This randomized, double-blind, multicenter Phase III study evaluated the efficacy and safety profile of a single-pill triple combination of valsartan/amlodipine/chlorthalidone (KDF1901, Valdipine Plus) compared with a dual combination of valsartan/amlodipine (KDF1901-R) in patients with essential hypertension. Patients (n = 294) with inadequately controlled hypertension after a 4-week run-in phase with valsartan/amlodipine (80/5 mg) were randomized to receive KDF1901 (valsartan/amlodipine/chlorthalidone 160/10/25 mg, n = 147) or KDF1901-R (valsartan/amlodipine 160/10 mg, n = 147) for 8 weeks. The primary efficacy endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Secondary endpoints included changes in mean sitting diastolic blood pressure (MSDBP), BP normalization rates, and response rates. Safety profile outcomes assessed treatment-emergent adverse events (TEAEs), laboratory parameters, and serious adverse events. At week 8, the KDF1901 group exhibited a significantly greater reduction in MSSBP (-22.8 ± 1.0 mmHg) compared with the dual therapy group (-16.7 ± 1.0 mmHg, P < 0.0001). Similarly, the mean MSDBP reduction was significantly greater with KDF1901 (P = 0.0006). BP normalization rates (75.9% vs 54.5%, P < .0001) and response rates (73.8% vs 51.7%, P < 0.0001) were significantly higher in the triple combination group. Overall, the incidence of TEAEs was similar between groups (24.7% vs 21.5%, P = 0.5783), with mild cases of dizziness were most commonly reported. Exploratory ad hoc analyses showed statistically greater changes in sodium, potassium, and uric acid levels with triple therapy, but clinically meaningful extreme electrolyte abnormalities were rare in both groups, and the overall laboratory profile remained acceptable. This trial reported that the single-pill triple combination KDF1901 significantly improved BP control compared with dual therapy without compromising tolerability. NCT07116863.
Recurrent implantation failure (RIF) remains a major barrier to successful assisted reproductive technology, given the lack of effective, mechanism-informed interventions to enhance endometrial receptivity. Jiawei Shoutai Wan (pills) (JWSTW), a modified formulation of the classic Shoutai Pill (STP) used in reproductive medicine, has not been systematically evaluated in the treatment of RIF, and its bioactive components and molecular targets remain largely unclear. To determine whether JWSTW improves implantation competence and to identify the pathways associated with its effects. A mifepristone-induced embryo implantation dysfunction (EID) rat model was established to evaluate implantation outcomes, uterine histology, and markers of endometrial receptivity and vascular perfusion. Bulk uterine transcriptomics and peripheral blood serum untargeted metabolomics were integrated with liquid chromatography-tandem mass spectrometry (LC-MS) based component profiling, network pharmacology, multi-omics correlation analysis, uterine cavity microbiota profiling and structure-based computational analyses. Key pathway molecules were further assessed using targeted molecular experiments. A retrospective cohort of RIF patients undergoing assisted reproduction was analyzed for ultrasound-derived endometrial receptivity parameters before and after treatment. JWSTW administration improved implantation outcomes in EID rats, characterized by the upregulation of multiple receptivity- and perfusion-associated tissue markers. Integrated multi-omics analyses identified peroxisome proliferator-activated receptor (PPAR) signaling and lipid metabolism as significantly enriched pathways, supported by corresponding gene-metabolite correlations. Animal experiments using PPAR agonists (rosigitazone) and antagonists (T0070907) further confirmed that the PPAR pathway is a primary target of JWSTW. JWSTW was also associated with structured changes in the uterine cavity microbiota, with enriched taxa and predicted functions aligned with lipid metabolism related pathways. LC-MS/MS characterization identified sweroside and loganic acid as major circulating constituents, while computational analyses prioritized a PPAR-centered target network with favorable binding affinity and structural stability. In the retrospective RIF cohort (n = 100), JWSTW was associated with increased endometrial thickness and improved Doppler-derived perfusion indices. These results demonstrated that JWSTW enhances endometrial receptivity and promotes embryo implantation in RIF by modulating the PPAR-lipid metabolism axis and remodeling the uterine microbiota. Consequently, our study advances the pharmacodynamic understanding of JWSTW and deepens the comprehension of its underlying mechanistic basis in RIF. Furthermore, these findings provide an innovative Traditional Chinese Medicine-based treatment strategy, offering a promising therapeutic avenue for patients with RIF.
