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A longitudinal study of naloxone opioid overdose awareness and reversal training for first-year medical students: specific elements require reinforcement

Harm Reduct J. 2022 Jul 2;19(1):70. doi: 10.1186/s12954-022-00656-y.

ABSTRACT

BACKGROUND: The opioid epidemic is a progressively worsening public health crisis that continues to impact healthcare system strategies such as overdose reversal and destigmatization. Even among healthcare professionals, there remains a lack of confidence in naloxone administration and a prevalence of stigma. While training can play a major impact in reducing these shortcomings, the long-term effectiveness has yet to be characterized in training healthcare professionals. This study examined the long-term retention of opioid overdose awareness and reversal training (OOART) by evaluating performance at two-time intervals, immediately post-training and at a 3-month follow-up.

METHODS: Voluntary training was offered to first-year (M1) medical students at the Drexel University College of Medicine in 2021. At this training, 118 students completed training, 95 completed the post-training survey, and 42 completed the 3-month follow-up.

RESULTS: Opioid reversal knowledge questions assessed significantly increased scores post-training and at the 3-month follow-up. In three of the attitude questions, scores were improved at both follow-up timepoints. In addition, three attitude questions indicating a participant’s confidence to respond to an opioid overdose situation increased directly after the training, but regressed at the 3-month follow-up. The remaining questions did not show any statistical difference across the survey intervals.

CONCLUSIONS: This study establishes that while OOART provides participants with the knowledge of how to respond to an opioid overdose, the retention of this knowledge at a 3-month interval is reduced. The results were mixed for longitudinal assessment of participant’s attitudes toward people with opioid use disorder. Some positive increases in attitudes were retained at the 3-month interval, while others trended back toward pre-training levels. These results support the effectiveness of the training but also provide evidence that OOART must be reinforced often.

PMID:35780103 | DOI:10.1186/s12954-022-00656-y

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dbBIP: a comprehensive bipolar disorder database for genetic research

Database (Oxford). 2022 Jul 2;2022:baac049. doi: 10.1093/database/baac049.

ABSTRACT

Bipolar disorder (BIP) is one of the most common hereditary psychiatric disorders worldwide. Elucidating the genetic basis of BIP will play a pivotal role in mechanistic delineation. Genome-wide association studies (GWAS) have successfully reported multiple susceptibility loci conferring BIP risk, thus providing insight into the effects of its underlying pathobiology. However, difficulties remain in the extrication of important and biologically relevant data from genetic discoveries related to psychiatric disorders such as BIP. There is an urgent need for an integrated and comprehensive online database with unified access to genetic and multi-omics data for in-depth data mining. Here, we developed the dbBIP, a database for BIP genetic research based on published data. The dbBIP consists of several modules, i.e.: (i) single nucleotide polymorphism (SNP) module, containing large-scale GWAS genetic summary statistics and functional annotation information relevant to risk variants; (ii) gene module, containing BIP-related candidate risk genes from various sources and (iii) analysis module, providing a simple and user-friendly interface to analyze one’s own data. We also conducted extensive analyses, including functional SNP annotation, integration (including summary-data-based Mendelian randomization and transcriptome-wide association studies), co-expression, gene expression, tissue expression, protein-protein interaction and brain expression quantitative trait loci analyses, thus shedding light on the genetic causes of BIP. Finally, we developed a graphical browser with powerful search tools to facilitate data navigation and access. The dbBIP provides a comprehensive resource for BIP genetic research as well as an integrated analysis platform for researchers and can be accessed online at http://dbbip.xialab.info. Database URL: http://dbbip.xialab.info.

PMID:35779245 | DOI:10.1093/database/baac049

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A new multiphase calcium phosphate graft material improves bone healing-An in vitro and in vivo analysis

J Biomed Mater Res B Appl Biomater. 2022 Jul 2. doi: 10.1002/jbm.b.35121. Online ahead of print.

