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Researchers have identified that some subgroups of patients with diabetes, older males, smokers, and White ethnicity, are at significantly increased risk of developing diabetic foot ulcer disease (DFUD), a severe condition with a poorer five-year survival rate than most cancers. The study was published in Diabetes, Obesity & Metabolism by Safoora G. and colleagues. The research found that those with higher systolic blood pressure and a higher baseline HbA1c level were more likely to develop DFUD.
DFUD is a long-standing, life-changing diabetic complication that is frequently under-diagnosed with regard to its catastrophizing effects. Previously, almost all risk factor information was derived from small, clinic-based surveys that tended to be cross-sectional in design. The current study sought to address the deficit through the utilization of two large and independent English and Scottish diabetic cohorts, providing one of the largest analyses to date.
The research evaluated a combined total of 391,790 individuals with diabetes—131,042 from England via the Clinical Practice Research Datalink (CPRD), and 260,748 from Scotland via the Scottish Diabetes Research Network-National Diabetes Dataset (SDRN-NDS). The English cohort included primary and secondary care data, whereas the Scottish cohort utilized secondary care and foot clinic data.
Key Findings
Incidence of DFUD:
• In the English cohort, 4.7% of patients developed DFUD during a median follow-up of 4.3 years, representing an incidence rate of 9.0 per 1,000 person-years (95% CI: 8.8–9.2).
• In the Scottish cohort, 2.9% of patients developed DFUD during a median follow-up of 6.3 years, with an incidence rate of 4.4 per 1,000 person-years (95% CI: 4.3–4.5).
Common Risk Factors Identified in Both Populations:
• Age: The older patients had higher chances of developing DFUD.
• Sex: Males were more vulnerable.
• Ethnicity: Individuals of White ethnicity were having greater incidence rates.
• Lifestyle: Smokers were much more likely to develop DFUD.
• Clinical indicators: Greater systolic blood pressure and baseline HbA1c levels were strongly related with subsequent DFUD.
This study provides strong evidence to support the targeting of these high-risk groups in diabetes care programs. These findings can provide the impetus for more effective prevention strategies, lowering the life-changing costs of diabetic foot ulcer disease.
Reference:
Gharibzadeh S, Lee J, Highton P, Greenlaw N, Gillies C, Zaccardi F, Brennan A, Pollard DJ, Valabhji J, Game F, Stanley B, Leese G, Gray L, Tesfaye S, Webb D, Wild S, Shabnam S, Davies M, Khunti K, Petrie J, Gregg E. Risk factors for development of diabetic foot ulcer disease in two large contemporary UK cohorts. Diabetes Obes Metab. 2025 Jun 24. doi: 10.1111/dom.16519. Epub ahead of print. PMID: 40555701.
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China: A systematic review and meta-analysis published in BMJ Open has highlighted the alarming mortality rate among hospitalised adult patients with tetanus and identified key factors that significantly influence survival outcomes.
The study, conducted by Zhenlin Chen and colleagues from the Department of Emergency, Zhangzhou Affiliated Hospital of Fujian Medical University, analysed data from 22 observational studies comprising 1,618 adult patients admitted with tetanus between January 2000 and February 2024.
The study revealed the following findings:
According to the authors, the meta-analysis is the first of its kind to systematically evaluate mortality and associated risk factors in hospitalised adults with tetanus. Data were extracted independently by two reviewers from four major databases—PubMed, Web of Science, The Cochrane Library, and Embase. Statistical heterogeneity was assessed using the I² statistic, with subgroup and meta-regression analyses performed to explore potential sources of variation among the studies.
While the study provides valuable insights, the authors acknowledged certain limitations. Only four databases were searched, which may have resulted in the exclusion of relevant studies. Additionally, both univariate and multivariate analyses were considered for risk factor extraction, and the small sample size for certain variables may have affected the robustness of the results. Differences in statistical methodologies across studies were also noted as a factor warranting cautious interpretation.
Despite these constraints, the findings carry significant clinical and public health implications. The high mortality rate reinforces the urgent need to strengthen tetanus control measures, particularly focusing on adult immunisation and early intervention for high-risk patients. The identification of specific risk factors provides a framework for targeted care, potentially reducing fatalities in hospitalised cases.