Lower extremity peripheral artery disease (PAD) is a chronic ischemic disorder primarily driven by atherosclerosis (AS) and characterized by endothelial injury, lipid deposition, inflammation, oxidative stress, and hemorheological abnormalities. From the perspective of traditional Chinese medicine (TCM), its pathogenesis is commonly interpreted within the concept of "Tuoju", in which blood stasis obstructs the collaterals/meridians and may coexist with qi deficiency, blood heat, or phlegm-dampness. Dahuang Zhechong Pill (DHZCP), first recorded in the Jingui Yaolue, is traditionally prescribed to remove blood stasis, clear heat, and resolve masses, while also supporting vital qi and nourishing yin, which conceptually aligns with TCM pattern differentiation in PAD. Preclinical studies and limited clinical reports suggest that DHZCP may be associated with multi-domain effects relevant to PAD pathophysiology, including endothelial-related readouts, lipid metabolism, inflammation, oxidative stress, and hemorheological parameters. Clinical studies (mostly small-sample trials) indicate that DHZCP may be associated with improvements in ankle-brachial index (ABI), lipid profiles, blood viscosity, and microcirculatory perfusion, particularly when used as an adjunct to acupuncture, blood-activating prescriptions, or conventional therapies, with generally favorable short-term safety signals. This review summarizes the traditional rationale and modern evidence on DHZCP for PAD, critically appraises the current evidence base and its limitations, and proposes priorities for future research to support standardized clinical use and potential international application. This article is a structured narrative review based on a predefined literature search and study selection strategy. In silico findings (e.g., network approaches and molecular docking) are treated as hypothesis-generating evidence and are clearly distinguished from in vitro/in vivo and clinical studies.
Jiannao Bushen Pill (JNBSP) is a traditional Chinese medicine (TCM) preparation used for nourishing the brain and kidney, tonifying qi and spleen, calming the mind, and improving memory. Clinically, it has been widely applied for the treatment of amnesia and cognitive decline; however, its pharmacodynamic material basis remains largely unclear. In the present study, an ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap-HRMS) strategy was established to systematically characterize the chemical constituents of JNBSP. A total of 181 compounds were identified, and their herbal origins were further assigned through comparison with the chemical profiles of the 25 individual medicinal materials comprising the formula. In addition, 40 prototype compounds absorbed into the bloodstream and 41 metabolites were tentatively characterized in rat plasma after oral administration of JNBSP. To further evaluate the in vivo exposure behavior of representative absorbed constituents, microdialysis sampling combined with ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry was employed to monitor the temporal concentration profiles of six prototype compounds. The results revealed comparable Tmax values but different systemic exposure levels and elimination characteristics among these constituents, suggesting potentially different temporal and quantitative contributions to the pharmacological effects of JNBSP. To the best of our knowledge, this is the first systematic study to integrate comprehensive chemical profiling, characterization of absorbed prototypes and metabolites, and dynamic in vivo monitoring of representative constituents for JNBSP. These findings provide an important foundation for subsequent pharmacokinetic-pharmacodynamic studies, target identification, and mechanistic investigations of JNBSP in the treatment of cognitive dysfunction.
