Auricular Acupuncture Prior to Menstruation Can Reduce Primary Dysmenorrhea: A Randomized Controlled Trial.

Objective: Primary dysmenorrhea is a common condition that impacts quality of life significantly. Auricular therapies have shown promise for treating primary dysmenorrhea, but there is a lack of evidence specifically for auricular acupuncture (AA). This study evaluated the safety and efficacy of AA for managing primary dysmenorrhea. Materials and Methods: A randomized, double-blinded controlled trial was conducted on 90 females with primary dysmenorrhea: an AA group; n = 45) and a sham-AA (SA) group; n = 45. Specific ear acupoints (i.e., Uterus, Endocrine, Shenmen, Subcortex, Liver, and Kidney) were used for the intervention, which was 1 or 2 days prior to the expected menstruation onset. Outcomes were visual analogue scale (VAS) scores, ibuprofen needs, and adverse events (AEs). Results: The AA group had significantly lower VAS scores, compared to the SA group at menstruation onset and for up to 12 hours (mean differences [MDs] and 95% confidence intervals [CIs]: -1.08 [-1.96, -0.21] and -1.17 [-2.16, -0.18], respectively). Both groups had reductions in pain levels, compared to the prior menstrual cycle; the AA group had a significantly greater improvement. The AA group needed fewer ibuprofen tablets (MD: -0.28; 95% CI: -0.58, 0.00]). AEs were mild pain and irritation at insertion sites, all resolved spontaneously with no lasting effects. Conclusions: AA is safe. It may be effective for managing primary dysmenorrhea. Further studies are warranted on AA's effectiveness in diverse populations and extended times.

Thread-embedding acupuncture may improve symptom resolution in patients with gastroesophageal reflux disease: A randomized controlled trial.

Background: Various traditional medicine treatments have been investigated to treat GERD. Among those, thread-embedding acupuncture (TEA) has the advantage that patients need to undergo the procedure infrequently; however, its efficacy is unclear. This study evaluated the efficacy of TEA in treating GERD. Methods: A randomized controlled trial was conducted with 66 participants with GERD: 33 received two sessions of TEA + standard therapy (proton-pump inhibitor [PPI]) (TEA+PPI group) and 33 received PPI alone (PPI group). Primary outcomes included GerdQ score and heartburn and regurgitation resolution. Secondary outcomes were antacids requirement, the Frequency Scale for Symptoms of GERD (FSSG) score, and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) score. The safety outcome was adverse events (AEs). Results: After four weeks of treatment, the TEA+PPI group significantly reduced the GerdQ score (mean difference [MD] and 95% confidence interval [CI]: -1.8 [-2.4, -1.1]) and increased the rate of heartburn and regurgitation resolution compared to PPI (54.5% versus 9.1%, respectively) compared to PPI. The TEA+PPI group also significantly reduced the number of antacid packs used (MD [95%-CI]: -9.4 [-12.1, -6.7]), FSSG score (MD [95%-CI]: -9.4 [-11.0, -7.8]), and GERD-HRQL score (MD [95%-CI]: -5.6 [-7.7, -3.5]) compared to PPI. Five patients experienced AEs, which were mild local complications at the acupoints. Conclusion: TEA combined with PPI is more effective than PPI alone in treating GERD. Further studies with longer follow-ups are required to confirm these findings. Clinical trials registration information: ClinicalTrials.gov, NCT05353933.

Impact of multimorbidity and complex multimorbidity on mortality among older Australians aged 45 years and over: a large population-based record linkage study.

OBJECTIVES: Multimorbidity (MM, co-occurrence of two or more chronic conditions) and complex multimorbidity (CMM, three or more chronic conditions affecting three or more different body systems) are used in the assessment of complex healthcare needs and their impact on health outcomes. However, little is known about the impacts of MM and CMM on mortality in Australia. DESIGN: Community-based prospective cohort study. SETTING: New South Wales, Australia. PARTICIPANTS: People aged 45 years and over who completed the baseline survey of the 45 and Up Study. MEASURES: Baseline survey data from the 45 and Up Study were linked with deaths registry data. Deaths that occurred within 8 years from the baseline survey date were the study outcome. Eleven self-reported chronic conditions (cancer, heart disease, diabetes, stroke, Parkinson's disease, depression/anxiety, asthma, allergic rhinitis, hypertension, thrombosis and musculoskeletal conditions) from the baseline survey were included in the MM and CMM classifications. Cox proportional hazard models were used to estimate adjusted and unadjusted 8-year mortality hazard ratios (HRs). RESULTS: Of 251 689 people (53% female and 54% aged ≥60 years) in the cohort, 111 084 (44.1%) were classified as having MM and 39 478 (15.7%) as having CMM. During the 8-year follow-up, there were 25 891 deaths. Cancer (34.7%) was the most prevalent chronic condition and the cardiovascular system (50.9%) was the body system most affected by a chronic condition. MM and CMM were associated with a 37% (adjusted HR 1.36, 95% CI 1.32 to 1.40) and a 22% (adjusted HR 1.22, 95% CI 1.18 to 1.25) increased risk of death, respectively. The relative impact of MM and CMM on mortality decreased as age increased. CONCLUSION: MM and CMM were common in older Australian adults; and MM was a better predictor of all-cause mortality risk than CMM. Higher mortality risk in those aged 45-59 years indicates tailored, person-centred integrated care interventions and better access to holistic healthcare are needed for this age group.