The researchers stress that further large-scale, multicentre prospective studies are necessary to validate these findings and provide more detailed clinical insights. Until then, prioritising vaccination coverage, improving awareness of wound care, and promptly identifying patients at elevated risk could serve as key strategies in reducing tetanus-related deaths among adults.
Reference:
Chen Z, Lin Z, Zhang W, et alMortality and risk factors in hospitalised adult patients with tetanus: a systematic review and meta-analysis. BMJ Open 2025;15:e101782. doi: 10.1136/bmjopen-2025-101782
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USA: A substantial portion of patients diagnosed with heart failure with reduced ejection fraction (HFrEF) go on to experience meaningful improvement in cardiac function, but they remain at notable clinical risk—emphasizing the continued need for guideline-directed medical therapy (GDMT). The findings stem from a large, retrospective cohort study published in JACC by Dr. Kyung H. Min and colleagues from Kaiser Permanente San Francisco Medical Center.
Analyzing electronic health data from 28,292 patients with newly diagnosed HFrEF between 2013 and 2022, the study revealed the following:
Accompanying the study, an editorial by Drs. Andrew S. Perry and Lynne W. Stevenson from Vanderbilt University Medical Center emphasized the evolving landscape of heart failure treatment. They noted that while many patients benefit from GDMT, the heterogeneity of heart failure means that standard therapies may not be adequate for all. “The improvement journey will hopefully include new lanes as GDMT continues to evolve beyond traditional triple therapy,” they wrote.
Perry and Stevenson also highlighted the limitations of focusing solely on ejection fraction as a measure of heart failure progression. “The imminent era of broad population data will hopefully guide integration of primary and secondary causes, therapeutic responses, and multidimensional surveillance beyond EF, to personalize regimens and improve prognosis along all journeys with HF,” they suggested.
Ultimately, the study highlights both the encouraging potential for heart function recovery and the persistent vulnerability of patients even after improvement. Continued adherence to and optimization of GDMT remains crucial in managing HFimpEF, as personalized approaches based on emerging data may shape the future of care.
Reference:
Min KH, Go AS, Lee K, et al. Guideline-directed medical therapy and outcomes among patients with heart failure with improved ejection fraction. JACC. 2025;86:338-350.
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Anxiety during anesthesia induction in children is a significant concern, associated with various adverse outcomes, including behavioral issues and prolonged induction times. Approximately 50-67% of pediatric patients experience this anxiety, highlighting the necessity for effective management strategies. Nonpharmacological interventions, such as parental presence, psychological therapy, and virtual reality, have been proposed as alternatives to pharmacological methods like midazolam, which can have undesirable effects. However, the specific impacts of various nonpharmacological interventions remain ambiguous due to a scarcity of direct comparative studies.
Recent systematic review analyzed 34 randomized controlled trials (RCTs) involving 3,040 participants to compare the efficacy of different nonpharmacological interventions. A Bayesian network meta-analysis approach facilitated both direct and indirect comparisons, crucial given the lack of head-to-head trials. The primary outcomes measured included anxiety levels during induction, assessed using standardized scales such as the modified Yale Preoperative Anxiety Scale (mYPAS).
Results of Nonpharmacological Interventions
Results indicated that interventions combining parental presence with interactive distraction techniques (PDI-PPIA and IDI-PPIA) showed the highest efficacy in reducing anxiety during anesthesia induction, achieving statistical significance with standardized mean differences (SMD) of -1.94 and -1.83, respectively. In contrast, traditional parental presence interventions alone (PPIA) and other passive or interactive distractions were less effective, with SMDs ranging from -0.91 to -1.18. Notably, no interventions demonstrated a significant reduction in parental anxiety levels.