Neuroinflammation, characterized by dysregulated activation of microglia, is a hallmark of Parkinson's disease (PD). Nevertheless, therapeutic strategies aimed at the mechanism of inflammation resolution remain limited. This study integrated PD clinical cohorts, MPTP-induced and miR-146a-induced mouse models, as well as LPS-stimulated and miR-146a-activated cell models. Combined with omics analysis, behavioral detection and molecular biology experiments, we systematically evaluated the anti-inflammatory protective effects of Wuzi Yanzong Pills (WYP). The active plant metabolites of WYP were identified using a combination of UHPLC-Q-Exactive-MS/MS, AP-SMALDI Orbitrap MSI, and pharmacokinetic analysis. In PD patients, WYP significantly improved motor dysfunction, inhibited pro-inflammatory cytokines, and elevated neurotransmitter levels. Exosomal miRNA sequencing analysis indicated that miR-146a-5p may serve as a biomarker for PD and is positively correlated with disease severity. Animal experiments further showed that WYP improved motor symptoms and neuroinflammation in MPTP- and miR-146a-induced PD mice models. A dual-luciferase reporter assay confirmed ubiquitin specific peptidase 3 (USP3) as a direct target gene of miR-146a-5p. In an LPS-activated BV2 microglial cell model, WYP intervention reduced the content of miR-146a-5p in cell-derived exosomes and mitigated their pro-inflammatory damaging effects on neuronal cells. Component analysis revealed that 16 plant metabolites in WYP can enter the bloodstream, among which 11 can cross into the brain. Notably, geniposidic acid, hyperoside, kaempferol, protocatechuic acid, and schisandrol A significantly suppressed the expression of pro-inflammatory factors in BV2 cells, suggesting that they may be the main active components underlying the anti-inflammatory effects of WYP. WYP improves PD by regulating the miR-146a-5p/USP3/NF-κB pathway. Meanwhile, the active plant metabolites of WYP have been identified. These findings provide experimental evidence for WYP as a potential therapeutic agent for PD.
Hypercholesterolemia imposes a growing cardiovascular burden in China, yet low-density lipoprotein cholesterol (LDL-C) target attainment remains low. The single-pill combination (SPC) of ezetimibe and atorvastatin (E/A SPC) was approved in China in 2023 and added to the National Reimbursement Drug List (NRDL) in 2024. Compared with free combination therapy (E/A FCT), E/A SPC may improve adherence and LDL-C reduction, but its economic value has not been assessed in the Chinese context. To evaluate the cost-effectiveness of E/A SPC versus E/A FCT in Chinese adults with hypercholesterolemia inadequately controlled on statin monotherapy, and to estimate the 5-year budget impact of E/A SPC adoption. An 11-state Markov model was developed from the Chinese healthcare system perspective, projecting 20-year costs and health outcomes in patients aged 69 years with uncontrolled LDL-C (>70 mg/dL) after statin therapy. Clinical efficacy inputs were derived from a large real-world German head-to-head study (n = 311,242). Subgroup analyses were conducted by age, sex, and cardiovascular risk. A 5-year budget impact analysis estimated the financial consequences of increasing E/A SPC uptake. Costs and outcomes were discounted at 5% annually. E/A SPC generated 0.06 additional quality-adjusted life years (QALYs) at an incremental cost of USD 250.12, yielding an incremental cost effectiveness ratio (ICER) of USD 4,070/QALY, well below the willingness-to-pay threshold of USD 14,423. The probability of cost-effectiveness was 91%. Subgroup analyses consistently favored E/A SPC, with the most favorable ICERs observed in very high-risk patients and middle-aged patients. Over 5 years, E/A SPC was associated with incremental drug spending of USD 372.5 million, partly offset by USD 292.0 million in avoided cardiovascular event costs. E/A SPC is a cost-effective strategy for Chinese adults with hypercholesterolemia inadequately controlled on statin monotherapy, supporting its NRDL inclusion. The study findings should be further validated using larger-scale real-world data from China.
