Oral ulcer is one of the most prevalent oral disorders, and is characterized by a high tendency to recur. Quercetin, a naturally occurring flavonoid, possesses antioxidant and anti-inflammatory properties. However, the mechanisms underlying the therapeutic effects against oral ulcer remain unclear. To address this issue, the present study employed an integrated approach combining network pharmacology prediction and in vivo experimental validation to investigate this issue. Network pharmacology analyses identified 167 intersecting targets between quercetin and oral ulcer. Molecular docking revealed favorable binding affinities of quercetin for multiple core targets. In vivo studies using a rat model of oral ulcer demonstrated that quercetin significantly reduced the ulcer area, ameliorated ulcer severity, decreased the serum levels of pro-inflammatory cytokines, and downregulated the expression of phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt). Collectively, these findings suggest that quercetin may exert its therapeutic effects against oral ulcer through modulation of the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, thereby providing experimental evidence to support its potential clinical application.
To evaluate the efficacy and safety of oral PCSK9 inhibitors in adults with hypercholesterolemia by synthesizing evidence from randomised controlled trials. This systematic review and meta-analysis followed PRISMA guidelines and was registered on PROSPERO (CRD420261303350). PubMed, Embase and Scopus were searched from inception to March 2026 for randomised controlled trials comparing oral PCSK9 inhibitors with placebo in adults with hypercholesterolemia. Primary outcomes were changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides. Secondary outcomes included other lipid parameters, adverse events and mortality. Random-effects models were used to calculate mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI). Quality of the included studies was assessed using the RoB2 tool and certainty of evidence was assessed using the GRADE approach. Five randomised controlled trials (n = 4268) were included. Oral PCSK9 inhibitors significantly reduced LDL-C (MD -49.49 mg/dL; 95% CI -54.81 to -44.18; p < 0.00001) and triglycerides (MD -11.65 mg/dL; 95% CI -15.53 to -7.78; p < 0.00001). Significant reductions were also observed in non-HDL cholesterol, apolipoprotein B, lipoprotein(a) and total cholesterol. Dose-dependent effects were noted, with greater reductions at higher doses. No significant differences were observed in mortality or overall adverse events. Treatment discontinuation due to adverse events was lower with intervention. Oral PCSK9 inhibitors were associated with clinically meaningful improvements in multiple lipid parameters while maintaining a favourable short-term safety profile. However, the available evidence is derived primarily from short-term randomised trials evaluating surrogate lipid outcomes. Larger randomised trials with longer follow-up and cardiovascular outcome data are needed to better define the long-term clinical role of oral PCSK9 inhibitors.
Oral cavity severe dysplasia/carcinoma in situ (CIS) represents a management conundrum. The rate of malignant progression, comparative effectiveness of treatment approaches, and prognosis are poorly defined. Existing data support resection, ablation, or surveillance. Such conflicting reports lead to undertreatment/overtreatment of a controversial condition. We investigate severe dysplasia treatment patterns and outcomes. U.S. cancer registry data (2004-2021) were used to analyze severe dysplasia and oral cavity carcinoma. Cases with regional or distant metastases were excluded. Multivariable Cox regression models were constructed to determine associations between covariates and overall survival (OS). Overall, 3,502 TisN0 cases and 42,887 T1-T4N0 cases were identified across 1298 institutions (Tis (7.5%), T1 (41.9%), T2 (25.0%), T3 (9.6%), T4 (16.0%)). On univariate analysis, higher T-classification correlated with poorer outcomes (10-yr OS: Tis (60.6%), T1 (56.6%), T2 (46.1%), T3 (40.1%), T4 (32.9%)) (p < 0.001). Tis cases undergoing wide resection performed better than those with local excision/ablation (10 yr OS: 62.4% vs. 58.8%, p = 0.01). Tis cases resected with negative margins performed better than those with positive margins or under observation (10 yr OS: 61.6% vs. 55.7% vs. 52.1%, p = 0.02). On multivariable analysis, positive margins (HR 1.21 [95% CI 0.98-1.50], p = 0.008), observation (HR 1.06 [95% CI 0.80-1.40], p = 0.007), and local excision/ablation (HR 1.08 [95% CI 0.94-1.24], p = 0.006) were associated with worse OS. Landmark analysis at one year confirmed these results. Large-scale, long-term analysis supports that severe dysplasia outcomes perform similarly to that of early-stage oral cavity malignancy, with inferior outcomes when undertreated. Definitive resection with negative margins appears predictive of improved mortality risk.
