Translation and Validation of the Health Literacy Score-14 Questionnaire for Vietnamese Patients with Diabetes.

Introduction: Health literacy (HL) is a crucial indicator for health promotion and diabetes care improvement, but the available measurements are mostly in English. This study aimed to translate and validate the 14-item Health Literacy Scale (HLS-14) questionnaire from English to Vietnamese for patients with diabetes in Vietnam. Methods: We translated HLS-14 into Vietnamese in accordance with the World Health Organization guidelines and conducted a cross-sectional survey among 571 outpatients with type 2 diabetes using the HLS-14 Vietnamese version (HLS-14 VN). The reliability and validity of the tool were assessed using Cronbach's alpha, composite reliability (CR), average variance extracted (AVE), and maximum shared variance (MSV), and confirmatory analysis was conducted. Results: Cronbach's alpha coefficients for the three subscales as in the original version were 0.931, 0.810, and 0.928 for functional HL, communicative HL, and critical HL, respectively. However, AVE for critical HL was 0.488, which improved to 0.516 after the removal of one item in the communicative HL. For all subscales in the revised 13-item version (HLS-13 VN), CR was above 0.8, AVE was above 0.5, and MSV was less than AVE. Confirmatory analysis of HLS-13 VN revealed an acceptable fit with comparative fit index of 0.983, goodness-of-fit index of 0.963, and root mean squared error of approximation of 0.058. Conclusions: The reliability and validity of HLS-13 VN were confirmed. The tool is suitable for use in clinical settings in Vietnam to assess multidimensional HL in patients with type 2 diabetes.

Multi-Omics after O-GlcNAc Alteration Identifies Cellular Processes Working Synergistically to Promote Aneuploidy.

Pharmacologic or genetic manipulation of O-GlcNAcylation, an intracellular, single sugar post-translational modification, are difficult to interpret due to the pleotropic nature of O-GlcNAc and the vast signaling pathways it regulates. To address this issue, we employed either OGT (O-GlcNAc transferase), OGA (O-GlcNAcase) liver knockouts, or pharmacological inhibition of OGA coupled with multi-Omics analysis and bioinformatics. We identified numerous genes, proteins, phospho-proteins, or metabolites that were either inversely or equivalently changed between conditions. Moreover, we identified pathways in OGT knockout samples associated with increased aneuploidy. To test and validate these pathways, we induced liver growth in OGT knockouts by partial hepatectomy. OGT knockout livers showed a robust aneuploidy phenotype with disruptions in mitosis, nutrient sensing, protein metabolism/amino acid metabolism, stress response, and HIPPO signaling demonstrating how OGT is essential in controlling aneuploidy pathways. Moreover, these data show how a multi-Omics platform can discern how OGT can synergistically fine-tune multiple cellular pathways.

Trichodysplasia Spinulosa.

Trichodysplasia spinulosa (TS) is a unique, rare clinical and histological dermatologic entity described mainly in a setting of immunosuppression. It is caused by a novel human polymoavirus, TS-associated polyomavirus. Reduction of immunosuppression and/or anti-viral therapy is the main therapeutic strategies used to treat such cases. We report a biopsy-proven case of TS in a male renal transplant patient who presented to a dermatology outpatient clinic in Montreal, Canada, in 2015. He was managed with valgancyclovir with no obvious response. Subsequently, a trial of topical imiquimod was commenced. Awareness of TS can prompt early diagnosis and management to prevent possible complications.

Vancomycin and Ustekinumab Combination Therapy in Acute Ulcerative Colitis.

The role of antibiotics in the treatment of ulcerative colitis is limited. We present a case of a 25-year-old woman who presented with a flare of ulcerative colitis after an episode of infectious gastroenteritis on a background of known primary sclerosing cholangitis. After the flare, she experienced persistent abdominal pain and diarrhea associated with elevated fecal calprotectin and deep rectosigmoid ulcerations on endoscopy. After unsuccessful trials of vedolizumab, infliximab, and tofacitinib, the patient was commenced on ustekinumab, tacrolimus, and oral vancomycin. Tacrolimus was ceased successfully, but while on maintenance ustekinumab therapy, 2 attempts to cease vancomycin resulted in symptom recurrence and rising fecal calprotectin that improved with vancomycin recommencement. To date, the patient has been on vancomycin continuously for 18 months and remains clinically well with colonoscopy demonstrating inactive colitis. This case highlights how vancomycin may be beneficial in the management of treatment-refractory ulcerative colitis as an adjunct to biologic therapy.