Buyiniuxi pill (BYNX) is a classical traditional Chinese medicine (TCM) formula first recorded in Taiping Shenghui Fang (AD 992) and has been traditionally prescribed for hair loss and premature hair greying. Its constituent herbs remain relevant in contemporary ethnopharmacological practice for hair regeneration. This study aimed to evaluate the hair regrowth-promoting effects of BYNX in a dihydrotestosterone (DHT)-induced murine model of androgenetic alopecia (AGA) and to explore its potential molecular mechanisms. The chemical profile of the BYNX aqueous extract was characterized using UHPLC-Orbitrap-MS. Network pharmacology was used to explore potential targets and pathways associated with AGA. In vivo efficacy was assessed in a DHT-induced murine model following oral administration of BYNX at low or high doses. Hair regrowth was evaluated by hair length and hair coverage percentage, while histopathology, immunohistochemistry, ELISA, and RT-qPCR were performed to investigate underlying mechanisms. UHPLC-Orbitrap-MS analysis revealed a chemically complex profile of BYNX, and representative constituents were selected for subsequent network pharmacology analysis. Predicted targets were mainly enriched in inflammation-related biological processes and the PI3K-AKT signaling pathway. In vivo, BYNX significantly alleviated DHT-induced hair growth inhibition, as evidenced by increased hair length, improved hair coverage, and restoration of hair follicle morphology. These changes were accompanied by reduced IL-6 and IL-4 expression, enhanced activation of the AKT/BCL-2 signaling pathway, and increased Cyclin D1 and β-catenin expression in dorsal skin tissue. BYNX significantly promotes hair regrowth in a DHT-induced murine model of AGA. The hair-regenerative effects of BYNX were associated with modulation of inflammatory responses and activation of AKT/BCL-2-related survival signaling, suggesting a multi-target regulatory pattern consistent with its traditional ethnopharmacological use.
This Medical News article is an interview with Rita Kalyani, MD, MHS, the American Diabetes Association’s chief scientific and medical officer and a professor of medicine at Johns Hopkins University School of Medicine, about research presented at the organization’s annual Scientific Sessions.
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Informed consent is a cornerstone of patient autonomy, yet its implementation in medication abortion, especially in the context of rapidly expanding telehealth and online access, remains understudied. This study explores how informed consent is experienced by women who undergo medication abortion, focusing on the information they receive and the gaps they perceive. Using an exploratory sequential mixed methods design, we first conducted a thematic analysis of online narratives to examine how women described their experiences with information, support, and uncertainty. We then developed and administered a national survey informed by these findings to assess how women perceive the informed consent process. Thematic analysis of online narratives revealed four key patterns: women sought information about medication abortion symptoms and side effects; emotional support; urgent reassurance during the process; and clarification of the information provided. Survey results showed that concerns about fetal remains, emotional well-being, and the risk of an incomplete abortion (retained tissue) were strongly associated with women's sense of being informed. Emotional responses also shaped these perceptions, where women who felt stressed were less likely to feel adequately informed, while those women who felt happy were more likely to report receiving sufficient information. Integration of qualitative and quantitative findings revealed consistent concerns, particularly about unanticipated symptoms, emotional distress, and the need for clearer guidance. Our results suggest that some women experience uncertainty or unmet informational needs prior to taking abortion medications, regardless of care setting. This informational gap raises the possibility of preference misalignment, whereby patients' expectations may not fully reflect their lived experience. The findings highlight a pressing need for clearer, more comprehensive, and emotionally supportive consent practices, particularly as medication abortion becomes increasingly accessible and utilized by women. Addressing these gaps can strengthen patient-centered care and ensure that women's choices are informed, respected, and aligned with their values.