ABSTRACT

This study aims to evaluate the potential of a novel biomaterial synthesized from amorphous calcium phosphate (ACP), octacalcium phosphate (OCP), and hydroxyapatite (HA) to repair critical-sized defects (CSD) in rabbit calvaria. In vitro analyses of cell viability, cell proliferation, formation of mineral nodules, and cell differentiation using qPCR were performed for comparing experimental calcium phosphate (ECP), deproteinized bovine bone (DBB), and beta-tricalcium phosphate (β-TCP). Bilateral CSDs were created in 45 rabbit calvaria. Six groups were evaluated: ECP, ECP + fibrin sealant (ECP + S), coagulum, autogenous bone, DBB, and β-TCP. Euthanasia was performed at 2, 4, and 8 weeks, followed by micro-computed tomography and histological and immunohistochemical analyses. Results from in vitro analyses revealed similar biocompatibility for all tested materials and a tendency for higher gene expression of some bone markers in the ECP group than in β-TCP and DBB groups at 7 days. In contrast to that in DBB and β-TCP groups, ECP displayed growing bone volume over total volume percentage (BV/TV%) with time in vivo. Histological analysis revealed a greater number of giant cells and reduced size of grafted particles in ECP during all periods of analysis. RUNX-2 expression was statistically lower in ECP than DBB at 2 and 4 weeks. Despite no statistical significance, ECP presented the highest absolute values for ALP-expression at 2, 4, and 8 weeks compared with other groups. Together, our findings indicate that a combination of the ACP, OCP, and HA phases into ECP is beneficial and promising for bone regeneration.

PMID:35779277 | DOI:10.1002/jbm.b.35121

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Psychological complications in patients with acromegaly: relationships with sex, arthropathy, and quality of life

Endocrine. 2022 Jul 2. doi: 10.1007/s12020-022-03106-8. Online ahead of print.

ABSTRACT

PURPOSE: Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients’ quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL.

METHODS: One hundred and seventy-one acromegalic patients (95 women and 76 men, aged 20-85 years) among those recruited in a cross-sectional Italian multicentric study were investigated. Each patient filled in three validated questionnaires: AcroQoL, WOMAC (measuring articular pain, stiffness and functionality), and AIMS (evaluating articular symptoms and depression).

RESULTS: A very high (up to 28%) depression rate was detected in acromegalic subjects. Two patients showing pathological AIMS depression scores, committed suicide during the three years observational period. In our population poor psychological status was significantly associated with female sex. Furthermore, a significant strong correlation was found between AIMS depression score and WOMAC score. Both depression and arthropathy-related motor disability turned out to independently contribute with similar strength to the impairment of QoL.

CONCLUSIONS: We report a high prevalence of depression in acromegaly, which is associated with female sex and arthropathy. Both depression and arthropathy strongly and independently contribute to the impaired QoL of patients. Our study shows that assessment and monitoring of psychological status is mandatory in acromegaly, also suggesting an inexpensive tool for this assessment.

PMID:35779206 | DOI:10.1007/s12020-022-03106-8

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Risk Factors of Pneumonia in Primary Antibody Deficiency Patients Receiving Immunoglobulin Therapy: Data from the US Immunodeficiency Network (USIDNET)

J Clin Immunol. 2022 Jul 2. doi: 10.1007/s10875-022-01317-2. Online ahead of print.

ABSTRACT

BACKGROUND: Despite immunoglobulin replacement (IgRT) therapy, some patients with primary antibody deficiency (PAD) continue to develop respiratory infections. Recurrent and severe respiratory infections, particularly pneumonia, can lead to significant morbidity and mortality. Therefore, we sought to determine the risk factors of developing pneumonia in PAD patients, already receiving IgRT.

METHODS: We evaluated clinical and laboratory features of PAD patients enrolled in the US Immune Deficiency Network (USIDNET) registry by April 2017. Patients were included if they met the following criteria: (1) PAD diagnosis (common variable immunodeficiency (CVID), agammaglobulinemia, hypogammaglobinemia, and specific antibody deficiency (SAD) and (2) available data on infections before and after IgRT. Patients were excluded if they were not receiving IgRT, or if no pre/post infections data were available. Descriptive and multivariable logistic regression analyses were used to identify factors associated with pneumonia post-IgRT.