Mortality prognosis of NGAL, NTproBNP, hsTnT, and GRACE score in patients with acute coronary syndrome.

Background: NGAL serum concentration have predictive value for cardiovascular events and mortality in patients with acute coronary syndrome (ACS). Objectives: Assessed the all-cause mortarlity prognosis value of serum neutrophil gelatinase-associated lipocalin (NGAL), combination with N-terminal pro B-type natriuretic peptide (NT-proBNP), and hsTnT, and GRACE score in patients with ACS. Materials and methods: We conducted a cross-sectional analysis study used in this study in 58 patients with ACS. Serum NGAL, NT-proBNP, hs-TnT concentration and GRACE score associated with death events (after 3 months of follow-up) were assessed by receiver operating characteristic (ROC) curve. Results: High performance in predicting mortality of NGAL with a cut-off value of 154.55 ng/mL (AUC, 95% CI = 0.96, 0.90 - 1.0; p = 0.001), GRACE score with 140.50 scores (AUC, 95% CI = 0.76, 0.57 - 0.96; p = 0.051). Combination of NTproBNP plus NGAL indicated with the highest value (AUC, 95% CI = 0.96, 0.91 - 1.0; Se = 80.0; Sp = 92.5; p = 0.001). The relative risk assessment indicated a high value in mortality prediction of NGAL with a cut-off value of 154.55 (OR, 95% CI = 49.0, 4.3 - 549.2; p < 0.001), and GRACE score with 140.50 scores (OR, 95% CI = 11.1, 1.1 - 108.4; p = 0.013). Conclusion: NGAL can be employed as a biomarker for the early prediction of mortality events in individuals with ACS. The combination of NGAL, NT-proBNP, hsTnT, and GRACE score showed the higher outcome but not worth mentioning.

The ribosomal transcription units of five echinostomes and their taxonomic implications for the suborder Echinostomata (Trematoda: Platyhelminthes).

Five newly obtained nuclear ribosomal transcription unit (rTU) sequences from Echinostomatidae and Echinochasmidae are presented. The inter- and intrafamilial relationships of these and other families in the suborder Echinostomata are also analyzed. The sequences obtained are the complete rTU of Artyfechinostomum malayanum (9,499 bp), the near-complete rTU of Hypoderaeum conoideum (8,076 bp), and the coding regions (from 5'-terminus of 18S to 3'-terminus of 28S rRNA gene) in Echinostoma revolutum (6,856 bp), Echinostoma miyagawai (6,854 bp), and Echinochasmus japonicus (7,150 bp). Except for the longer first internal transcribed spacer (ITS1) in Echinochasmus japonicus, all genes and spacers were almost identical in length. Comprehensive maximum-likelihood phylogenies were constructed using the PhyML software package. The datasets were either the concatenated 28S + 18S rDNA sequences (5.7-5.8 kb) from 60 complete rTUs of 19 families or complete 28S sequences only (about 3.8-3.9 kb) from 70 strains or species of 22 families. The phylogenetic trees confirmed Echinostomatoidea as monophyletic. Furthermore, a detailed phylogeny constructed from alignments of 169 28S D1-D3 rDNA sequences (1.1-1.3 kb) from 98 species of 50 genera of 10 families, including 154 echinostomatoid sequences (85 species/42 genera), clearly indicated known generic relationships within Echinostomatidae and Echinochasmidae and relationships of families within Echinostomata and several other suborders. Within Echinostomatidae, Echinostoma, Artyfechinostomum, and Hypoderaeum appeared as monophyletic, while Echinochasmus (Echinochasmidae) was polyphyletic. The Echinochasmidae are a sister group to the Psilostomidae. The datasets provided here will be useful for taxonomic reappraisal as well as studies of evolutionary and population genetics in the superfamily Echinostomatoidea, the sole superfamily in the suborder Echinostomata.

Climate change: approach to intervention using expression vector for carbonic anhydrase via glycosylphosphatidylinositol.