Previous studies suggest endogenous ovarian hormones significantly increase binge-eating (BE) risk in females. Approximately 85% of women use combined oral contraceptives (COCs) that mimic the riskiest hormonal milieu for BE (ie, elevated estradiol and progesterone postovulation). The effects of COCs on BE risk remain unknown. To examine the associations of COCs with BE. This population-based longitudinal survey study collected daily reports of COC active vs inactive pill use and BE across 49 consecutive days in women from the Michigan State University Twin Registry. Analyses examined within-person changes in a continuous measure of BE (ie, emotional eating [EE]) when women were using active hormone pills vs inactive pills. Data were collected from 2017 to 2024. Participants were women already using monophasic COCs. Analyses examined the full sample as well as women with clinically defined BE episodes. Data were analyzed from April 2024 to November 2025. COC pill type (active vs inactive pills). The outcome of interest was within-person changes in EE between inactive vs active hormone pills, controlling for negative affect. Changes across 2 pill packs were examined for replication. Analyses also examined weight preoccupation (WP) as a control outcome, given its lack of past associations with ovarian hormones. Primary models focused on the full sample; sensitivity analyses examined women with clinically defined BE. A total of 422 women (mean [SD] age, 21.95 [3.10] years) were included in the full sample. Significant within-person increases in EE were observed in the full sample during active hormone vs inactive pills in both cycles (cycle 1: β = 0.11 [95% CI, 0.06 to 0.16]; cycle 2: β = 0.07 [95% CI, 0.04 to 0.10]). Increases were not mediated by changes in negative affect and were observed in the subsample of 51 women (mean [SD] age, 22.44 [3.57] years) with clinically defined BE episodes (cycle 1: β = 0.13 [95% CI, -0.07 to 0.33]; cycle 2: β = 0.12 [95% CI, 0.02 to 0.23]. Importantly, no significant changes in WP were observed across pill type, and post hoc analyses of negative affect as the outcome showed more modest COC outcomes. This intensive, daily survey study of COC use found a specific association of active COC pills with risk for EE. Future studies are needed to identify for whom COCs are most risky to inform personalized medicine and identify contraceptive options that may be less likely to impact BE or EE.
Differences in typical-use contraceptive failure rates between long-acting reversible contraception (LARC; such as intrauterine devices [IUDs] and implants) and shorter-acting methods (depot medroxyprogesterone acetate [DMPA], pills, rings, and male condoms) are often the focus of contraceptive counseling, but assessments of contraceptive counseling have not focused on contraceptive effectiveness over time. To assess 3-year continuation and typical-use contraceptive failure rates for 7 reversible contraceptive methods provided with access barriers removed. The HER Salt Lake Contraceptive Initiative was a 3-year prospective longitudinal cohort study (September 2015 to March 2017, with follow-up data collected through June 2020). Participants (new contraceptive users 18-45 years who indicated they wanted to avoid pregnancy for at least 1 year) enrolled at 4 family planning clinics in Salt Lake County, Utah, and received person-centered contraception counseling and same-day access to the reversible contraceptive method of their choice. Data were analyzed from June 2024 to February 2026. The exposure was contraceptive method selected at baseline (copper IUD, DMPA, implant hormonal IUD, condoms, pill, or ring). The outcome was experiencing a contraceptive failure, defined as an unintended pregnancy (self-reported or identified through electronic medical record) experienced while using a contraceptive method in the previous 4 weeks. Method-specific continuation and failure rates were calculated using a life table analysis. Among 4275 contraceptive users (1759 [41%] aged 20-24 years), 96 pregnancies resulting from contraceptive failures of methods initiated at baseline were identified. Of all participants, 529 (11%) selected a copper IUD, 558 (13%) selected DMPA, 823 selected an implant (19%), 1025 (24%) selected a hormonal IUD, 52 (<1%) selected condoms, 1065 (25%) selected pills, and 223 (5%) selected the ring. Cumulative continuation at 3 years included 741 hormonal IUD users (72%), 455 implant users (55%), 321 copper IUD users (61%), 186 DMPA users (33%), 75 ring users (34%), 376 pill users (35%), and 8 male condom (15%). Three-year contraceptive failure rates per 100 person-years were 0.7 (95% CI, 0.4-1.1) for hormonal IUD users, 0.8 (95% CI, 0.5-1.3) for implant users, 1.1 (95% CI, 0.6-1.8) for copper IUD users, 1.1 (95% CI, 0.6-2.1) for DMPA users, 1.4 (95% CI, 0.6-3.2) for ring users, 1.6 (95% CI, 1.1-2.3) for pill users, and 2.6 (95% CI, 0.5-10.0) for male condom users. In this cohort study of individuals initiating a contraceptive method following person-centered contraceptive counseling and removal of access barriers, low 3-year contraceptive failure rates were observed for all methods, and shorter-acting methods had lower failure rates than previously reported typical use rates. These findings suggest that removing access barriers to preferred contraceptive methods may support access to clinician-dependent LARC methods, like IUDs and implants, and improve the contraceptive effectiveness of user-controlled, shorter-acting methods.
