doi: 10.7717/peerj.16732. eCollection 2024.

ABSTRACT

OBJECTIVE: This study aims to assess and compare the potential of advanced nano/micro delivery systems, including quantum dots, carbon nanotubes, magnetic nanoparticles, dendrimers, and microneedles, as theranostic platforms for oral cancer. Furthermore, we seek to evaluate their respective advantages and disadvantages over the past decade.

MATERIALS AND METHODS: A comprehensive literature search was performed using Google Scholar and PubMed, with a focus on articles published between 2013 and 2023. Search queries included the specific advanced delivery system as the primary term, followed by oral cancer as the secondary term (e.g., "quantum dots AND oral cancer," etc.).

RESULTS: The advanced delivery platforms exhibited notable diagnostic and therapeutic advantages when compared to conventional techniques or control groups. These benefits encompassed improved tumor detection and visualization, enhanced precision in targeting tumors with reduced harm to neighboring tissues, and improved drug solubility and distribution, leading to enhanced drug absorption and tumor uptake.

CONCLUSION: The findings suggest that advanced nano/micro delivery platforms hold promise for addressing numerous challenges associated with chemotherapy. By enabling precise targeting of cancerous cells, these platforms have the potential to mitigate adverse effects on surrounding healthy tissues, thus encouraging the development of innovative diagnostic and therapeutic strategies for oral cancer.

PMID:38188167 | PMC:PMC10771769 | DOI:10.7717/peerj.16732

Zhonghua Yu Fang Yi Xue Za Zhi. 2023 Dec 6;57(12):2002-2009. doi: 10.3760/cma.j.cn112150-20230105-00011.

ABSTRACT

To review and investigate the diagnosis results of local anesthetics (LA) allergy and improve the understanding of LA allergy in clinician. From March 2017 to February 2022, a total of 24 patients were investigated in Allergy Center of West China Hospital,Sichuan University on suspicion of LA allergy. Clinical data and results of skin tests and drug provocation tests (DPT) with the suspected drugs were retrospectively evaluated. The value of standardized diagnostic protocol in the LA allergy were analyzed. The results showed that 24 patients (3 men/21 women) were included with age range from 20 to 74 years. Three cases (12.5%) were positive in previous LA skin tests and proved to be tolerated through standardized tests. Twenty-one patients were initially diagnosed as "LA allergy" because of adverse reactions after previous use of LA, including 20 cases of immediate-type reaction and 1 case of delayed-type reaction. Three cases were considered LA allergy through standardized diagnosis approaches, including skin tests and DPT. One patient was diagnosed with anaphylaxis caused by chlorhexidine. Of the remaining 17 patients, 7 were considered as psychosomatic reactions (29.1%), 3 of sympathetic nervous system conditions (12.5%), 1 of spontaneous urticaria (4.2%), 2 of vasovagal syncope (8.3%), drug side effects (8.3%), skin irritation (8.3%), respectively. In conclusion, true allergic reactions to LA are rare. Through standardized skin tests and DPT, allergy can be ruled out in the vast majority of patients who complain of "LA allergy". For patients who are highly suspected of LA inducing anaphylaxis, other local anesthetics that can be used as safe alternatives should be determined by diagnostic tests according to future needs.

PMID:38186148 | DOI:10.3760/cma.j.cn112150-20230105-00011

Pediatr Infect Dis J. 2024 Jan 4. doi: 10.1097/INF.0000000000004243. Online ahead of print.

ABSTRACT

BACKGROUND: Study of liquid lopinavir/ritonavir (LPV/r) in young infants has been limited by concerns for its safety in neonates.

METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1106 was a phase IV, prospective, trial evaluating the safety and pharmacokinetics of antiretroviral medications administered according to local guidelines to South African preterm and term infants <3 months of age. Safety evaluation through 24-week follow-up included clinical, cardiac and laboratory assessments. Pharmacokinetic data from P1106 were combined with data from International Maternal Pediatric Adolescent AIDS Clinical Trials Network studies P1030 and P1083 in a population pharmacokinetics model used to simulate LPV exposures with a weight-band dosing regimen in infants through age 6 months.

RESULTS: Safety and pharmacokinetics results were similar in 13/28 (46%) infants initiating LPV/r <42 weeks postmenstrual age (PMA) and in those starting ≥42 weeks PMA. LPV/r was started at a median (range) age of 47 (13-121) days. No grade 3 or higher adverse events were considered treatment related. Modeling and simulation predicted that for infants with gestational age ≥27 weeks who receive the weight-band dosing regimen, 82.6% will achieve LPV trough concentration above the target trough concentration of 1.0 µg/mL and 56.6% would exceed the observed adult lower limit of LPV exposure of 55.9 µg·h/mL through age 6 months.

CONCLUSIONS: LPV/r oral solution was safely initiated in a relatively small sample size of infants ≥34 weeks PMA and >2 weeks of life. No serious drug-related safety signal was observed; however, adrenal function assessments were not performed. Weight-band dosing regimen in infants with gestational age ≥27 weeks is predicted to result in LPV exposures equivalent to those observed in other pediatric studies.