RESULTS: A total of 1232 patients met the inclusion criteria. Following IgRT, 218 patients (17.7%) were reported to have at least one pneumonia episode. Using multivariate logistic regression analysis, we found a statistically significant increased risk of pneumonia in patients with asthma (OR: 2.55, 95% CI (1.69-3.85), p < 0.001) bronchiectasis (OR: 3.94, 95% CI (2.29-6.80), p < 0.001), interstitial lung disease (ILD) (OR: 3.28, 95%CI (1.43-7.56), p < 0.005), splenomegaly (OR: 2.02, 95%CI (1.08-3.76), p < 0.027), allergies (OR: 2.44, 95% CI [1.44-4.13], p = 0.001), and patients who were not on immunosuppressives (OR: 1.61; 95%CI [1.06-2.46]; p = 0.027). For every 50 unit increase in IgA, the odds of reporting pneumonia post IgRT decreased (OR: 0.86, 95% CI [0.73-1.02], p = 0.062). Infectious organisms were reported in 35 of 218 patients who reported pneumonia after IgRT. Haemophilus influenzae was the most frequently reported (n = 11, 31.43%), followed by Streptococcus pneumoniae (n = 7, 20.00%).

CONCLUSION: Our findings suggest PAD patients with chronic and structural lung disease, splenomegaly, and allergies were associated with persistent pneumonia. However, our study is limited by the cross-sectional nature of the USIDNET database and limited longitudinal data. Further studies are warranted to identify susceptible causes and explore targeted solutions for prevention and associated morbidity and mortality.

CLINICAL IMPLICATIONS: Patients with primary antibody deficiency with structural lung disease, allergies, and splenomegaly are associated with persistent pneumonia post-IgRT.

PMID:35779201 | DOI:10.1007/s10875-022-01317-2

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Safety, Tolerability, Pharmacokinetics and Initial Pharmacodynamics of a Subcommissural Organ-Spondin-Derived Peptide: A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose First-in-Human Study

Neurol Ther. 2022 Jul 2. doi: 10.1007/s40120-022-00380-6. Online ahead of print.

ABSTRACT

INTRODUCTION: This randomized, double-blind, placebo-controlled study in healthy volunteers assessed the safety, tolerability, and pharmacokinetics of single ascending doses of intravenously administered NX210-a linear peptide derived from subcommissural organ-spondin-and explored the effects on blood/urine biomarkers and cerebral activity.

METHODS: Participants in five cohorts (n = 8 each) were randomized to receive a single intravenous dose of NX210 (n = 6 each) (0.4, 1.25, 2.5, 5, and 10 mg/kg) or placebo (n = 2 each); in total, 10 and 29 participants received placebo and NX210, respectively. Blood samples were collected for pharmacokinetics within 180 min post dosing. Plasma and urine were collected from participants (cohorts: 2.5, 5, and 10 mg/kg) for biomarker analysis and electroencephalography (EEG) recordings within 48 h post dosing. Safety/tolerability and pharmacokinetic data were assessed before ascending to the next dose.

RESULTS: The study included 39 participants. All dosages were safe and well tolerated. All treatment-emergent adverse events (n = 17) were of mild severity and resolved spontaneously (except one with unknown outcome). Twelve treatment-emergent adverse events (70.6%) were deemed drug related; seven of those (58.3%) concerned nervous system disorders (dizziness, headache, and somnolence). The pharmacokinetic analysis indicated a short half-life in plasma (6-20 min), high apparent volume of distribution (1870-4120 L), and rapid clearance (7440-16,400 L/h). In plasma, tryptophan and homocysteine showed dose-related increase and decrease, respectively. No drug dose effect was found for the glutamate or glutamine plasma biomarkers. Nevertheless, decreased blood glutamate and increased glutamine were observed in participants treated with NX210 versus placebo. EEG showed a statistically significant decrease in beta and gamma bands and a dose-dependent increasing trend in alpha bands. Pharmacodynamics effects were sustained for several hours (plasma) or 48 h (urine and EEG).

CONCLUSION: NX210 is safe and well tolerated and may exert beneficial effects on the central nervous system, particularly in terms of cognitive processing.

PMID:35779189 | DOI:10.1007/s40120-022-00380-6

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Downstream Process Development for Extraction of Prodigiosin: Statistical Optimization, Kinetics, and Biochemical Characterization

Appl Biochem Biotechnol. 2022 Jul 2. doi: 10.1007/s12010-022-04053-w. Online ahead of print.

