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Lung Apr 2024Postoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery...
PURPOSE
Postoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery and post-surgical opioid administration on airway protection risk.
METHODS
Eight healthy adult cats were evaluated to determine changes in airway protection status and for evidence of dysphagia in two experiments. (1) In four female cats, airway protection status was tracked following routine abdominal surgery (spay surgery) plus low-dose opioid administration (buprenorphine 0.015 mg/kg, IM, q8-12 h; n = 5). (2) Using a cross-over design, four naive cats (2 male, 2 female) were treated with moderate-dose (0.02 mg/kg) or high-dose (0.04 mg/kg) buprenorphine (IM, q8-12 h; n = 5).
RESULTS
Airway protection was significantly affected in both experiments, but the most severe deficits occurred post-surgically as 75% of the animals exhibited silent aspiration.
CONCLUSION
Oropharyngeal swallow is impaired by the partial mu-opioid receptor agonist buprenorphine, most remarkably in the postoperative setting. These findings have implications for the prevention and management of aspiration pneumonia in vulnerable populations.
Topics: Animals; Cats; Female; Male; Analgesics, Opioid; Buprenorphine; Cat Diseases; Deglutition Disorders; Pneumonia; Cross-Over Studies
PubMed: 38538927
DOI: 10.1007/s00408-024-00672-8 -
The Pediatric Infectious Disease Journal Jun 2024The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13).
METHODS
This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12-15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions.
RESULTS
Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > -10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13.
CONCLUSION
A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.
Topics: Humans; Pneumococcal Vaccines; Infant; Double-Blind Method; Male; Female; Antibodies, Bacterial; Pneumococcal Infections; Immunoglobulin G; Streptococcus pneumoniae; Vaccines, Conjugate; Immunogenicity, Vaccine; United States; Serogroup; Healthy Volunteers
PubMed: 38535409
DOI: 10.1097/INF.0000000000004334 -
The Journal of Investigative Dermatology Mar 2024The read-through therapy suppresses premature termination codons and induces read-through activity consequently restoring missing proteins. Aminoglycosides are widely...
The read-through therapy suppresses premature termination codons and induces read-through activity consequently restoring missing proteins. Aminoglycosides are widely studied as read-through drugs in different human genetic disorders including hereditary skin diseases. Our previous work revealed that aminoglycosides have effect on COL17A1 nonsense mutations and represent a therapeutic option to alleviate disease severity. However, the amount of restored type XVII collagen (C17) in C17 deficient junctional epidermolysis bullosa (JEB-C17) keratinocytes was less than 1% relative to normal keratinocytes and was achieved only after high dose gentamicin treatment, which induced deep transcriptional changes. Therefore, in this study, we designed a strategy for the read-through therapy to challenge with aminoglycosides limitation factors in clinical use and the chronic inflammation in JEB-C17 patients. We developed TRID-C5 containing low dosage of aminoglycosides, CC-90009, NMDI-14, melatonin and apocynin that was able to induce about 20% of missing C17 without cell toxicity and effect on in vitro wound closure. TRID-C5 significantly induced COL17A1 expression and reverted the proinflammatory phenotype of JEB-C17 keratinocytes. Evaluation of this drug cocktail regarding its stability, penetration and efficacy as a topical treatment remains to be determined. TRID-C5 might represent an improved therapeutic strategy for JEB and for other genetic skin disorders.
PubMed: 38522573
DOI: 10.1016/j.jid.2024.02.027 -
Communications Medicine Mar 2024Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac...
BACKGROUND
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Currently, there are no approved treatments that address the underlying genetic cause of this disease, representing a significant unmet need. Mutations in Plakophilin-2 (PKP2), encoding a desmosomal protein, account for approximately 40% of ARVC cases and result in reduced gene expression.
METHODS
Our goal is to examine the feasibility and the efficacy of adeno-associated virus 9 (AAV9)-mediated restoration of PKP2 expression in a cardiac specific knock-out mouse model of Pkp2.
RESULTS
We show that a single dose of AAV9:PKP2 gene delivery prevents disease development before the onset of cardiomyopathy and attenuates disease progression after overt cardiomyopathy. Restoration of PKP2 expression leads to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, ameliorating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. RNA sequencing analyses show that restoration of PKP2 expression leads to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology.
CONCLUSIONS
We identify fundamental mechanisms of PKP2-associated ARVC beyond disruption of desmosome function. The observed PKP2 dose-function relationship indicates that cardiac-selective AAV9:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations.
PubMed: 38499690
DOI: 10.1038/s43856-024-00450-w -
Medicine Mar 2024A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk... (Review)
Review
RATIONALE
A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk of missing diagnosis and delayed treatment during the COVID-19 pandemic.