Background/Objectives: Intra-articular hyaluronic acid (HA) injections are widely used to treat pain and functional limitations in knee osteoarthritis (KOA). However, evidence on their real-world effectiveness in routine clinical practice and their impact on analgesic medication use remains limited. This study assessed changes in analgesic prescribing following HA injections in a large real-world outpatient population. Methods: This retrospective cohort study used data from the IQVIA™ Disease Analyzer database in Germany. Patients with knee osteoarthritis who received a first 20 mg hyaluronic acid injection between 2011 and 2024 and had at least three months of observation before and after treatment were included. Outcomes were (1) the proportion of patients with any analgesic prescription (EPHMRA ATC codes M01A, N02A, N02B) and (2) changes in the number of prescribed analgesic pills within three months before versus after injection. Multivariable logistic regression models evaluated factors associated with post-treatment analgesic prescriptions and reductions in pill counts. Results: A total of 4696 patients were included (mean age 64.5 years; 53.9% women), including 524 treated with Recosyn and 4172 treated with other HA products. The proportion of patients with analgesic prescriptions decreased from 28.6% before injection to 26.2% after injection (p = 0.004). Among Recosyn-treated patients, the proportion declined from 25.0% to 20.0% (p = 0.028). Overall, 70.8% of patients with baseline analgesic use achieved a ≥10% reduction in pill counts and 70.0% achieved a ≥20% reduction. In multivariable analyses, treatment with Recosyn was associated with lower odds of receiving an analgesic prescription after injection (OR 0.67; 95% CI 0.53-0.85) and higher odds of achieving a ≥10% reduction in analgesic pill count (OR 1.64; 95% CI 1.05-2.58). Conclusions: In routine outpatient practice, HA injections were accompanied by modest reductions in analgesic prescribing among patients with KOA. Numerically greater reductions were observed among patients treated with Recosyn compared with other HA products; however, these findings should be interpreted with caution given the observational design, potential residual confounding, and the absence of a non-treated comparator group. These results should be considered hypothesis-generating.
Contraceptive discontinuation rates in Indonesia are higher among short-acting contraceptive users. The quality of family planning services was suspected to be the cause. The Indonesian Demographic Health Survey (IDHS) assesses family planning, discontinuation rates, and factors related to family planning. This study aimed to analyze short-acting contraceptive discontinuation and the quality of family planning services using The IDHS 2017 data. This research analyzes data from the 2017 IDHS of women aged 15-49 years who had been using contraception in the last five years preceding the survey. Data on contraceptive discontinuation rates, reasons for discontinuation, contraceptive methods, sources of family planning services, caregivers, contraceptive decision makers, and contraceptive payment methods were extracted from the survey. Family planning service quality was assessed through the method information index (MII) from the 2017 IDHS. Survival analysis and the Cox proportional hazard model were used to analyze family planning service quality and contraceptive discontinuation. The overall contraceptive discontinuation rate for short-acting contraceptive method (pills, injectable) in Indonesia was 43.6%. The complete MII or informed choice rate was 30%. Episodes with complete MII discontinue earlier than those incomplete. Approximately 60% of the discontinuations involved the use of injectables, but pill users discontinued earlier. The main reason for discontinuation is side effects. The Cox proportional hazard model revealed several variables that were significantly associated: complete MII (Hazard Ratio or HR 1.1), the use of a pill (HR 2.9) or an injectable contraceptive (HR 2.8), switching to other methods (HR 7.5), switching to long-acting reversible contraception (LARC) (HR 6,9), the use of other service sources (HR 2.0), age ≤ 29 years (HR 1.4), and age 30-34 years (HR 1.2). The number of contraceptive discontinuation episodes in Indonesia was quite high, with few informed choices, although those with informed choices discontinued earlier. It is possible that those with informed choice acknowledge the contraceptive side effects and then choose to discontinue. Considering those who discontinue and switch to other methods, it is crucial to improve the quality of counseling with the aim of making optimal informed choices.