Climate change is a change in the usual weather found in a place. The climate change has a major impact not only on natural disasters of the Earth but also on human health. The climate crisis is then no longer a future concern. It includes both the global warming driven by human emissions of greenhouse gases (GHG), and the resulting large-scale shifts in weather patterns. Global warming can occur from a variety of causes, both natural and human induced. The primary GHG in Earth's atmosphere, listed in decreasing order of average global mole fraction, are: water vapor (H2O), carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O), and ozone (O3). Today, scientists around the world continue to try and solve the puzzle of climate change. It is clear that to address climate change, the amount of CO2 released into the atmosphere by industrial process has to be reduced because once it is added to the atmosphere, it can continue to affect climate for thousands of years. For such a purpose, an approach to intervention using expression vectors for any protein targeting to the cell plasma membrane via the glycosylphosphatidylinositol, GPI, anchor is suggested. The resulting GPI-anchored proteins would be useful for studying intermolecular interactions, especially gene-environment interactions, in investigating the potential impact of any chemical compounds on any genes of interest and could be used for carbonic anhydrase (CA)-based CO2-capture (environmental application). This approach would be crucial not only for capturing CO2 via GPI and CA but also for the production of CA enzyme as well as its stabilization and therefore useful for combating the global warming of climate change.

The combination of CYP2C19 polymorphism and inflammatory cell ratios in prognosis cardiac adverse events after acute coronary syndrome.

Background: CYP2C19 gene polymorphism combination with inflammatory cell ratios was significant in the prognosis of coronary heart disease. Materials and methods: A cross-sectional analysis study, with 6 months follow-up on 142 patients with acute coronary syndrome. Patients were analyzed for CYP2C19 gene polymorphisms by real-time polymerase chain reaction (PCR) and complete blood count to determine inflammatory cell ratios and recorded cardiovascular events (CEs) after following up to 6 months. Results: For 90-day CEs, CYP2C19 gene polymorphism (Hazard Ratio (HR): 1.965, 95 % Confidence Interval (CI): 1.012-3.814), the combination of a neutrophil and lymphocyte ratio (NLR) ≥ 2.982 (HR: 13.001, 95 % CI: 1.37-97.304) or a platelet to lymphocyte ratio (PLR) ≥ 162.42 (HR: 2.878, 95 % CI: 1.212-6.835) was independent predictors of CEs. For 180-day CEs, CYP2C19 gene polymorphism combination with NLR ≥3.02 (HR: 13.946, 95 % CI: 1.833-106.121) or PLR ≥160.38 (HR: 5.349, 95 % CI: 1.379-20.745) or monocyte to lymphocyte ratio (MLR) ≥ 0.3 (HR: 4.699, 95 % CI: 1.032-31.393) were independent predictors of CEs. Conclusion: NLR, PLR or MLR combined with CYP2C19 gene polymorphism were stronger independent predictors of cardiovascular events in patients with acute coronary syndromes compared to CYP2C19 gene polymorphism and inflammatory cell ratios separately. CYP2C19 polymorphism and high NLR was the strongest predictor of both CEs at 90 days and 180 days.

Evaluating M2BPGi as a Marker for Liver Fibrosis in Patients with Chronic Hepatitis B.

BACKGROUND: The accurate evaluation of liver fibrosis is crucial for the treatment and follow up of chronic hepatitis B (CHB) patients. AIM: We examined the efficiency of serum Mac-2 Binding Protein Glycosylation isomer (M2BPGi) in diagnosing liver fibrosis stages in CHB patients. METHODS: A cross-sectional study was conducted on 177 adult CHB patients visiting the University Medical Center Ho Chi Minh City, Vietnam between October 2019 and December 2021. M2BPGi, ARFI, APRI, and FIB-4 were tested against FibroScan® for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The optimal M2BPGi cut-off values were identified based on the area under the receiver operating characteristic (AUROC) curve. RESULTS: There was a strong agreement between M2BPGi and FibroScan® (r = 0.77, P < 0.001). The optimal M2BPGi cut-off index (C.O.I) for detecting significant fibrosis (F ≥ 2) was 0.79 with an AUROC of 0.77, 67.3% sensitivity, 70% specificity, 60.6% NPV, and 75.3% PPV. Compared with APRI (61%) and FIB-4 (47%), M2BPGi had the greatest sensitivity for diagnosing F ≥ 2. M2BPGi combined with APRI yielded highest diagnosis performance for F ≥ 2 with an AUROC of 0.87. The optimal cut-off index of M2BPGi for diagnosing cirrhosis (F4) was 1.3 with an AUROC of 0.91, 88% sensitivity, 87.4% specificity, 97% NPV, and 61% PPV. The AUROC of M2BPGi for diagnosing F4 was comparable to that of ARFI (0.93). CONCLUSIONS: With cut-off values of 0.79 C.O.I and 1.3 C.O.I, M2BPGi could be an effective method for diagnosing significant fibrosis and cirrhosis in CHB patients, respectively.