PATIENT CONCERN
A 60-year-old female patient developed anorexia, exhaustion, jaundice, nausea, and vomiting 10 days after COVID-19 infection. She was admitted to the Infectious Diseases Department because of recurring symptoms for more than a month.
DIAGNOSIS
Based on the patient's epidemiological history, clinical symptoms, and prior history, she was preliminarily diagnosed with GD induced by COVID-19 with severe hyperthyroid-related liver injury and chronic kidney disease stage 4. Drug-induced and radiation-induced liver injuries occurred sequentially throughout the therapy.
INTERVENTION
Methimazole (MMI) (10 mg/d) was administered for 1 week, and the patient's symptoms, thyroid function, and liver and kidney function improved. Nevertheless, the aforementioned symptoms and liver and kidney function deteriorated 20 days after increasing the MMI dose (20 mg/d). Therefore, in the presence of an artificial liver, hemodialysis, and other medical conditions, the treatment schedule was adjusted to individualized 131I anti-hyperthyroidism therapy.
OUTCOME
After 131I treatment, the patient's liver function returned to almost normal levels after a month, but worsened when the hepatoprotective drugs were stopped. Renal function did not deteriorate significantly and returned to baseline after 3 months. Thyroid function was restored to normal approximately 4 months later.
CONCLUSION
COVID-19 may induce GD. Multidisciplinary collaboration can be initiated as early as possible. Individualized 131I therapy or long-term low-dose MMI (10 mg/d) can be considered to manage hyperthyroidism in GD patients with liver and kidney dysfunction and to prolong liver protection therapy appropriately.
Topics: Female; Humans; Middle Aged; Iodine Radioisotopes; Pandemics; COVID-19; Graves Disease; Hyperthyroidism; Methimazole; Antithyroid Agents; Liver
PubMed: 38489722
DOI: 10.1097/MD.0000000000037456 -
Journal of Clinical Research in... Mar 2024Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported nonadherence rates in GH treatment have varied widely. Several factors may have...
OBJECTIVE
Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported nonadherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the COVID-19 pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated.
MATERIALS AND METHODS
This was a multicenter survey study that was sent to pediatric endocrinologists in pandemic period (June 2021-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, and missed dose data and the causes in the recent year (after the onset of the pandemic) were queried. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% nonadherence).
RESULTS
The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 mcg/kg, the annual growth rate was 1.15 SDS (min -2.74, max 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for nonadherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Nonadherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as nonadherence rate increased.
CONCLUSION
During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.
PubMed: 38488049
DOI: 10.4274/jcrpe.galenos.2024.2023-10-8 -
The Lancet Regional Health. Southeast... Mar 2024Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to...
BACKGROUND
Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to quantify the proportion of relapses observed at and beyond 6-months using the Infectious Diseases Data Observatory (IDDO) systematic review (SR) database.
METHODS
Studies in the IDDO SR database (1983-2021; 160 studies) were eligible for inclusion if follow-up was at least 6-months, relapse was clearly reported, and patients with HIV coinfections were excluded. Meta-analysis of single proportion was undertaken and the estimates were reported with 95% confidence intervals (CI).
FINDINGS
Overall, 131 studies enrolling 27,687 patients were included; 1193 patients relapsed. In the Indian sub-continent (ISC), relapse estimates at 6-months was 4.5% [95% CI: 2.6%-7.5%; = 66.2%] following single dose liposomal amphotericin B (L-AmB) and 1.5% [95% CI: 0.7%-3.3%; = 0%] for L-AmB in a combination therapy. In East Africa (EA), corresponding estimates were 3.8% [95% CI: 1.3%-10.9%; = 75.8%] following pentavalent antimony (PA), and 13.0% [95% CI: 4.3%-33.6%; = 0%] for PA + paromomycin. From 21 studies with follow-up longer than 6-months, 0.6% [95% CI: 0.2%-1.8%; = 0%] of patients relapsed after 6-months and estimated 27.6% [95% CI: 11.2%-53.4%; = 12%] of relapses would have been missed by a 6-month follow-up.
INTERPRETATION
The estimated relapse proportion ranged from 0.5% to 4.5% in ISC and 3.8%-13.0% in EA with the currently recommended drugs. Over one-quarter of relapses would be missed with 6-months follow-up suggesting a longer follow-up may be warranted.
FUNDING
Wellcome Trust (ref: 208378/Z/17/Z).
PubMed: 38482151
DOI: 10.1016/j.lansea.2023.100317 -
Cureus Feb 2024Background Infection in orthopedic surgery is one of the most dreaded complications. It is associated with prolonged morbidity, disability, and increased mortality. One...