Hypertension remains a leading contributor to global cardiovascular (CV) morbidity and mortality, yet blood pressure (BP) control rates remain suboptimal worldwide. Therapeutic inertia, delayed treatment intensification, dose-dependent adverse effects, and limited healthcare access continue to hinder effective management. Low-dose combination therapy has emerged as a strategy to enhance efficacy while improving tolerability by targeting complementary pathophysiological pathways at reduced drug doses. This review describes the evolution of low- and ultra-low-dose combination therapy from its pharmacologic rationale and early proof-of-concept studies to contemporary randomized and pragmatic trials. Meta-analytic and clinical evidence have demonstrated that combining antihypertensive agents at fractional doses produces additive BP reductions with fewer dose-related adverse effects. Subsequent trials evaluating quarter-dose and one-third-dose multidrug regimens confirmed substantial BP lowering with favorable safety profiles. Pragmatic studies further supported the feasibility of simplified, protocol-based single-pill strategies in real-world and resource-limited settings. More recent phase III trials have shown that single-pill low- and ultra-low-dose triple combinations achieve BP reductions comparable to or greater than those of standard-dose monotherapy, without compromising safety. Current evidences support low- and ultra-low-dose single-pill combination therapy as a practical and scalable first-line approach to improving global hypertension control. However, the current evidence base is dominated by trials evaluating short-term BP lowering rather than long-term CV outcomes. Although the magnitude and consistency of BP reduction provide a strong rationale for this strategy, evidence for reductions in CV events and mortality is warranted.
Background/Objectives: Fixed orthodontic appliances interfere with oral hygiene and contribute to plaque retention, gingival inflammation and demineralization of enamel. Standard techniques for keeping oral hygiene (tooth brushing, mouthwashes, dental floss, interdental brush, etc.) are not sufficiently effective. The aim of this study was to investigate the effectiveness, safety, tolerability, and influence on quality of life of an electrolysis device being added to standard techniques of oral hygiene in orthodontic patients, compared to standard methods only. Methods: This 6-month study was designed as an observational prospective-cohort investigation. Primary outcomes of the study were indices of gingival inflammation and bleeding, dental plaque indices, the number of white spots on enamel, and safety (incidence of adverse events). Secondary outcomes were quality of life and overall costs of keeping oral hygiene. Results: The addition of the Neo Pill device to standard oral hygiene maintenance measures was associated with improvements in oral health indices after 6 months; however, given the non-randomized, preference-driven design, these findings reflect an association and should not be interpreted as evidence of causal efficacy. After 6 months, the primary outcomes of the study were significantly reduced compared to the application of only standard oral hygiene methods (from 21 to 55% reduction); the quality of life related to oral health was higher (for 14%), the tolerability of maintaining oral hygiene was the same as with standard measures and the costs of maintaining oral hygiene consumables were lower in the Neo Pill group (median difference 30%); however, this figure excludes the acquisition cost of the device itself, which was donated to all participants by the manufacturer, and the 95% confidence interval for this difference includes zero. Conclusions: The addition of an electrolysis device to standard oral hygiene maintenance measures in people wearing fixed orthodontic appliances was associated with improvements in gingival inflammation, papillary bleeding, and dental plaque indices-outcomes measured with established clinical instruments. Apparent reductions in white-spot lesion counts were also observed but should be considered exploratory given the absence of calibrated or blinded lesion assessment. These findings are preliminary and do not establish causal efficacy.