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score.

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.

Loss of Twist1 and balanced retinoic acid signaling from the meninges causes cortical folding in mice.

Secondary lissencephaly evolved in mice due to effects on neurogenesis and the tangential distribution of neurons. Signaling pathways that help maintain lissencephaly are still poorly understood. We show that inactivating Twist1 in the primitive meninges causes cortical folding in mice. Cell proliferation in the meninges is reduced, causing loss of arachnoid fibroblasts that express Raldh2, an enzyme required for retinoic acid synthesis. Regionalized loss of Raldh2 in the dorsolateral meninges is first detected when folding begins. The ventricular zone expands and the forebrain lengthens at this time due to expansion of apical radial glia. As the cortex expands, regionalized differences in the levels of neurogenesis are coupled with changes to the tangential distribution of neurons. Consequentially, cortical growth at and adjacent to the midline accelerates with respect to more dorsolateral regions, resulting in cortical buckling and folding. Maternal retinoic acid supplementation suppresses cortical folding by normalizing forebrain length, neurogenesis and the tangential distribution of neurons. These results suggest that Twist1 and balanced retinoic acid signaling from the meninges are required to maintain normal levels of neurogenesis and lissencephaly in mice.

Phylogenotyping of infectious bursal disease virus in Vietnam according to the newly unified genotypic classification scheme.

Since 1987, infectious bursal disease virus (IBDV) has circulated and evolved in Vietnam, but little is known about the genotypes present. IBDV samples were collected in 1987, 2001-2006, 2008, 2011, 2015-2019, and 2021 in 18 provinces. We conducted phylogenotyping analysis based on an alignment of 143 VP2-HVR (hypervariable region) sequences from 64 Vietnamese isolates (26 previous and 38 additional sequences and two vaccines, and alignment of 82 VP1 B-marker sequences, including one vaccine and four Vietnamese field strains. The analysis identified three A-genotypes, A1, A3, and A7, and two B-genotypes, B1 and B3, among the Vietnamese IBDV isolates. The lowest average evolutionary distance (8.6%) was seen between the A1 and A3 genotypes, and the highest (21.7%) was between A5 and A7, while there was a distance of 14% between B1 and B3 and 17% between B3 and B2. Unique signature residues were observed for genotypes A2, A3, A5, A6, and A8, which could be used for genotypic discrimination. A timeline statistical summary revealed that the A3-genotype predominated (79.8% presence) in Vietnam from 1987 to 2021 and that it remained the dominant IBDV genotype over the last five years (2016-2021). The current study contributes to a better understanding of the circulating genotypes and evolution of IBDV in Vietnam and worldwide.

Risk Factors Associated With Polypharmacy and Potentially Inappropriate Medication Use in Ambulatory Care Among the Elderly in the United States: A Cross-Sectional Study.

INTRODUCTION: Polypharmacy, defined as the concurrent use of multiple (commonly five or more) prescription drugs, is widely prevalent among the elderly. It is a preventable and significant contributor to morbidity and mortality among older people. It is linked to prescribing potentially inappropriate medications (PIMs), which have been shown to be associated with an increased risk of adverse drug interactions and reduced compliance, and in some cases result in prescribing cascades where more drugs are prescribed to manage adverse outcomes. This study aimed to examine risk factors associated with polypharmacy and PIMs among elderly patients in outpatient settings in the US. METHODS: We conducted a cross-sectional analysis using the nationally representative National Ambulatory Medical Care Survey, between 2010 and 2016. We extracted data from all people aged 65 years or older and evaluated factors associated with polypharmacy and PIMs using multivariable logistic regression. Weights were applied to obtain national estimates. RESULTS: During the study period, there were a total of 81,295 ambulatory visits among adults 65 years and older. Being a woman (compared with a man) was more likely to be associated with greater prevalence of PIMs (OR: 1.31, 95% CI 1.23-1.40), and living in rural areas were more likely to be associated with both polypharmacy (OR: 1.15, 95% CI 1.07-1.23) and PIMs (OR: 1.19, 95% CI 1.09-1.29), compared with living in urban areas. Older age was positively associated with polypharmacy (OR: 1.08, 95% CI 1.06-1.10), but negatively associated with PIMs (OR: 0.97, 95% CI 0.95-0.99). CONCLUSIONS: Our study suggests age, being a woman, and living in rural areas are risk factors for both polypharmacy and PIMs usage. Aside from primary care providers' roles in managing polypharmacy, collaborative care with other specialty providers, such as clinical pharmacists, should also be considered as an approach to improving the quality of prescribing in geriatric patients. Future research should further explore reasons for polypharmacy and focus on deprescribing and quality improvement initiatives in primary care to lower polypharmacy among the elderly.