Gut microbial metabolites play crucial roles in regulating systemic immunity, but their mechanisms and limited drug-like properties remain unresolved. Here we report an oral nano-formulation that leverages gut microbial metabolites to modulate T cell metabolism and amplify antitumour immunity. Through an in vitro screening of gut microbial metabolites, we identified 3,4-dihydroxybenzoic acid that improved adoptive T cell therapy and enhanced CD8+ T cell stemness by suppressing glycolysis and regulating the Akt-mTORC1-Myc pathway. To harness the potency of 3,4-dihydroxybenzoic acid for systemic cancer immunotherapy, we engineered a 3,4-dihydroxybenzoic acid prodrug nano-emulsion, significantly increasing its oral absorption and half-life. In multiple murine tumour models, the oral nano-emulsion enhanced the expansion of antigen-specific, stem-like CD8+ T cells, sensitizing tumours to anti-PD-1 blockade and exerting robust antitumour efficacy. By integrating nanotechnology with microbial-metabolite-based immunotherapy, this study establishes a mechanistic link between the gut microbiota and T cell immunity, offering a promising approach for cancer immunotherapy.
This study aimed to evaluate the predictive value of a quantitative index measuring the extent of somatic copy-number alteration (SCNA) for malignant transformation (MT) in oral leukoplakia (OLK). A prospective cohort of 122 patients with OLK was followed for a median of 74 months. Whole-exome sequencing (WES) was performed on fresh-frozen tissue specimens. SCNA-L was defined as the total autosomal length of segments exceeding predefined copy-number and minimum-width thresholds. The cohort was stratified into high- and low-SCNA-L groups using a median cutoff of 3.3. The primary outcome was MT to oral squamous cell carcinoma (OSCC). Statistical analyses included Kaplan-Meier survival analysis, Cox proportional hazards models, time-dependent ROC curves, a 1,000-resample bootstrap optimism-corrected C-index, and bootstrap internal validation using calibration curves. The MT rate was significantly higher in the high-SCNA-L group (26.7%) than in the low-SCNA-L group (6.5%; P < 0.01). SCNA-L remained an independent predictor of MT in the multivariable analysis (hazard ratio = 4.684, P = 0.006). The predictive model, incorporating SCNA-L and lesion type, demonstrated adequate discrimination and satisfactory calibration for mid-term prediction. As an independent predictor of MT in OLK, the quantitative index SCNA-L can serve as a molecular supplement to conventional pathological grading.
To investigate somatic mutations in the whole genes of tissue samples from patients with oral leukoplakia (OLK), as the most typical precursor of oral cancer; and identify the specific genes as a mutational panel for predicting OLK malignant transformation. A total of 123 consecutive OLK patients with long-term follow-up (median, 73 months) were prospectively enrolled, and divided into training set (n = 92) and independent test set (n = 31) based on chronological order of enrollment. Genomic DNA was isolated from the fresh-frozen biopsy tissues and somatic mutations in all genes were measured by whole-exome sequencing. We constructed a 3-gene (TP53, CASP8, and CYP2B6) mutational panel for risk stratification (any mutation vs. no mutation) of OLK malignant transformation. Kaplan-Meier analysis showed that the prognostic power of the 3-gene panel (log-rank P < 0.0001) for risk stratification in malignant progression was better than that of pathological grade in the training and test set, respectively. Multivariate Cox regression analysis revealed that this panel was an independent variable significantly associated with progression in the training (hazard ratio [HR] = 8.05; P < 0.001) and test set (HR = 11.26; P = 0.0421), respectively. The area under the curve (AUC) with 95 % confidence interval was 0.770 (0.648-0.892) and 0.877 (0.705-1.000) in the training and test set, respectively, for predicting malignant transformation in OLK patients. We established a 3-gene (TP53, CASP8, and CYP2B6) mutational panel as risk stratification model could effectively predict OLK malignant transformation, outperforming pathological grading-based assessment. Such genetic markers may provide a foundation for developing personalized management strategies.
