Kidney outcomes with SGLT2is for type 2 diabetes patients: does background treatment with metformin or RASis matter?

Introduction: There is a lack of real-world evidence regarding the impact of concomitant metformin and renin-angiotensin system inhibitors (RASis) on sodium-glucose cotransporter-2 inhibitor (SGLT2i)-associated kidney outcomes. This study was aimed to investigate whether SGLT2i-associated kidney outcomes were modified by the concomitant use of metformin or RASis in patients with type 2 diabetes. Methods: SGLT2i users were identified from three electronic health record databases during May 2016 and December 2017 and categorized into those with and without concomitant use of metformin or RASis. Propensity score matching was performed to minimize baseline differences between groups. Study outcomes were mean estimated glomerular filtration rate (eGFR) change and time to 30%, 40%, and 50% eGFR reductions. A meta-analysis was performed to combine the estimates across databases. Results: After matching, there were 6,625 and 3,260 SGLT2i users with and without metformin, and 6,654 and 2,746 SGLT2i users with and without RASis, respectively. The eGFR dip was similar in SGLT2i users with and without metformin therapy, but was greater in SGLT2i users with RASis compared to those without RASis. Neither metformin nor RASi use had a significant effect on SGLT2i-associated eGFR reductions, as evidenced by the hazard ratios (95% CIs) of 30% eGFR reductions for SGLT2is with versus without metformin/RASis, namely 1.02 (0.87-1.20)/1.09 (0.92-1.31). Such findings were also observed in the outcomes of 40% and 50% eGFR reductions. Conclusion: Using metformin or RASis did not modify SGLT2i-associated kidney outcomes in type 2 diabetes.

Longitudinal economic burden of incident complications among metabolic syndrome populations.

BACKGROUND: This study quantifies the longitudinal economic burden for a wide spectrum of incident complications, metabolic syndrome (MS)-related risk factors, and comorbidities in patients with MS. METHODS: This retrospective study utilized linked data from the 2013 National Health Interview Survey and the 2012-2021 National Health Insurance Research Database to identify MS individuals and their characteristics. The incidence rate of each complication was calculated as the number of complication events in the study period divided by the total person-years during follow-up. The healthcare costs of complications were analyzed using a generalized estimating equation model to determine the cost impact of complications after adjustment for patients' characteristics. Sensitivity analyses on variables with high missing rates (i.e., cause of death, body mass index) were performed. RESULTS: Among 837 identified MS individuals over 8.28 (± 1.35) years of follow-up, the most frequent complications were microvascular diseases (incidence rate for nephropathy/retinopathy/neuropathy: 6.49/2.64/2.08 events per 100 person-years), followed by cardiovascular diseases (2.47), peripheral vascular diseases (2.01), and cancers (1.53). Death was the costliest event (event-year cost per person: USD 16,429) and cancers were the most expensive complications (USD 9,127-11,083 for non-MS- and MS-related cancers). Developing non-MS/MS-related cancers, cardiovascular diseases, and obesity-related medical conditions increased annual costs by 273% (95% CI: 181-397%)/175% (105-269%), 159% (118-207%), and 140% (84-214%), respectively. Microvascular diseases had the lowest cost impact on annual costs (i.e., 27% [17-39%]/27% [11-46%]/24% [11-37%] increases for nephropathy/neuropathy/retinopathy, respectively). Having existing comorbidities increased annual costs by 20% (osteoarthritis) to 108% (depression). Having morbid obesity (i.e., body mass index ≥ 35 kg/m2) increased annual costs by 58% (30-91%). CONCLUSIONS: The economic burden from costly incident complications (i.e., cardiovascular diseases, peripheral vascular diseases, cancers), MS-related risk factors (i.e., morbid obesity), and comorbidities (i.e., depression) highlight the urgent need for early intervention to prevent MS and its progression. The comprehensive cost estimates reported in this study can facilitate the parameterization of economic analyses to identify cost-effective interventions for these patients.

Clinical efficacy of ertapenem vs. other carbapenems for the treatment of extended-spectrum-ß-lactamase-producing Enterobacterales infection: A systematic review and meta-analysis.

OBJECTIVE: Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-ß-lactamase (ESBL)-producing Enterobacterales infection. However, whether ertapenem is as effective as other carbapenems for ESBL-producing Enterobacterales remains unclear. Therefore, this meta-analysis was conducted to compare the clinical efficacy of ertapenem versus other carbapenems in the treatment of ESBL-producing Enterobacterales infection. METHODS: PubMed, Web of Science, and Cochrane Library were searched from their inception to 29 November 2022. Only studies comparing ertapenem and other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections were included. RESULTS: A total of six studies meeting selection criteria were identified. Overall, ertapenem was associated with a significantly lower 30-d mortality when compared with other carbapenems (10.7% [46/431] vs. 17.7% [104/586]; risk ratio [RR], 0.61; 95% CI: 0.40-0.91). The ertapenem group exhibited a significantly shorter length of hospital stay than the other carbapenem groups (mean differences, -6.02 d; 95% CI, -9.39 to -2.64). No significant differences were noted between ertapenem and other carbapenem groups in terms of rates of clinical cure or improvement (RR, 1.11; 95% CI: 0.97-1.25) and microbiological eradication (RR, 1.01; 95% CI: 0.97-1.06). CONCLUSIONS: Ertapenem could be as effective as other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections.