Focal Cryo-Immunotherapy with Intratumoral IL-12 Prevents Recurrence of Large Murine Tumors.

Focal ablation technologies are routinely used in the clinical management of inoperable solid tumors but they often result in incomplete ablations leading to high recurrence rates. Adjuvant therapies, capable of safely eliminating residual tumor cells, are therefore of great clinical interest. Interleukin-12 (IL-12) is a potent antitumor cytokine that can be localized intratumorally through coformulation with viscous biopolymers, including chitosan (CS) solutions. The objective of this research was to determine if localized immunotherapy with a CS/IL-12 formulation could prevent tumor recurrence after cryoablation (CA). Tumor recurrence and overall survival rates were assessed. Systemic immunity was evaluated in spontaneously metastatic and bilateral tumor models. Temporal bulk RNA sequencing was performed on tumor and draining lymph node (dLN) samples. In multiple murine tumor models, the addition of CS/IL-12 to CA reduced recurrence rates by 30-55%. Altogether, this cryo-immunotherapy induced complete durable regression of large tumors in 80-100% of treated animals. Additionally, CS/IL-12 prevented lung metastases when delivered as a neoadjuvant to CA. However, CA plus CS/IL-12 had minimal antitumor activity against established, untreated abscopal tumors. Adjuvant anti-PD-1 therapy delayed the growth of abscopal tumors. Transcriptome analyses revealed early immunological changes in the dLN, followed by a significant increase in gene expression associated with immune suppression and regulation. Cryo-immunotherapy with localized CS/IL-12 reduces recurrences and enhances the elimination of large primary tumors. This focal combination therapy also induces significant but limited systemic antitumor immunity.

Use of basal insulin in the management of adults with type 2 diabetes: An Asia-Pacific evidence-based clinical practice guideline.

The objective of this study was to provide recommendations regarding effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins (glargine U-300, degludec U-100, glargine U-100, detemir, and insulin protamine Hagedorn) in insulin-naïve adult patients with type 2 diabetes in the Asia-Pacific region. Based on evidence from a systematic review, we developed an Asia-Pacific clinical practice guideline through comprehensive internal review and external review processes. We set up and used clinical thresholds of trivial, small, moderate, and large effects for different critical and important outcomes in the overall certainty of evidence assessment and balancing the magnitude of intervention effects when making recommendations, following GRADE methods (Grading of Recommendations, Assessment, Development, and Evaluation). The AGREE (Appraisal of Guidelines, Research and Evaluation) and RIGHT (Reporting Items for practice Guidelines in HealThcare) guideline reporting checklists were complied with. After the second-round vote by the working group members, all the recommendations and qualifying statements reached over 75% agreement rates. Among 44 contacted external reviewers, we received 33 clinicians' and one patient's comments. The overall response rate was 77%. To solve the four research questions, we made two strong recommendations, six conditional recommendations, and two qualifying statements. Although the intended users of this guideline focused on clinicians in the Asia-Pacific region, the eligible evidence was based on recent English publications. We believe that the recommendations and the clinical thresholds set up in the guideline can be references for clinicians who take care of patients with type 2 diabetes worldwide.

Mitogenomic and nuclear ribosomal transcription unit datasets support the synonymy of Paragonimus iloktsuenensis and P. ohirai (Paragonimidae: Platyhelminthes).

The complete mitogenome (mtDNA) of nominal Paragonimus iloktsuenensis (Paragonimidae: Trematoda) and the nuclear ribosomal transcription unit (rTU) coding region (rTU*: from 5'-terminus of 18S to 3'-terminus of 28S rRNA gene, excluding the external spacer region) of this species and of P. ohirai were obtained and used to further support the previously suggested synonymy of these taxa in the P. ohirai complex. The complete mitogenome of P. iloktsuenensis was 14,827 bp long (GenBank: ON961029) and nearly identical to that of P. ohirai (14,818 bp; KX765277), with a 99.12% nucleotide identity. The rTU* was 7543 bp and 6932 bp in these two taxa, respectively. All genes and spacers in the rTU were identical in length, with exception of the first internal transcribed spacer, which contained multiple tandem repeat units (6.7 for P. iloktsuenensis and 5.7 for P. ohirai). There was near 100% identity for the rTU genes. The phylogenetic topology inferred from the mtDNA and from individual gene regions (partial cox1 of 387 bp and the ITS-2 of 282 bp - 285 bp) indicated a very close relationship consistent with synonymy of P. iloktsuenensis and P. ohirai. The datasets provided here will be useful for taxonomic reappraisal as well as studies of evolutionary and population genetics of the genus Paragonimus and family Paragonimidae.