Home telemonitoring programs are increasingly used to support older adults living with chronic conditions such as heart failure (HF). While these interventions show promise for improving health outcomes and reducing care burden, their effectiveness depends largely on how patients and caregivers integrate digital technologies into everyday life and care relationships. However, relatively few studies have examined these experiences using conceptual frameworks that capture both functional and relational dimensions of care. This study aimed to explore the experiences of older adults and their informal caregivers participating in a home telemonitoring program for HF. Drawing on the Person-Based Approach and the Person-Centered Practice frameworks, we examined how participants engaged with both the technofunctional and relational aspects of the intervention. We conducted a qualitative study involving 34 patients, 28 informal caregivers, and 20 nurses across 3 primary care organizations in Quebec, Canada. The 6-month intervention included 4 connected devices used by patients (smartwatch, Bluetooth-enabled scale, voice-activated tablet, and a smart pill dispenser [xPill; Domedic]) and a mobile app for caregivers, complemented by remote nursing follow-up. Nurses reviewed patient data through a clinical dashboard at least once daily during weekday daytime shifts. Data were collected through semistructured interviews and field notes and analyzed using directed content analysis. Participants' experiences revealed both enabling and constraining factors across 2 key dimensions. Technofunctional engagement was shaped by digital literacy, emotional responses to the technology, alignment with daily routines, and access to technical or caregiver support. Relational aspects of care were influenced by perceived professional presence, opportunities for communication and shared decision-making, and the degree of emotional reassurance provided by remote monitoring. While many participants reported increased confidence and a sense of being supported, others experienced frustration, fatigue, or disengagement when the system disrupted routines or when feedback from clinicians was perceived as limited. Engagement with home telemonitoring technologies among older adults depends not only on usability but also on the relational context in which these technologies are embedded. Combining technofunctional and relational perspectives provides a more comprehensive understanding of how telemonitoring interventions are experienced and highlights the importance of personalized support, reliable technology, and sustained clinical engagement to promote meaningful adoption.
There are widespread changes occurring in contraceptive use, with people moving away from oral contraceptive pills and toward intrauterine devices. Considerable data support the risk reduction for ovarian cancer with oral contraceptive use, but there is little evidence on how levonorgestrel intrauterine device use affects ovarian cancer risk. This paper examines ovarian cancer risk in levonorgestrel intrauterine device users in British Columbia, Canada, between 2002 and 2021. This research used population-based data from British Columbia to analyze the risk of ovarian cancer in levonorgestrel intrauterine device users, compared with never users, while controlling for previous oral contraceptive use and age. The final cohort included 788,736 individuals, of whom 52,888 were exposed to the levonorgestrel intrauterine device. Exposed individuals were younger on average and were more likely to have used oral contraceptives. During follow-up, ovarian cancer was diagnosed in 17 exposed individuals and 1184 unexposed individuals. After adjustment for age and oral contraceptive use, levonorgestrel intrauterine device exposure was associated with a reduced risk of ovarian cancer (adjusted hazard ratio 0.57, 95% confidence interval 0.35 to 0.93). In an age-matched 1:1 cohort (n = 105,776), the association was similar but less precise (adjusted hazard ratio 0.61, 95% confidence interval 0.24 to 1.12). In a subgroup restricted to individuals older than 60 years by the end of follow-up (n = 211,866), based on 8 exposed and 720 unexposed ovarian cancer cases, levonorgestrel intrauterine device exposure was not associated with reduced ovarian cancer risk (adjusted hazard ratio 1.59, 95% confidence interval 0.79 to 3.21). While the findings from the main cohort suggest that use of the levonorgestrel intrauterine device reduced the risk of ovarian cancer, this effect appeared to be confounded by age. These results should be interpreted with caution, as many levonorgestrel intrauterine device users are young and have not reached an age at which they are at a significant risk of ovarian cancer.