Distribution of ß-lactamases and emergence of carbapenemases co-occurring Enterobacterales isolates with high-level antibiotic resistance identified from patients with intra-abdominal infection in the Asia-Pacific region, 2015-2018.

PURPOSE: In this study, we aimed to assess the geographic distribution and molecular characteristics of ß-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia-Pacific region. METHOD: Isolates were investigated for extended-spectrum ß-lactamases (ESBLs), AmpC ß-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing. RESULT: A total of 832 Enterobacterales isolates from 8 different countries with ß-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC ß-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC ß-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %. CONCLUSION: The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia-Pacific region.

Weight Gain Associated with COVID-19 Lockdown in Children and Adolescents: A Systematic Review and Meta-Analysis.

BACKGROUND: Lockdown is an effective nonpharmaceutical intervention to reduce coronavirus disease 2019 (COVID-19) transmission, but it restricts daily activity. We aimed to investigate the impact of lockdown on pediatric body weight and body mass index (BMI). METHODS: The systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Four online databases (EMBASE, Medline, the Cochrane Library and CINAHL) were searched. RESULTS: The pooled results showed that lockdown was associated with significant body weight gain (MD 2.67, 95% CI 2.12-3.23; p < 0.00001). The BMI of children with comorbidities or obesity did not change significantly. The BMI of general population was significantly higher during lockdown than before the pandemic (MD 0.94, 95% CI 0.32-1.56; p = 0.003). However, heterogeneity was high (I2 = 84%). Among changes in weight classification, increases in the rates of obesity (OR 1.23, 95% CI 1.10-1.37; p = 0.0002) and overweight (OR 1.17, 95% CI 1.06-1.29; p = 0.001) were reported. CONCLUSIONS: Our meta-analysis showed significant increases in body weight and BMI during lockdown among school-age children and adolescents. The prevalence of obesity and overweight also increased. The COVID-19 pandemic worsened the burden of childhood obesity.

Streptococcus gallolyticus - A potentially neglected pathogen causing neonatal sepsis not covered by routine group B streptococcus screening.

We report 4 cases of neonatal sepsis caused by Streptococcus gallolyticus. The clinical course was quite similar to early-and late-onset group B streptococcus disease. None of the mothers had group B streptococcus (GBS) colonization on prenatal screening nor received intrapartum antibiotics. We proposed the sporadic distribution of S. gallolyticus sepsis among neonates was partly due to relatively low colonization rate in adults compared with GBS. Species determination of S. gallolyticus may not be available using conventional microbiological methods and may contribute to underestimation or misclassification. In our series, we highlighted the importance of S. gallolyticus as an important pathogen in neonatal sepsis deserving further surveillance.

Severe Mycoplasma pneumoniae infections with prolonged fever in a child: Delayed treatment is as important as macrolide resistance.

We report a 7-year-old girl who got Mycoplasma pneumoniae infection with prolonged fever. Macrolide was used on day 14 of illness but fever persisted with progressive lung consolidation. Oral prednisolone was administered on day 33 then fever subsided with dramatically clinical improvement (decreased CRP and resolution of lung consolidation). In this case, delayed effective antibiotic treatment with inflammation may be the major factor contributing to the fever rather than ongoing infection.

Health care utilization pattern prior to maltreatment among children under five years of age in Taiwan.

BACKGROUND: Several studies have hypothesized that the pattern of health care utilization among maltreated children differ from others without the experience. However, the conclusions have not been consistent. OBJECTIVE: The study aims to examine whether the pattern of health care utilization among children 0-5 years old with maltreatment different from their counterparts without maltreatment in Taiwan. SUBJECTS AND SETTING: All children born in 2007 in Taiwan. METHOD: This is a population-based and case-controlled study. Cases are children under five years of ago with maltreatment-related diagnosis in the claims data of the National Health Insurance in Taiwan during the 2007-2013 period. For each case, there were 10 birth date-matched controls. Exposure variables include the number of injury or non-injury-related outpatients, emergency department (ED) visits, and hospitalization. Multivariate models were employed, with adjustment for sex, urbanization level, and comorbidities of children. RESULTS: Of children born in 2007, 382 had maltreatment-related diagnosis during the age of 0-5. The adjusted odds ratio (aOR) for having two or more ED visits with or without injury-related diagnosis is 3.52 (95% CI 1.75-7.07) and 2.0-0 (95% CI 1.47-2.72), respectively. Children with maltreatment also had significantly higher number of hospitalization without injury-related diagnosis and aOR for those having two more hospitalizations stands at 2.47 (95% CI 1.59-3.83). CONCLUSIONS: Children with maltreatment when 0-5 years old had higher number of ED visits with injury-related diagnosis, as well as hospitalization without injury-related diagnosis. Recognition of the health care utilization is conducive to early identification of children with risk for maltreatment.