Whether direct oral anticoagulants (DOACs) are a safe and effective alternative to warfarin in patients with atrial fibrillation and mitral stenosis (AF-MS) remains controversial. To evaluate the effectiveness and safety of DOACs versus warfarin in patients with AF-MS. Observational cohort study using target trial emulation. Population-wide insurance claims data in Taiwan. Patients diagnosed with AF-MS and prescribed either DOACs or warfarin between 1 January 2011 and 31 December 2021 were included in the study. DOACs or warfarin. Absolute risk differences (RDs) and risk ratios (RRs) at 1 year and 5 years of follow-up for ischemic stroke, systemic embolism, composite stroke, myocardial infarction (MI), intracranial hemorrhage, gastrointestinal bleeding, bleeding at other critical sites, and all-cause death. Compared with warfarin, DOACs were associated with an increased risk for ischemic stroke (RD, 4.97 percentage points [95% CI, 1.27 to 8.57 percentage points]; RR, 1.22 [CI, 1.05 to 1.41]) and composite stroke (RD, 5.56 percentage points [CI, 1.77 to 8.97 percentage points]; RR, 1.23 [CI, 1.07 to 1.42]) and a decreased risk for MI (RD, -1.61 percentage points [CI, -3.17 to -0.03 percentage points]; RR, 0.61 [CI, 0.37 to 0.99]) at the 1-year follow-up. Rivaroxaban increased the risk for ischemic stroke during both short- and long-term follow-up periods. The 2 groups did not differ in risks for bleeding or all-cause death. Limited sample size, lack of detailed information on MS severity, and lack of international normalized ratio measurements. In Asian patients with AF-MS, DOACs were associated with an increased 1-year risk for stroke but a decreased risk for MI compared with warfarin. Research Grants Council of Hong Kong.
Tumour budding (TB) is known as a histopathological parameter defined as single tumour cells or clusters of up to 4 cells at the tumour invasion front (TIF) (TB score 1: 0-4 buds, TB score 2: 5-9 buds, TB score 3: ≥10 buds). However, conventional assessment based on a single section may not capture heterogeneity within the TIF. Therefore, this study applied a novel quantitative approach (TB rel), in which all available sections were evaluated and summarized as an average score. 256 patients with oral squamous cell carcinomas (OSCC) were included and 1289 haematoxylin and eosin-stained sections were analysed. Based on TB rel, patients were stratified into prognostic clusters: Cluster C1 (TB rel = 1.0) and cluster C2 (TB rel >1.0). Increased TB rel was associated with adverse histopathological features reflecting tumour aggression. In clinically node-negative patients (cN0), TB rel identified occult lymph node metastasis (pN+) with an odds ratio of 6.32. Furthermore, patients with higher TB rel showed a higher risk of poorer overall disease progression and survival compared to patients having consistently low TB scores along the TIF. Given its prognostic relevance, TB rel should be integrated into routine diagnostics. This may support more individualized indication for neck dissections.