Quality Assessment of Studies
The meticulous quality assessment revealed a predominantly low to moderate risk of bias across studies, although some concerns were raised regarding outcome measurement, primarily due to observer blinding issues. Sensitivity analyses confirmed the primary findings, reinforcing the conclusion that specific nonpharmacological strategies provide effective means to mitigate preoperative anxiety in children. The analysis underscores the pressing need for future head-to-head trials to further delineate the comparative effectiveness of these strategies, particularly in diverse populations and settings. Subgroup analyses were constrained by limited data on intravenous versus inhalation induction methods, suggesting a vital area for future exploration. The findings advocate for the integration of tailored, family-centered interventions into clinical practice to enhance the overall perioperative experience for pediatric patients.
Key Points
– Anxiety prevalence during anesthesia induction in pediatric patients is significant, with 50-67% experiencing anxiety, leading to behavioral issues and prolonged induction times, necessitating effective management strategies.
– A systematic review of 34 randomized controlled trials (RCTs) involving 3,040 participants was conducted to evaluate the efficacy of various nonpharmacological interventions compared to traditional pharmacological methods.
– Bayesian network meta-analysis was utilized to facilitate both direct and indirect comparisons of interventions, with the primary outcome being anxiety levels during induction measured by standardized scales like the modified Yale Preoperative Anxiety Scale (mYPAS).
– Interventions combining parental presence with interactive distraction techniques (PDI-PPIA and IDI-PPIA) demonstrated the highest efficacy in reducing anxiety with significant standardized mean differences (SMDs) of -1.94 and -1.83, whereas traditional parental presence alone (PPIA) and other distraction methods showed lower efficacy (SMDs range from -0.91 to -1.18).
– Quality assessment of the included studies revealed a low to moderate risk of bias, with concerns primarily related to outcome measurement and observer blinding, though sensitivity analyses confirmed the robustness of the primary findings.
– The findings emphasize the necessity for future head-to-head trials to better understand the comparative effectiveness of nonpharmacological interventions, particularly in diverse populations, while advocating for family-centered strategies to improve the perioperative experience for pediatric patients.
Reference –
Yuanyuan Li et al. (2025). Nonpharmacological Interventions For Decreasing Anxiety During Anesthesia Induction In Children: A Systematic Review And Bayesian Network Meta-Analysis. *BMC Anesthesiology*, 25. https://doi.org/10.1186/s12871-025-03077-z.
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Researchers have determined in a new study published in EClinicalMedicine that patients with chronic kidney disease (CKD), even at its earliest stages, have a substantially elevated risk of requiring hospitalization for serious infection. The results concluded that reduced kidney function and increased excretion of albumin in the urine are independently and stepwise related to increased risk of infection, even in individuals with only mildly decreased kidney function. The study was conducted by Junichi I. and colleagues.
In this large, meta-analysis, one of the Chronic Kidney Disease Prognosis Consortium (CKD-PC), data from 47 international cohorts with 1,246,912 participants were combined. The investigators compared estimated glomerular filtration rate using serum creatinine (eGFRcr) and urinary albumin-to-creatinine ratio (ACR) to determine the association of these biomarkers with infection-related hospitalization. Infections were infections of the respiratory, urinary, skin, gastrointestinal, genital, nervous, and cardiovascular tracts, and sepsis. Follow-up information was collected through December 31, 2019.
This analysis employed individual participant data from 1.2 million people in 47 cohorts worldwide, for which their eGFRcr and ACR were measured. Both the markers were analyzed as continuous and categorical markers. Acute infection hospitalization was monitored through discharge diagnostic codes, with follow-up censored in December 2019 or at cohort closure. Cox models of proportional hazards were employed to calculate the hazard ratios (HRs) for risk of infection associated with kidney function and with levels of albuminuria.
Key Findings
• Of more than 1.2 million participants, 170,864 persons (13.7%) were hospitalized for infections in follow-up.
• The overall rate of incidence (IR) was 22.0 per 1000 person-years (interquartile interval: 16.2–31.0).