PMID:38190642 | DOI:10.1097/INF.0000000000004243

Front Med (Lausanne). 2023 Dec 21;10:1304369. doi: 10.3389/fmed.2023.1304369. eCollection 2023.

ABSTRACT

BACKGROUND: Gram-negative bacteria is a global public health problem. Treatment options include novel beta-lactamase inhibitors.

OBJECTIVES: The objective of this study was to collect information on the efficacy and safety of novel β-lactamase inhibitor combinations such as imipenem-cilastatin/relebactam (IMI/REL).

METHODS: In order to comprehensively evaluate the clinical, microbiological, and adverse events outcomes, a meta-analysis was conducted on clinical trials comparing novel β-lactamase inhibitor combinations with existing comparator therapies.

RESULTS: Four studies comprising 948 patients were included in the analysis. IMI/REL therapy demonstrated similar clinical responses to comparators across various treatment visits, including discontinuation of intravenously administered therapy visits [DCIV, RR = 1.00 (0.88, 1.12)], early follow-up visits [EFU, RR = 1.00 (0.89, 1.14)], late follow-up visits [LFU, RR = 1.00 (0.88, 1.13)]. Moreover, no significant difference in the microbiologic response of MITT patients was observed between IMI/REL and comparators across DCIV [RR = 0.99 (0.89, 1.11)], EFU [RR = 1.01 (0.95, 1.07)], and LFU visits [RR = 1.00 (90.94, 1.07)]. In terms of safety, therapy with IMI/REL and comparators exhibited similar risks of at least one adverse event (AE), drug-related AEs, and discontinuation due to AEs. The incidence of serious AEs (SAEs) was significantly lower in the IMI/REL group compared to the comparison groups. The predominant AEs were gastrointestinal disorders, with no significant difference observed between the IMI/REL group and comparators.

CONCLUSION: The clinical and microbiologic response to IMI/REL in the treatment of bacterial infection was comparable to that of the comparator. Furthermore, the incidence of AEs and the tolerability of IMI/REL were similar among the comparators. Based on these findings, IMI/REL can be considered as a viable alternative treatment option.

PMID:38188339 | PMC:PMC10767998 | DOI:10.3389/fmed.2023.1304369

Hosp Pediatr. 2024 Jan 8:e2023007265. doi: 10.1542/hpeds.2023-007265. Online ahead of print.

ABSTRACT

OBJECTIVES: Hospital at home (HAH) replaces acute inpatient hospital care for selected patients by providing care in their homes. We sought to describe the characteristics, management, and complications of patients with osteoarticular infections (OAIs) treated in an HAH program and its economic impact.

METHODS: We conducted a retrospective observational study evaluating an HAH program in a pediatric hospital in Spain, describing the characteristics of patients with confirmed OAIs requiring intravenous antibiotic therapy admitted to this program between January 2019 and December 2022. The program operates as a virtual ward with possible daily visits by physicians and nurses and 24/7 telephone contact.

RESULTS: A total of 88 patients (median age, 4.1 years; interquartile range [IQR], 1.7-10.6) with OIAs were admitted to the HAH program. Osteomyelitis (57%) and septic arthritis (29%) were the most frequent infections. Cefuroxime (42%) and cefazolin (39%) were the most frequently prescribed antibiotics. Caregiver self-administration was performed in 99%, allowing multiple daily doses of antimicrobial therapy, 80% by peripheral line. Thirteen patients (15%) had drug-related adverse events, only 3 requiring drug modification. Two patients (2%) were readmitted during HAH, and 1 was readmitted within 30 days of HAH discharge. The median HAH stay was 7 days (IQR, 4-8.75). For osteomyelitis, hospital days lowered from 8.5 days (IQR, 4.5-12) to 4 days (IQR, 3-7) after HAH implementation (P = .005) with 68% per-patient estimated cost savings.

CONCLUSIONS: HAH treatment of OAIs is effective and cost-efficient. Patient support by medical and nursing staff, adequate family training, and regular communication are essential to ensure safe home admission.

PMID:38186289 | DOI:10.1542/hpeds.2023-007265

Sci Rep. 2024 Jan 5;14(1):620. doi: 10.1038/s41598-024-51302-5.

ABSTRACT

Salinity stress has detrimental effects on various aspects of plant development. However, our understanding of strategies to mitigate these effects in crop plants remains limited. Recent research has shed light on the potential of sodium acetate as a mitigating component against salinity stress in several plant species. Here, we show the role of acetate sodium in counteracting the adverse effects on oat (Avena sativa) plants subjected to NaCl-induced salinity stress, including its impact on plant morphology, photosynthetic parameters, and gene expression related to photosynthesis and antioxidant capacity, ultimately leading to osmoprotection. The five-week experiment involved subjecting oat plants to four different conditions: water, salt (NaCl), sodium acetate, and a combination of salt and sodium acetate. The presence of NaCl significantly inhibited plant growth and root elongation, disrupted chlorophylls and carotenoids content, impaired chlorophyll fluorescence, and down-regulated genes associated with the plant antioxidant defense system. Furthermore, our findings reveal that when stressed plants were treated with sodium acetate, it partially reversed these adverse effects across all analyzed parameters. This reversal was particularly evident in the increased content of proline, thereby ensuring osmoprotection for oat plants, even under stressful conditions. These results provide compelling evidence regarding the positive impact of sodium acetate on various plant development parameters, with a particular focus on the enhancement of photosynthetic activity.