Cannabigerol (CBG) is a minor cannabinoid that has been considered as a potential therapeutic, yet basic acute pharmacodynamics and pharmacokinetics across commercially available doses have not been examined. To complete this critical step, healthy adults (n = 12) were enrolled in a single ascending dose human laboratory study where they consumed 0, 25, 50, 100, and 200 mg of CBG isolate suspended in medium-chain triglyceride oil. The placebo administration occurred randomly within the dosing sequence. Standardizing flavor and solution volume facilitated blinding. Adverse events were recorded throughout to characterize safety and tolerability. Pharmacodynamic outcomes (ie, subjective, cognitive, and physiological responses) and plasma samples were collected at baseline and regular intervals after drug administration (0.5-, 1-, 1.5-, 2-, 3-, 4- , 5-, 6-, and 8-hours). Pharmacokinetic parameters (eg, peak plasma CBG concentration) were also measured. Liver function tests were characterized at baseline and after acute administration of the 2 highest doses. No drug-related adverse events occurred. Subjective effects associated with CBG administration were minimal with the exception of significant decreases in self-reported ratings of Jittery and Active associated with 50 mg, significant decreases in Calm associated with 100 mg, and increases in Appetite associated with 200 mg of CBG. Pharmacokinetics were dose-orderly, but significant individual variability was observed. Liver function tests never exceeded the upper limit of normal following acute administration of the highest doses. Overall CBG was well-tolerated with no robust pharmacodynamic effects; chronic dosing studies are needed to more fully characterize the safety and pharmacodynamic profile of oral CBG. SIGNIFICANCE STATEMENT: Cannabigerol has garnered attention as a potential therapeutic for many diagnoses before the fundamental studies investigating its pharmacokinetics and pharmacodynamics have been completed. We aimed to provide this information through a single ascending dose study, finding that cannabigerol is well-tolerated while yielding few pharmacodynamic or psychoactive effects.
In distal extension cases involving multiple missing teeth planned to be restored with implant-supported fixed prostheses, the accuracy of digital recording the maximum intercuspation position (MIP) using intraoral scanners (IOS) remains insufficient. This in vitro study aimed to evaluate the effect of a novel developed bite registration cap on the accuracy of digital MIP recording by IOS in distal extension cases with different edentulous span lengths. A series of prefabricated bite registration caps was designed to be retained on the top of the healing abutments. Three pairs of reference stone casts containing implant analogs and representing different edentulous conditions (2,3 and 4 missing teeth), were mounted on a mechanical articulator. Two groups were created based on the landmarks used for bite registration: bite registration caps (test group) and healing abutments (control group). Each group was further divided into 3 subgroups based on edentulous span length (2, 3, or 4 missing teeth). In each subgroup, the casts were digitized with an IOS, and the scan datasets were duplicated 10 times and articulated by buccal bite registrations (n=10). Maxillary occlusal surface deviations and linear distance deviations between interarch markers were calculated to evaluate the accuracy of MIP recording. Two-way ANOVA with Tukey post hoc tests was used to analyze maxillary occlusal surface deviations (α=.05). The linear distance deviations were compared by Mann-Whitney U test and Kruskal-Wallis test (α=.05). Both the registration method and edentulous span length significantly affected the trueness of MIP recording, with a significant interaction between these 2 factors (P<.001). For cases with 2, 3, and 4 missing teeth, the maxillary occlusal surface deviations in the test and control groups were 55.5 ± 6.7 μm vs 71.4 ± 10.4 μm, 56.6 ± 3.0 μm vs 78.0 ± 8.0 μm, and 56.1 ± 3.5 μm vs 171.5 ± 10.3 μm, respectively. Across all edentulous conditions, maxillary occlusal surface deviations in the test group were significantly lower than those in the control group (P<.001). In the control group, the maxillary occlusal surface deviations were significantly greater in distal extension conditions with 4 missing teeth than in those with 2 or 3 missing teeth (P<.001). From the second premolar to the second molar, the absolute values of the linear distance deviations were significantly higher in the control group than in the test group (P<.01). Compared with the control group, the use of bite registration caps significantly reduced the maxillary occlusal surface deviations and linear distance deviations, thereby improving the trueness of digital MIP recording in distal extension cases restored with implant-supported fixed prostheses. Notably, the trueness was clinically unacceptable in distal extension cases with four missing teeth without the use of bite registration caps. These findings suggest that under in vitro conditions, the bite registration caps can enhance the trueness of IOS-based MIP recording in distal extension cases restoring with implant-supported fixed prostheses. The application of the novel bite registration caps improved the trueness of digital MIP recording by IOS in distal extension cases restoring with implant-supported fixed prostheses.