• Relative to those with eGFRcr 90–104 ml/min/1.73 m² and ACR <10 mg/g:
• Patients with eGFRcr 60–89 had an HR of 1.09 (95% CI: 1.06–1.13)
• Individuals with eGFRcr 45–59 had an HR of 1.39 (95% CI: 1.34–1.45)
• ACR 10–29 mg/g was correlated with an HR of 1.40 (95% CI: 1.33–1.47)
• ACR 30–299 mg/g had an HR of 1.82 (95% CI: 1.72–1.92)
• Individuals with extremely high eGFRcr ≥105 ml/min/1.73 m² also had higher infection risk (HR: 1.22; 95% CI: 1.17–1.26)—a surprising result indicating non-linear relations at extreme levels.
• The highest risk was seen in those with both extremely low eGFRcr (<30 ml/min/1.73 m²) and elevated ACR (≥300 mg/g), with combined HR of 6.27 (95% CI: 5.70–6.90)—more than six times as high as the reference group.
• These trends were consistent regardless of the type of infection. For instance, HR of lower respiratory tract infections was 1.26 (95% CI: 1.22–1.30) per 15 ml/min/1.73 m² reduction in eGFRcr, and 1.48 (95% CI: 1.44–1.53) per 8-fold rise in ACR.
Risk of infection in CKD patients is significant, and this risk starts early in the progression of kidney impairment. The authors of the study concluded that both worsening kidney function and rising albuminuria are independent, additive predictors of hospitalization with infection. These results necessitate specific infection prevention measures not only in those with severe CKD but also in people in preceding stages of kidney disease.
Reference:
Ishigami, J., Surapaneni, A., Matsushita, K., Coresh, J., Grams, M. E., Ballew, S. H., Sang, Y., Stengel, B., Ärnlöv, J., Bell, S., Carrero, J.-J., Chang, A. R., Ciemins, E. L., Haynes, R., Ix, J., Kotsis, F., Lees, J. S., Pandit, K., Rao, P., … Surapaneni, A. (2025). Estimated glomerular filtration rate, albuminuria, and risk of infection: a collaborative meta-analysis of individual participant data. EClinicalMedicine, 86(103372), 103372.https://doi.org/10.1016/j.eclinm.2025.103372•
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Researchers have found in a global study of over 63,000 pregnant women that low free thyroxine (FT4) levels and isolated hypothyroxinaemia are linked to a higher risk of gestational diabetes. Contrary to prior assumptions, subclinical hypothyroidism showed no significant association, suggesting that universal screening and treatment for it may not reduce gestational diabetes risk.
Pregnancy is a state of increased metabolic demand that necessitates major changes in endocrine physiology. Gestational thyroid dysfunction and gestational diabetes are common endocrine conditions of pregnancy that frequently coincide. Although the effects of thyroid hormones on glucose metabolism are well documented, important knowledge gaps remain in terms of the extent and clinical relevance of these effects during pregnancy.
The aim of this meta-analysis is to assess the association of thyroid function test results with gestational diabetes and markers of glucose metabolism. In this systematic review and individual participant data meta-analysis, we searched Ovid MEDLINE, EMBASE, and Web of Science from database inception to Dec 12, 2024, for prospective population-based cohort studies with individual patient data on thyroid function, gestational diabetes, and measures of glucose homoeostasis during pregnancy. Furthermore, open invitations to join the Consortium on Thyroid and Pregnancy were issued to identify unpublished datasets. We excluded participants with multiple pregnancies; pre-existing thyroid disease or diabetes; current use of medications that could affect thyroid or glucose levels; or a history of infertility treatment, miscarriage, or stillbirth.
Exposures were maternal gestational concentrations of thyroid-stimulating hormone (TSH), free T4 (FT4), free T3 (FT3), and total T3; thyroperoxidase antibody positivity; thyroglobulin antibody positivity; and thyroid disease entities (ie, subclinical hypothyroidism, overt and subclinical hyperthyroidism, and isolated hypothyroxinaemia), which were defined according to current guidelines. The primary outcome was presence of gestational diabetes as defined in individual cohorts. Individual participant data were analysed using generalised linear mixed-effects regression models adjusting for maternal age, BMI, smoking status, parity, ethnicity, fetal sex, and gestational age at blood sampling.