ABSTRACT

Prodigiosin is natural red colourant derived from Serratia marcescens. However, the high cost of prodigiosin restricts its use in food and pharmaceutical industries, which can be addressed with the design of a suitable extraction procedure. Therefore, the present study aims to use Taguchi methodology to optimize various process parameters during ultrasound-assisted extraction (UAE) to get a higher prodigiosin extraction yield. The most significant contribution comes from the solid-to-liquid ratio (36.66%), followed by sonication of duty cycle (34.82%), medium pH (15.7%), and acoustic intensity (12.82%). The Taguchi technique predicts the highest optimal yield using the solid-liquid ratio (0.3 g/mL), duty cycle sonication (75%), acoustic intensity (12.5 w/cm2), and medium pH (3) as parameters. When the extraction conditions were optimized, the yield of prodigiosin increased by 4166.89 mg/L. In the future, the above extraction conditions determined using Taguchi approach will be applied for large-scale extraction of prodigiosin. Finally, a second-order kinetic model is used to suit the batch extraction investigation and the second-order rate constant (k) has a value of 4 × 10-5 L/mg/min. In the future, the rate constant, which is reported for the first time, will be used to create a batch extractor for commercial extraction of prodigiosin. Prodigiosin has also been shown to have substantial antioxidant and scavenging properties, which increase in a dose-dependent way with prodigiosin concentration. Because of its antioxidant and scavenging properties, prodigiosin can be used as food additives or pharmaceutical ingredients in industries.

PMID:35779175 | DOI:10.1007/s12010-022-04053-w

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Publication activity in water treatments: Web of Science-based bibliometric analysis of the last two decades

Int J Biometeorol. 2022 Jul 2. doi: 10.1007/s00484-022-02323-0. Online ahead of print.

ABSTRACT

We evaluated the quantity and quality of scientific publications linked with water treatments using the Web of Science (WoS) database. The WoS was searching by using the following terms “hydrotherapy,” “balneotherapy,” “spa therapy,” “spa treatment,” “creno-balneotherapy,” “water treatments,” and “aqua therapy,” on February 10th, 2022. The recorded data were the total number of articles, year of articles, country of articles, journal, document type, index data, and citation data. Also, the studies performed with natural source mineral water were marked to make a further subgroup analysis through quality and quantity. We obtained 816 articles; 667 (81.74%) were original research articles, and 149 (18.26%) were review articles. A statistically significant and increasing trend was shown in the publication about water treatments (p < 0.01). About three-quarters of the trials were sourced from high-income countries. Italy (n = 98; 12.01%); Turkey (n = 75; 9.19%); Australia (n = 65; 7.97%); Brazil (n = 46; 5.64%); and France (n = 38; 4.66%) were the most productive countries. Calculating the number of articles per million population, Hungary (3.38), Australia (2.53), and Italy (1.64) ranked in the top three. According to 100 billion dollars GDP, the top three countries were Brazil (24.41), Hungary (21.15), and Turkey (10.41). In the average citation calculation, the Netherlands (60.84), Israel (29.86), and Australia (29.06) were in the top three. The International Journal of Biometeorology was the leading journal for publication trials about water treatments. In the subgroup analysis, we found the total number of studies performed with natural source mineral water and non-specified source water trials as 430 and 386, respectively. We also presented that the natural source and non-specified water trials had a statistically significant and increasing trend between 2000 and 2021 (p < 0.01 and p < 0.01, respectively). The trials performed with natural source water mainly were sourced from Italy (n = 79; 18.37%), Turkey (n = 61; 14.19%), France (n = 38; 8.84%), Poland (n = 30; 6.98%), and Hungary (n = 29; 6.74%), the trials performed with non-specified water were sourced from Australia (n = 61; 15.80%), Brazil (n = 46; 11.92%), USA (n = 27; 6.99%), Italy (n = 19; 4.92%), and England (n = 18; 4.66%). The top journal of the natural source water trials was the International Journal of Biometeorology (n = 65; 15.12%), and for the non-specified water trials, it was the International Journal of Sports Physiology (n = 12; 3.11%).Our study presented an increasing trend in trial publications regarding water treatments between 2000 and 2021. Most of the trials were from high and upper-middle-income countries. We suggest that by demonstrating global productivity worldwide, our results can create more scientific attention on this topic and may promote the quantity and quality of the trials.