Background Infection in orthopedic surgery is one of the most dreaded complications. It is associated with prolonged morbidity, disability, and increased mortality. One of the cornerstones of the prevention of infections is antibiotic prophylaxis. This study assessed the practice of antibiotic prophylaxis in arthroplasty surgeries in our local hospital. Methods One hundred and seventy-one elective joint replacement patients were retrospectively analyzed for documentation of antibiotic plan in postoperative instruction, choice of antibiotic, dose, and dosage. Compliance with the dosage (duration and frequency) of antibiotic prophylaxis was compared among patients who underwent different operations, among patients whose operation notes had antibiotics plans, and among those patients whose operation notes lacked this information. Results Ninety-six females and 75 males with a mean age of 71.4±9.8 years who underwent hip replacement, knee replacement, or shoulder replacement were included in this study. Preoperative and postoperative antibiotics were received by 100% and 94.7% of patients, respectively. In 19.3%, there was no instruction about postoperative antibiotics while 4% missed at least one postoperative dose. The dosage of postoperative prophylactic antibiotics was variable as 26.3% of the patients experienced delayed administration of doses. Not having intravenous access, failure to prescribe antibiotics, and prescribing antibiotics in the "once only" rather than "regular medication" section of the medication chart were the reasons for improper timing of antibiotic doses. Observing surgical safety checklist was effective in ensuring preoperative antibiotic administration, whereas failing to document antibiotic plan in operation note was associated with poor compliance with postoperative dosage. Interprofessional participation is crucial to compliance with antibiotic prophylaxis practice. Conclusion This study identified key areas for improvement in our antibiotics prophylaxis practice. It resulted in implementing strategies to improve staff's awareness about the importance of timely administration of prophylactic antibiotics and proper documentation by all team members.
PubMed: 38481888
DOI: 10.7759/cureus.54075 -
BMC Pediatrics Mar 2024Achieving universal health coverage includes ensuring that children have access to vaccines that are of high quality, safe, efficacious, and affordable. The Immunisation...
BACKGROUND
Achieving universal health coverage includes ensuring that children have access to vaccines that are of high quality, safe, efficacious, and affordable. The Immunisation Agenda 2030 aims to expand services to zero-dose and incompletely vaccinated children and reduce immunisation rate disparities as a contribution to vaccination equity. This study explored the factors influencing full vaccination status among children aged 12 - 23 months in a rural district of the Upper East Region of Ghana.
METHODS
A population-based cross-sectional study was conducted among carers of children aged 12 -23 months in the Kassena Nankana West district. A multistage sampling technique was used to select 360 carers. Information regarding the vaccination status of children was gathered through a combination of children's health record books and carers' recollections. Information on potential determinants was also systematically collected for analysis in Stata version 15.0.
RESULTS
The results showed that 76.9% (95% CI: 72.3 - 81.0) of children had full vaccinations per the national schedule. All children received at least one vaccination. A higher percentage of carers with incompletely vaccinated children reported that they had travelled with their children as the primary reason for missing certain vaccine doses. Full vaccination status was significantly associated with secondary (aOR = 2.60; 95% CI: 1.20-5.63) and tertiary (aOR = 3.98, 95% CI: 1.34-11.84) maternal educational level, being in a partnership relationship (aOR = 2.09, 95% CI: 1.03-4.25), and residing in close proximity to healthcare facilities (aOR = 0.41, 95% CI: 0.21-0.80).
CONCLUSIONS
Our study found that nearly one-quarter of children aged 12-23 months in the study setting are underserved with vaccination services for a variety of reasons. Effectively reaching these children will require strengthening health systems, including eliminating vaccine shortages, addressing the unique challenges faced by unmarried women with children aged 12-23 months, and improving accessibility to vaccination services.
Topics: Child; Humans; Female; Infant; Cross-Sectional Studies; Ghana; Vaccination; Vaccines; Immunization
PubMed: 38459467
DOI: 10.1186/s12887-024-04662-w -
The Pediatric Infectious Disease Journal Jun 2024Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains.
METHODS
This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events.
RESULTS
Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13.
CONCLUSIONS
PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.
Topics: Humans; Pneumococcal Vaccines; Infant; Double-Blind Method; Male; Female; Antibodies, Bacterial; Vaccines, Conjugate; Immunogenicity, Vaccine; Measles-Mumps-Rubella Vaccine; Pneumococcal Infections; Immunoglobulin G; Chickenpox Vaccine; Immunization Schedule; Streptococcus pneumoniae; Child, Preschool; Diphtheria-Tetanus-acellular Pertussis Vaccines; Vaccines, Combined
PubMed: 38456705
DOI: 10.1097/INF.0000000000004300