Thiamine for preventing dementia development among patients with alcohol use disorder: A nationwide population-based cohort study.

OBJECTIVE OF STUDY: Alcohol use disorder is one of the most important factors contributing to dementia. This study examined the protective effect of thiamine administration on the incidence of dementia among patients with alcohol use disorder in Taiwan by evaluating a nationwide database. METHODS: We retrieved data for this retrospective cohort study from the Longitudinal Health Insurance Database 1995-2000. Patients receiving thiamine therapy after the diagnosis of alcohol use disorder were recruited as the thiamine therapy (TT) group, and the comparison group without TT (NTT group) included randomly assigned and age-, sex-, and index year-matched individuals with alcohol use disorder. Demographic data, comorbid medical disorders, and psychotropic medication use were evaluated and controlled. The cumulative defined daily dose (DDD) was analyzed to demonstrate the dose effect. RESULTS: Each group had 5059 patients. The TT group had a lower crude hazard ratio (0.76; 95% confidence interval: 0.60-0.96) of dementia than the NTT group. After adjusting for demographic data, comorbidity, and psychotropic medication use, the adjusted hazard ratio was 0.54 (95% confidence interval: 0.43-0.69). The significance existed among TT subjects with cumulative DDD higher than 23. The Kaplan-Meier analysis demonstrated a lower cumulative incidence of dementia in the TT group than in the NTT group. CONCLUSION: The results indicated that thiamine therapy could be a protective factor for dementia development in patients with alcohol use disorder. Thiamine therapy should be a crucial part of the treatment plan and health policies to prevent dementia development or progression among patients with alcohol use disorder.

Energy replacement using glucose does not increase postprandial lipemia after moderate intensity exercise.

BACKGROUND: Aerobic exercise can decrease postprandial triglyceride (TG) concentrations but the relationship between exercise-induced energy deficits and postprandial lipemia is still unclear. The aim of the present study was to examine the effect of a single bout of aerobic exercise, with and without energy replacement, on postprandial lipemia and on peripheral blood mononuclear cell (PBMC) mRNA expression of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) receptors and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). METHODS: Nine healthy male humans completed three two-day trials in a random order. On day 1, volunteers rested (CON), completed 60 minutes of treadmill walking at 50% of VO2peak (EX) or completed the same bout of walking but with the energy replaced afterwards with a glucose solution (EXG). On day 2, volunteers rested and consumed a high fat test meal in the morning. RESULTS: Total and incremental TG AUC were significantly lower on the EXG (P < 0.05) and EX (P < 0.05) trials than the CON trial with no difference between the two exercise trials. No significant difference was observed in VLDL or LDL receptor mRNA expression among the trials (P > 0.05). CONCLUSIONS: In conclusion, energy replacement by glucose did not affect the decrease in postprandial TG concentrations observed after moderate intensity exercise and exercise does not affect changes in PBMC HMGCR, VLDL and LDL receptor mRNA expression.

Associated factors with syphilis among human immunodeficiency virus-infected men who have sex with men in Taiwan in the era of combination antiretroviral therapy.

BACKGROUND/PURPOSE: Little is known about the factors associated with syphilis among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) with access to combination antiretroviral therapy (cART) in Taiwan, where MSM has re-emerged as the leading risk group for HIV transmission. METHODS: From March to October 2011, MSM who regularly attended HIV clinics at a university hospital were invited to participate in the study. A structured questionnaire interview was conducted to collect information on sociodemographic characteristics, immunologic and virologic status, sexual partners and patterns of sexual behavior, and use of recreational drugs. RESULTS: During the study period, 310 HIV-infected MSM with a mean age of 35.5 years were enrolled, of which 82.3% (n = 255) were sexually active and 37.4% (n = 116) used recreational drugs in the past 6 months. Syphilis was self-reported in 46.5% (n = 144) of the participants after HIV infection was diagnosed and 37.5% (112/299) had serologic evidence of syphilis within 1 year before enrollment. Multivariate logistic regression analysis limited to those who were receiving cART showed that higher CD4 counts [adjusted odds ratio (AOR): 1.17; 95% confidence interval (CI): 1.02-1.34], lower educational achievement (AOR: 1.95; 95% CI: 1.05-3.63), serosorting (AOR: 3.32; 95% CI: 1.04-10.63), and use of recreational drugs (AOR: 2.55; 95% CI: 1.26-5.13) were associated with syphilis. CONCLUSION: Improved immune status, lower educational achievement, serosorting, and use of recreational drugs were associated with syphilis among HIV-infected MSM who were receiving cART. These findings suggest that strengthening client-specific counseling is needed to reduce risks for syphilis among HIV-infected MSM in Taiwan.