PMID:38182773 | PMC:PMC10770181 | DOI:10.1038/s41598-024-51302-5

Sci Rep. 2024 Jan 5;14(1):591. doi: 10.1038/s41598-023-48640-1.

ABSTRACT

Proton pump inhibitors (PPIs) are commonly used in cancer patients, but their impact on treatment outcomes in multiple myeloma (MM) patients remains unclear. This study investigated the association of PPI use with survival and adverse effects in MM patients across three randomized-control trials initiating daratumumab, lenalidomide, or bortezomib combination treatments. Cox proportional hazard analysis and logistic regression were employed to assess the associations with treatment outcomes, while adjusting for age, sex, weight, MM international staging system stage, ECOG-performance status, comorbidity count, and presence of gastrointestinal disorders. Pooled data involving 1804 patients revealed that 557 (32%) used PPIs at baseline. PPI use was independently associated with worse overall survival (adjusted HR [95% CI] 1.32 [1.08-1.62], P = 0.007) and grade ≥ 3 adverse events (adjusted OR [95% CI] 1.39 [1.03-1.88], P = 0.030). However, the association with progression-free survival did not reach statistical significance (adjusted HR [95% CI] 1.14 [0.97-1.33], P = 0.112). Findings were consistent across trials and treatment arms. PPI use was identified as a negative prognostic factor in MM patients, potentially enhancing clinical decisions regarding its use. Further research is needed to fully comprehend the impacts and safety of PPI use in MM patients.

PMID:38182614 | PMC:PMC10770405 | DOI:10.1038/s41598-023-48640-1

PLoS One. 2024 Jan 5;19(1):e0296384. doi: 10.1371/journal.pone.0296384. eCollection 2024.

ABSTRACT

PURPOSE: Metastatic breast cancer [MBC] is the leading cause of cancer death in women globally with no cure. Women diagnosed with MBC endure a catastrophic upheaval to multiple aspects of their life and a radically transformed future landscape. Evidence suggests that the provision of care for women living with metastatic breast cancer is inadequate, socially isolating and stigmatising. To date, this topic has received little research attention. To increase understanding of the experiences of women living with MBC, a synthesis of current evidence is required. This paper presents a review of qualitative evidence on women's experiences of MBC.

METHODS: A qualitative evidence synthesis [QES] was conducted to synthesise primary qualitative research on the experiences of women living with MBC. Searches were performed of electronic databases Medline, Medline Ovid, PsycINFO, Psych articles, PubMED, CINAHL Complete, Scopus and grey literature databases. The methodological quality of the included studies was appraised using a modified version of the Critical Appraisal Skills Programme [CASP]. Title, abstract, and full-text screening were undertaken. A 'best fit' framework approach using the ARC [Adversity, Restoration, Compatibility] framework was used to guide data extraction and synthesis. Confidence in the findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation, Confidence in the Evidence from Reviews of Qualitative research [GRADE-CERQual].

RESULTS: 28 papers from 21 research studies containing 478 women's experiences of living with MBC were deemed suitable for inclusion in this qualitative evidence synthesis. Findings are presented in a new conceptual framework RAAW [adapted from ARC] for women living with MBC under themes: Reality, Adversity, Adjustment and Wellbeing. Findings revealed that a diagnosis of MBC impacted every aspect of women's lives; this is different to a diagnosis of early breast cancer. An overarching theme of lack of support extended across various facets of their lives. A lack of psychological, emotional, and psychosocial support was evident, with a critical finding that models of care were not fit for purpose. Deficits included a lack of information, knowledge, inclusion in shared decision-making and MDT support, specifically the need for palliative care/oncology support access. Some women living with MBC wanted to be identified as having a chronic illness not a life-limiting illness. Culture and socioeconomic standing influenced the availability of various types of support. The impact of treatment and symptoms had an adverse effect on women's quality of life and affected their ability to adjust.

CONCLUSION: This review synthesised the qualitative literature on the experiences of women living with MBC. The ARC framework used in the synthesis was adapted to develop a revised conceptual framework titled RAAW to represent the evidence from this review on experiences for women living with MBC; Reality & Adversity: A diagnosis of MBC; Adjustment: Living with MBC; Wellbeing: Awareness, meaning, engagement [RAAW; MBC].

PMID:38181009 | PMC:PMC10769043 | DOI:10.1371/journal.pone.0296384