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Urinary tract infections (UTIs) are a common indication for Outpatient Parenteral Antimicrobial Therapy (OPAT) and often involved prolonged intravenous (IV) treatments. A theory-informed Antimicrobial Stewardship (AMS) intervention was implemented to optimize antibiotic duration and promote IV-to-oral switching in OPAT patients with UTIs. This pre-post quasi-experimental single-center study included adults with UTIs managed through OPAT. The intervention was designed using behaviour change techniques, and structured as a bundle of quality improvement strategies to optimize antibiotic prescribing. [1] the proportion of patients receiving appropriate treatment duration and [2] the proportion of those with microbiological confirmation and an oral option, who were switched to oral. adverse events, 90-day recurrence and readmission, healthcare resource consumption. 314 patients were included. Post-intervention patients were more often male, and with a history of recurrent UTI. Other baseline characteristics were comparable. Appropriate antibiotic duration increased from 44.4% (baseline) to 83.3% (intervention period) (p≤0.001), IV-to-oral switch rates from 62.8% to 85.7% (p≤0.001). In adjusted analyses, the intervention was independently associated with appropriate duration (OR 6.70, 95% CI 3.79-11.85), IV-to-oral switching (OR 3.57, 95% CI 1.56-8.19), fewer 90-days UTI recurrences (OR 0.41, 95% CI 0.21-0.80) and no increase in 90-days readmissions. A significant reduction in healthcare cost was achieved with a median difference of -648.8€ (95% CI -1050.0 to -247.7). A structured AMS intervention for UTIs in OPAT improved appropriate antibiotic duration, increased IV-to-oral switching, and reduced healthcare costs without compromising clinical safety. Behavior-informed stewardship strategies can optimize antimicrobial use in OPAT care.
Preterm birth is the leading cause of mortality in children globally under the age of 5 years. A universal, daily necessity, nutrition has potential for intervention to modulate preterm birth risk. This scoping review aimed to synthesize evidence on nutrition as an interventional tool to reduce preterm birth risk. PubMed, CINAHL, Web of Science, Cochrane database, EMBASE and Google Scholar were searched for relevant studies published between the years of 2000-2023. Inclusion criteria were human pregnancy populations with dietary intervention with intent of modulating preterm birth risk. Original research articles, cohort studies, cross-sectional studies and randomized control trials were included and papers with results not yet reported, non-original research articles and exposure or intervention not reported were excluded. For this scoping review, databases were searched using the Problem, Concept, Context (PCC) framework (Problem: Spontaneous preterm birth; Concept: nutrition; Context: Antenatal period). Data was analyzed, risk of bias assessed, and evidence was summarized based on results. From 1,664 citations, data were extracted from 74 studies. Studies were divided into three categories and below recommendations are presented from results: 1) Micronutrient recommendations (15 studies): Iron 60mg oral, folic acid 0.4mg oral daily and daily multiple micronutrient supplement have strong evidence as protective factors against preterm birth. 2) Macronutrient recommendations (24 studies): docosahexaenoic acid supplementation >800mg oral daily throughout pregnancy, most importantly, from the second trimester to delivery and moderate fish intake of ∼3 servings weekly has strong evidence as protective against preterm birth. 3) Specific-diet recommendations (35 studies): Diets high in fruits, vegetables, oils, whole grain cereals and fiber, adherence to the Mediterranean diet and avoidance of the Western diet demonstrate decreased preterm birth risk. Nutrition plays an important role in preterm birth. Synthesis of evidence on dietary behavior is useful for women, their healthcare providers, alongside the legislators and regulatory bodies that support them.