They identified 638 published studies with our systematic search, of which 21 studies based on 17 cohorts met inclusion criteria; 11 of these prospective cohort studies provided individual participant data, and data from an additional 14 cohorts were added via personal contacts and open invitations, resulting in a study population of 63 548 participants from 25 cohorts after exclusions. Of the 52 632 participants in 17 cohorts with TPOAb measurements available to define thyroid disease entities, 1687 (3·2%) of these participants had subclinical hypothyroidism, 1153 (2·2%) had isolated hypothyroxinaemia, and 2958 (4·7%) had gestational diabetes. Compared with euthyroidism, isolated hypothyroxinaemia was associated with a higher risk of gestational diabetes (absolute risk 6·5% [72 of 1113] for isolated hypothyroxinaemia vs 3·5% [1555 of 44 787] for euthyroidism; adjusted odds ratio [aOR] 1·52 [95% CI 1·17–1·98], p=0·0017; 45 900 participants).
A lower FT4 concentration was associated with a higher risk of gestational diabetes (non-linear, p<0·0001). A higher risk of gestational diabetes was found both with a higher FT3 concentration (aOR 1·18 [95%CI 1·10−1·28], p<0·0001) and with a higher FT3-to-FT4 ratio (non-linear; p<0·0001). No evidence was found of associations of TSH, thyroid antibodies, or other thyroid function test abnormalities with gestational diabetes. I2 statistics for the primary analyses ranged from 0–43%, indicating low to moderate heterogeneity.
The funnel plot for overt hyperthyroidism indicated a possibility for publication bias (p=0·049), but funnel plots for all other variables did not. A lower FT4 concentration and isolated hypothyroxinaemia during pregnancy are associated with a higher risk of gestational diabetes. Our results challenge the long-standing notion that subclinical hypothyroidism or thyroid autoimmunity are risk factors for gestational diabetes and support both the risk profile for gestational thyroid dysfunction and ongoing efforts on optimisation of treatment targets for pregnant people taking levothyroxine. Follow-up studies are required to establish to what extent levothyroxine initiation or dose adjustments can affect insulin resistance and antihyperglycaemic therapies during pregnancy.
Reference:
Association of gestational thyroid function and thyroid autoimmunity with gestational diabetes: a systematic review and individual participant meta-analysis. Osinga, Joris A J et al. The Lancet Diabetes & Endocrinology, Volume 0, Issue 0
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A new study published in Clinical Infectious Diseases highlights the potential of pemivibart, a long-acting monoclonal antibody, as a preventive therapy for COVID-19. Researchers evaluated the safety and efficacy of pemivibart in a phase 3 randomized controlled trial involving uninfected adults who were at increased risk of SARS-CoV-2 exposure.
The results showed that a single intramuscular dose of pemivibart significantly reduced the risk of symptomatic COVID-19 over a follow-up period of several months.
The antibody was well tolerated by participants, with adverse events comparable to those observed in the placebo group. Importantly, the study noted that the protective effects were maintained even as new variants of the virus circulated, underscoring the potential for pemivibart to serve as a robust option for pre-exposure prophylaxis-especially among immunocompromised individuals or those for whom vaccination offers limited protection.
Given the waning immunity from vaccines over time and ongoing concerns about breakthrough infections, especially in high-risk groups, long-acting antibodies like pemivibart may fill a critical gap in COVID-19 prevention strategies.
The authors of the study emphasize that further real-world effectiveness data and ongoing surveillance of viral mutations are needed to confirm its broad utility, but early results are encouraging. If approved for wider use, pemivibart could be integrated into preventive care protocols for vulnerable populations, including transplant recipients, cancer patients undergoing chemotherapy, and others with compromised immune systems.
The study adds to a growing body of evidence supporting antibody-based prophylaxis as a complement to vaccination efforts in controlling the COVID-19 pandemic.
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Patients who develop alcohol withdrawal syndrome (AWS) after major surgery face significantly higher risks of complications, longer hospital stays, and increased health care costs, according to a study published in the Journal of the American College of Surgeons (JACS).
The findings underscore the need for screening before surgery and targeted interventions.