PMID:35779167 | DOI:10.1007/s00484-022-02323-0

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Hypoglossal nerve stimulation versus positive airway pressure therapy for obstructive sleep apnea

Sleep Breath. 2022 Jul 2. doi: 10.1007/s11325-022-02663-6. Online ahead of print.

ABSTRACT

PURPOSE: Hypoglossal nerve stimulation (HNS) has been shown to treat obstructive sleep apnea (OSA) effectively. The aim of this study was to compare HNS with positive airway pressure (PAP) treatment regarding outcome parameters: (1) sleepiness, (2) apnea-hypopnea index (AHI), and (3) effectiveness.

METHODS: Propensity score matching with nearest neighbor algorithm was used to compare outcomes of HNS and PAP therapy in a real-world setting. Data were collected at baseline and 12 months after initiating OSA treatment including demographics, Epworth Sleepiness Scale (ESS), AHI, and objective adherence data. To account for overall treatment efficacy, the mean disease alleviation (MDA) was calculated.

RESULTS: Of 227 patients who received treatment consecutively, 126 could be matched 1:1 with regard to age, body mass index, and AHI. After matching, no statistically significant differences between the groups were found. A clinically important symptom improvement was seen at 12 months in both cohorts, though there was a greater difference in ESS improvement in patients treated with HNS (8.0 ± 5.1 points vs. 3.9 ± 6.8 points; p = 0.042). In both groups, mean posttreatment AHI was significantly reduced (HNS: 8.1 ± 6.3/h; PAP: 6.6 ± 8.0/h; p < 0.001). Adherence after 12 months among patients treated with HNS was higher than in those receiving PAP therapy (5.0 ± 2.6 h/night; 4.0 ± 2.1 h/night) but not with statistical significance. Overall effectiveness calculated with the MDA was 59% in patients treated with HNS compared to 51% receiving PAP.

CONCLUSION: Patients treated with HNS therapy had significantly greater improvements in daytime sleepiness compared to PAP therapy, while the mean reduction of AHI and overall effectiveness were comparable for both treatments.

TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT03756805.

PMID:35779166 | DOI:10.1007/s11325-022-02663-6

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Patients with femoral neck fractures treated by bipolar hemiarthroplasty have superior to unipolar hip function and lower erosion rates and pain: a systematic review and meta-analysis of randomized controlled studies

Eur J Orthop Surg Traumatol. 2022 Jul 2. doi: 10.1007/s00590-022-03320-0. Online ahead of print.

ABSTRACT

PURPOSE: We assessed acetabular erosion, hip function, quality of life (QoL), pain, deep infection, mortality, re-operation and dislocation rates in patients with displaced femoral neck fractures (dFNFs) treated with unipolar versus bipolar hemiarthroplasty at different postoperative time points.

METHODS: Relevant Randomized Controlled Trials (RCTs) were identified, following comprehensive literature research in Medline, Cochrane Central and Scopus databases, from conception until August 31th, 2021 and analyzed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

RESULTS: Database research retrieved 120 studies; sixteen met eligibility criteria, providing 1813 (1814 hips) evaluable patients. Acetabular erosion was significantly higher for unipolar group at 6 and 12 months (p = 0.02 and p = 0.01 respectively). Patients in the bipolar group presented significantly better hip function at 12 and 24 months (p = 0.02 and p = 0.04 respectively). Postoperative pain was significantly less in the bipolar group at 12, 24 and 48 months (p = 0.01). No statistically significant differences were found regarding the postoperative rates of deep infection, mortality, re-operation and dislocation.

CONCLUSION: This study showed that patients with dFNFs treated with bipolar hemiarthroplasty have lower acetabular erosion rates at 6 and 12 months postoperatively, better hip function at 12 and 24 months, better QoL and less pain, when compared with unipolar. No statistically significant difference could be established regarding deep infection, mortality, re-operation and dislocation rates.

PMID:35779144 | DOI:10.1007/s00590-022-03320-0