Effectiveness, safety, initial optimal dose, and optimal maintenance dose range of basal insulin regimens for type 2 diabetes: A systematic review with meta-analysis.

AIMS: To investigate the effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins in insulin-naïve patients with type 2 diabetes mellitus. METHODS: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from January 2000 to February 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was adopted. The registration ID is CRD42022319078 in PROSPERO. RESULTS: Among 11 163 citations retrieved, 35 publications met the planned criteria. From meta-analyses and network meta-analyses, we found that when injecting basal insulin regimens at bedtime, the optimal choice in order of most to least effective might be glargine U-300 or degludec U-100, glargine U-100 or detemir, followed by neutral protamine hagedorn (NPH). Injecting glargine U-100 in the morning may be more effective (ie, more patients archiving glycated hemoglobin < 7.0%) and lead to fewer hypoglycemic events than injecting it at bedtime. The optimal starting dose for the initiation of any basal insulins can be 0.10-0.20 U/kg/day. There is no eligible evidence to investigate the optimal maintenance dose for basal insulins. CONCLUSIONS: The five basal insulins are effective for the target population. Glargine U-300, degludec U-100, glargine U-100, and detemir lead to fewer hypoglycemic events than NPH without compromising glycemic control.

The impact of access to financial services on mitigating COVID-19 mortality globally.

The COVID-19 pandemic has disproportionately affected different social and demographic groups, deepening the negative health implications of social and economic inequalities and highlighting the importance of social determinants of health. Despite a deep literature on pandemic-related disparities, specifically regarding social determinants and health outcomes, the influence of the accessibility of financial services on health outcomes during COVID-19 remains largely unexplored. Modeling (pre-omicron) COVID-19 mortality across 142 nations, we assess the impact of national-level usage and access to formal financial services. Two financial access indexes constructed through principal component analysis capture (1) usage of and access to formal financial tools and (2) reliance on alternative and informal financial tools. On average, nations with higher pre-pandemic use of and access to formal financial services had substantially lower population mortality risk from COVID-19, controlling for key population health, demographic, and socioeconomic covariates. The scale of effect is similar in magnitude-but opposite in direction-to major risk factors identified in previous literature, such as lung cancer, hypertension, and income inequality. Findings suggest that financial services deserve greater attention both in the public health literature related to COVID-19 and more broadly in policy discussions about fostering better public health overall.

Relationship Between Serum Ustekinumab Trough Concentration and Clinical and Biochemical Disease Activity: A Real-World Study in Adult Patients with Crohn's Disease.

BACKGROUND AND OBJECTIVES: The role of therapeutic drug monitoring for ustekinumab in the treatment of Crohn's disease has not been defined. This study aimed to explore the relationship of serum ustekinumab trough concentration (UTC) with clinical and biochemical disease outcomes in a real-world setting. METHODS: We performed a retrospective analysis of Crohn's disease patients treated at a single tertiary centre. Ustekinumab was given as a single intravenous induction dose, followed by maintenance subcutaneous injections every 4 to 8 weeks. Rates of clinical remission (Harvey-Bradshaw Index ≤ 4), biochemical remission (C-reactive protein < 5 mg/l and faecal calprotectin < 150 µg/g) and complete remission were assessed at baseline and at the time of UTC testing during maintenance therapy. The association between baseline variables and UTC was tested using linear regression. We also performed an external validation analysis of UTC cut-offs established in four previously published studies. RESULTS: This study included 43 patients. Compared to 8-weekly dosing, a 2.49- and 2.65-fold increase in UTC was associated with 6-weekly and 4-weekly dosing respectively. However, there was no significant difference in clinical, biochemical or complete remission among the dosing groups. An external validation of previously published optimal UTC cut-offs found low predictive value for our patient population. CONCLUSIONS: In this study, dosing interval was the only determinant significantly associated with a higher UTC for patients on maintenance ustekinumab therapy. While a higher UTC may be achieved with dose escalation, it was not associated with improved rates of clinical or biochemical response in our cohort.