Using the National Inpatient Sample (2016–2019), researchers analyzed data from 3 million adults who underwent major operations, including colectomy, cardiac surgery, and liver resection. Among them, 16,504 (0.5%) were diagnosed with AWS, including 6,591 (0.2%) with life-threatening delirium tremens (DT). DT is a severe form of alcohol withdrawal that can include shaking, confusion, and hallucinations.
“AWS is a preventable complication, yet it’s often overlooked in surgical planning,” said lead author Timothy M. Pawlik, MD, PhD, MPH, FACS, surgeon-in-chief at the Ohio State University Wexner Medical Center. “Our study shows that proactive screening and multidisciplinary care — involving surgeons, social workers, and addiction specialists — can save lives and reduce costs.”
Key Findings
High-risk patients: AWS was more common in men (median age 61), Medicaid recipients, and those with substance use disorders.
Complications: AWS doubled the risk of respiratory failure and sepsis. DT increased mortality by 40%.
Economic impact: Adjusted hospitalization costs rose by $10,030 per patient with AWS; DT added another $5,300.
Interventions for the Future
The study highlights actionable strategies to improve outcomes:
Preoperative screening: Use validated tools (e.g., AUDIT-C) to identify high-risk patients.
Judgment-free care: “This is a disease, not a moral failing,” stressed Dr. Pawlik. “We need honest conversations to tailor treatment.”
Early intervention: For patients at risk, preventative medications (e.g., benzodiazepines) and ICU-level monitoring may prevent DT.
“A patient recovering from major surgery shouldn’t also battle withdrawal,” said Dr. Pawlik, recalling a case where AWS led to aspiration pneumonia post-surgery. “We can change this by addressing alcohol use before surgery and ensuring safer recovery environments.”
Limtations: The study relied on administrative data, potentially underestimating AWS incidence. Long-term outcomes and treatment specifics (e.g., benzodiazepine use) were not assessed.
Coauthors are Azza Sarfraz, MBBS; Areesh Mevawalla MD; Abdullah Altaf, MD; Mujtaba Khalil, MD; Zayed Rashid, MD; Shahzaib Zindani MD
The study is published as an article in press on the JACS website.
Citation: Nationwide Trends and Perioperative Outcomes of Alcohol Withdrawal Syndrome After Major Operation. Journal of the American College of Surgeons. DOI: 10.1097/XCS.0000000000001487
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A new study published in PeerJ has found that turmeric causes the most significant discoloration in dental resin-based composites (RBCs) compared to coffee and kombucha, with single-shade RBCs exhibiting poorer color stability than multi-shade composites. Researchers tested 60 composite specimens using two types of materials: a single-shade RBC with an advanced polymerization system (APS) (Vittra APS Unique, FGM Dental Group, Brazil) and a conventional multi-shade universal RBC (Tetric N-Ceram, Ivoclar Vivadent, Germany). Each group was subdivided and immersed in turmeric, coffee, or kombucha for 12 days, and color changes (ΔE*ab and ΔE00) were measured at baseline, day 6, and day 12. Results showed that turmeric caused the highest degree of discoloration (p < 0.001), followed by coffee and then kombucha. Additionally, the universal RBC demonstrated significantly better resistance to staining compared to the single-shade APS-based composite (p = 0.004). Researchers concluded that time, staining medium, and material type all significantly influenced color changes (p = 0.005 for three-way interaction). These findings highlight a potential esthetic limitation of single-shade composites, particularly when patients consume beverages or foods containing strong chromogens like turmeric. While turmeric’s staining potential was already well-documented on natural teeth, this study adds valuable evidence of its impact on modern composite resins, especially those marketed for universal shade-matching convenience. Clinicians may need to consider this when selecting materials for patients with high exposure to staining agents. The authors recommend further long-term studies to confirm these results and to evaluate whether surface finishing, polishing, and sealing techniques can mitigate discoloration over time. This study underscores the importance of patient education regarding dietary habits and the impact of staining beverages on restorative esthetics, especially for those seeking long-lasting cosmetic results.
Keywords: resin-based composites, color stability, turmeric staining, single-shade composites, universal RBC, PeerJ, Vittra APS Unique, Tetric N-Ceram, Yeslam & Bakhsh, dental esthetics
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