IgE-mediated food allergy and eosinophilic esophagitis (EoE) represent distinct yet interconnected manifestations of food-induced immune dysregulation. Rather than separate entities, emerging evidence supports a model that is on a continuum, in which clinical phenotypes are determined by antigen exposure patterns, dose, chronicity, and individual immune responses. This relationship has critical implications for food allergy immunotherapy, particularly oral immunotherapy. Among children with IgE-mediated food allergy, EoE prevalence is nearly 100-fold higher than the general population at 4.7%. During oral immunotherapy, gastrointestinal symptoms are common, with confirmed EoE developing in 1% to 10% of participants. Mechanistically, antigen avoidance favors IgE-mediated responses through T follicular helper cells, whereas sustained exposure promotes TH2-driven esophageal inflammation via pathogenic effector TH2 cells. Regulatory T-cell dysfunction appears central to this phenotypic switching. Clinical management requires risk stratification, systematic monitoring strategies, and individualized protocols that balance desensitization benefits against esophageal inflammation risks. Future directions include noninvasive diagnostic biomarkers, biologic therapies, and evidence-based prevention strategies. Understanding the food allergy-EoE continuum is essential for optimizing safety and efficacy of food allergen immunotherapy while minimizing complications.
To describe the clinical characteristics and dental treatment for patients treated at a dental hospital in the United Kingdom. This descriptive study utilized anonymized routinely collected electronic health record data from dental patients who attended Leeds Dental Institute, collected from 2014 to 2023. Patient characteristics, comorbidities and completion of dental treatment were reported through descriptive statistics (mean and standard deviation [SD]; percentage) and by clinic attended. A total of 109,718 patients were included in this study, of whom 58,964 (54%) were female, and 43,828 (40%) lived in the most deprived areas in England. The most frequently recorded comorbidities were joint or bone problems (n = 4913, 5%), chest or breathing problems (n = 4619, 4%), and heart problems (n = 4455, 4%). Across clinic groups, the proportion of patients with at least one recorded comorbidity was highest among those attending periodontal/restorative clinics (24%) and acute dental care clinics (19%). Less than half of all patients (n = 52,655, 48%) completed their dental treatment. Oral surgery had the highest percentage of patients who completed their treatment (n = 10,459, 71%). The sociodemographic and clinical characteristics reported in this study reflect a large population of dental patients from Leeds and the surrounding region. The findings of this study are consistent with literature showing sociodemographic trends in dental attendance. Future linkage of dental electronic health records with hospital records could improve understanding of the complexities of oral-systemic associations further.
To compare the cost, time-efficiency, and cost-effectiveness of conventional complete dentures (CDs) and 3D-printed dentures (DDs). Twenty-three edentulous patients (mean age: 65.96± 8.74) participated in this clinic study. Each participant received two complete dentures fabricated using conventional 5-visit workflow (CD), and a 3-visit digital technique (DD). Clinical and laboratory times were recorded for all fabrication steps, including impressions, jaw relations, try-in, insertion and denture processing. Cost analysis was conducted from the provider perspective and included material costs based on purchase prices and labor costs estimated from recorded procedure times and the corresponding reference fee schedules for clinicians and dental technicians. Cost-effectiveness was assessed using overall patient satisfaction and Oral-Health-related Quality of Life (OHRQoL) as effectiveness indicators to calculate the incremental cost-effectiveness ratio (ICER). Costs of conventional dentures (429.40 (421.44-439.73)) were statistically higher (P<0.001) compared to denture fabricated using digital workflow (276.94 (269.79-287.92)). Patient overall satisfaction and OHRQoL did not differ between the techniques (P>0.05). The digital dentures required significantly reduced clinical (90.50 min vs. 179.68 min; P<0.001) and laboratory (150.85 min vs. 562.98 min; P<0.001) times, respectively. Monte Carlo simulations indicated the digital workflow was more cost-efficient and cost-effective, since CD had lower NMB and negative ICER for all analyses. In a university setting, DDs are a resource-efficient option that optimizes clinical and laboratory time by significantly reducing the overall costs. Therefore, this approach may be a cost-effective strategy with economic advantages, while maintaining patient-reported outcomes comparable to those achieved with CDs. 3D-printed complete dentures substantially reduce clinical and laboratory time, lower overall costs, and offer a cost-effective alternative to conventional dentures without compromising patient satisfaction or oral-health-related quality of life. REBEC - 2c96zr3.