The bidirectional interactions between addiction, behaviour approach and behaviour inhibition systems among adolescents in a prospective study.

Internet addiction is a worldwide mental health problem among adolescents. This study aimed to evaluate the prediction of the Behaviour Inhibition System (BIS) and the Behaviour Approach System (BAS) on the occurrence of Internet addiction, and determine whether Internet addiction would make any difference on the development of BIS/BAS among adolescents. Adolescents in grade 7 were recruited to complete assessment for Internet addiction and BIS/BAS. Then, a follow-up was performed 1 year later. The results demonstrated that higher BAS and BAS fun seeking predicted the occurrence of Internet addiction. Adolescents with Internet addiction decreased more on BAS and BIS 1 year later than the non-addiction group. These results suggest that higher BAS and fun seeking are risk factors for Internet addiction among adolescents. Besides, interventions for Internet addiction should pay attention to the disturbed development of BAS and BIS.

Social anxiety in online and real-life interaction and their associated factors.

Social anxiety was compared between online and real-life interaction in a sample of 2,348 college students. Severity of social anxiety in both real-life and online interaction was tested for associations with depression, Internet addiction, Internet activity type (gaming versus chatting), and scores on Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales. The results showed that social anxiety was lower when interacting online than when interacting offline. Depression, Internet addiction, and high BIS and BAS scores were associated with high social anxiety. The social anxiety decreased more in online interaction among subjects with high social anxiety, depression, BIS, and BAS. This result suggests that the Internet has good potential as an alternative medium for delivering interventions for social anxiety. Further, the effect of BIS on social anxiety is decreased in online interaction. More attention should be paid for BIS when the treatment for social anxiety is delivered online.

Lactoferrin: an iron-binding antimicrobial protein against Escherichia coli infection.

Escherichia coli (E. coli) are the most common aerobic gram-negative bacilli in a normal intestinal tract. They cause most of the intra-abdominal infections, wound infections associated with abdominal surgery, and septicemia. Most of these infections are of endogenous intestinal origin. Lactoferrin (LF) is an iron-binding glycoprotein found in milk and various external secretions. This protein has been found to have a number of biological functions, including antimicrobial, anti-cancer, antioxidant, and immunomodulatory effects. Partial degradation of LF by pepsin can give rise to peptides termed lactoferricin (LFcin) with more potent antimicrobial activity. LF and LFcin have been shown to inhibit the growth of a number of pathogenic bacteria (including E. coli and antibiotic-resistant strains), fungi, and even viruses in both in vitro and in vivo studies. We previously demonstrated that both recombinant porcine LF (pLF) produced from yeast and a synthetic 20-residue porcine LFcin peptide exhibit antimicrobial activity in vitro. In one of our recent studies, we performed pathogen challenges, including pathogenic E. coli, Staphylococcus aureus and Candida albicans, of the digestive tract of a transgenic milk-fed animal model. The results showed that LF has broad spectrum antimicrobial activity in the digestive tract and protects the mucosa of the small intestine from injury. Our following study also revealed that pLF as a feedstuff additive enhances avian immunity, including antibody formation and cell-mediated immunity. All of these results suggest that LF could be a novel natural protein in the treatment and prevention of infections with E. coli or antibiotic-resistant bacteria strains.

A novel method for evaluation of improved survival trend for common cancer: early detection or improvement of medical care.

RATIONALE, AIMS AND OBJECTIVES: The improvement of survival with time for cancers has been observed worldwide. However, whether and to what extent such an improvement is attributed to early detection or the advance in medical technology is barely addressed. METHOD: We developed a novel graphic method to calculate attributable proportions related to two factors. This graphic method was first to calculate adjusted survival curve by the application of direct standardized epidemiological method to tumour staging. The crude survival curve was then compared with the adjusted survival curve. RESULTS: Cumulative survival curves of two time epochs, 1989-1993 (period 1) and 1994-1998 (period 2), on six common cancers collected from cancer registry of National Taiwan University between 1989 and 1998, were compared. The attributable proportions due to early detection and medical care were 77% and 23% for breast cancer, 50% and 50% for cervical cancer, 52% and 48% for colorectal cancer, 76% and 24% for gastric cancer, 66% and 34% for liver cancer, and 30% and 70% for prostate cancer respectively. CONCLUSION: Distinguishing between early detection from advance in medical care associated with the improvement of survival trend using our graphic method has a significant implication for secondary and tertiary prevention of common cancers.