Comparative effectiveness of exercise modalities across skeletal sites and the dose-response pattern for bone mineral density (BMD) remain incompletely characterized. This review aimed to compare exercise modalities across six skeletal sites and to explore whether MET-min/week could describe a dose-response relationship between exercise exposure and BMD change. We conducted a systematic review and meta-analysis of RCTs (PROSPERO: CRD420261345811), searching four databases to March 2026. Three complementary frameworks were applied: three-level pairwise meta-analysis with robust variance estimation, Bayesian network meta-analysis (NMA) with prespecified vague priors and SUCRA rankings, and exploratory dose-response model-based NMA using restricted cubic spline modelling of MET-min/week. Methodological quality was assessed using ROBUST-RCT, GRADE, and an NMA-specific certainty assessment considering intransitivity and incoherence. We included 162 RCTs (10,475 participants; age range, 18-81.6 years). Pairwise GRADE certainty ranged from high (femoral neck) to very low (total hip). Significant pooled effects were observed at five of six sites: lumbar spine (Hedges' g = 0.22), femoral neck (g = 0.28), Ward's triangle (g = 0.23), trochanter (g = 0.15), and total body (g = 0.26). NMA suggested site-specific ranking patterns, but credible intervals were often wide and NMA certainty was commonly limited by imprecision, heterogeneity, and sparse direct evidence. Dose-response analyses suggested an overall peak near 1100 MET-min/week for lumbar spine BMD, but agent-specific optima, especially AT+RT at 1800 MET-min/week, were boundary-sensitive and exploratory. Exercise is associated with small-to-moderate, site-specific improvements in BMD across adulthood. Modality rankings and dose-response estimates should be interpreted as hypothesis-generating rather than definitive prescriptions, particularly where direct evidence was sparse or certainty was low.
This paper aims to describe the treatment patterns of contemporary systemic menopausal hormone therapy (MHT) in Denmark. This study is a nationwide drug utilization study including an open cohort of all Danish women aged >40 years between 2000-2024. This study analysed the use of systemic MHT, identified by prescription redemption and categorized by route of administration. During the study period, n = 2 350 335 women reached the age of >40 years and n = 454 592 (19.3%) women used MHT at least once. The prevalence declined from 107.7 per 1000 women in the total cohort on 1 January 2000, to 17.8 per 1000 women on 1 January 2024. The corresponding prevalences for the age group 51-60 years decreased from 191.0 per 1000 women to 33.8 per 1000 women during the same period. The incidence declined from 15.7 per 1000 person-years in 2000 to 4.3 per 1000 person-years in 2023 and then increased to 8.5 per 1000 person-years in 2024. The corresponding numbers for the age group 51-60 years were 33.9 per 1000 person-years in 2000, 9.3 per 1000 person-years in 2023, and 20.2 per 1000 person-years in 2024. In 2022-2024 more women initiated transdermal (2022: 56%; 2023: 63%; 2024: 75%) than oral therapy. For women who initiated treatment before 2015, the cumulative duration of use was often <1 year (37%). Prevalence and incidence of systemic MHT declined over time in Denmark, except in 2024 where the incidence increased. In recent years, more women started transdermal than oral therapy. Cumulative duration of use was often less than 1 year.