Protective effect of kava constituents in an in vitro model of oral mucositis.

PURPOSE: Oral mucositis is a debilitating inflammatory disorder observed in patients undergoing active cancer treatment, particularly cancer of the head and neck region. A key pathway believed to be involved in the pathogenesis of oral mucositis is the formation of reactive oxygen species (ROS). The identification of compounds that can inhibit this pathway may therefore be of benefit in treating this disorder. The kava plant (Piper methysticum) contains various constituents, including flavokawain A (FKA), flavokawain B (FKB), yangonin, methysticin and kavain. These constituents are known to be biologically active and possess anti-oxidative properties. This study therefore focused on examining these constituents for their effect on ROS formation in an in vitro oral mucositis model. METHODS: Cell proliferation was assessed in normal oral keratinocytes (OKF6) treated with and without kava constituents, namely FKA, FKB, yangonin, methysticin and kavain using an MTS in vitro assay. Oxidative stress was assessed by co-treating and pre-treating OKF6 cells with H2O2. The effects were quantified by analysis of ROS production, using a CM-H2DCFDA assay. RESULTS: Pre-treatment of cells for 24 h with 2.5 µg/ml kavain and 5 µg/ml FKA demonstrated a significant protective anti-oxidative effect. Similarly, FKB at a concentration of 2.5 µg/ml, demonstrated a trend of ROS reduction but was observed to be cytotoxic at concentrations greater than 5 µg/ml. Reduction in ROS production by methysticin and yangonin was compromised by their cell cytotoxicity. CONCLUSION: This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis.

Maternal choline supplementation ameliorates Alzheimer's disease pathology by reducing brain homocysteine levels across multiple generations.

The lack of effective treatments for Alzheimer's disease (AD) is alarming, considering the number of people currently affected by this disorder and the projected increase over the next few decades. Elevated homocysteine (Hcy) levels double the risk of developing AD. Choline, a primary dietary source of methyl groups, converts Hcy to methionine and reduces age-dependent cognitive decline. Here, we tested the transgenerational benefits of maternal choline supplementation (ChS; 5.0 g/kg choline chloride) in two generations (Gen) of APP/PS1 mice. We first exposed 2.5-month-old mice to the ChS diet and allowed them to breed with each other to generate Gen-1 mice. Gen-1 mice were exposed to the ChS diet only during gestation and lactation; once weaned at postnatal day 21, Gen-1 mice were then kept on the control diet for the remainder of their life. We also bred a subset of Gen-1 mice to each other and obtained Gen-2 mice; these mice were never exposed to ChS. We found that ChS reduced Aß load and microglia activation, and improved cognitive deficits in old Gen-1 and Gen-2 APP/PS1 mice. Mechanistically, these changes were linked to a reduction in brain Hcy levels in both generations. Further, RNA-Seq data from APP/PS1 hippocampal tissue revealed that ChS significantly changed the expression of 27 genes. These genes were enriched for inflammation, histone modifications, and neuronal death functional classes. Our results are the first to demonstrate a transgenerational benefit of ChS and suggest that modifying the maternal diet with additional choline reduces AD pathology across multiple generations.

Surveillance colonoscopy in elderly patients: a retrospective cohort study.

IMPORTANCE: The risks and benefits of surveillance colonoscopy in elderly patients have not been well characterized. OBJECTIVE: To investigate the relative impact of surveillance colonoscopy in elderly patients compared with a reference cohort. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study from 2001 through 2010 of patients 50 years and older undergoing surveillance colonoscopy for a history of colorectal cancer (CRC) or adenomatous polyps at an integrated health care system in southern California. Patients were followed up from the surveillance examination until CRC diagnosis, death, disenrollment, IBD diagnosis, or study end date (December 31, 2010). MAIN OUTCOMES AND MEASURES: The primary outcome measure was incidence of CRC detected following surveillance colonoscopy. The secondary outcome was risk of procedure defined as postprocedure hospitalization within 30 days. Cox regression and multivariable logistic regression analyses were used to determine the impact of age on CRC incidence on surveillance examination as well as postprocedure hospitalization, respectively. RESULTS: The study cohort included 4834 elderly patients (age ≥75 years; 55.8% male) (median surveillance age, 79 years) and 22 929 individuals in the reference group (age 50-74 years; 57.7% male) (median surveillance age, 63 years). A total of 373 cancers were detected following surveillance colonoscopy (368 in the reference group and 5 among the elderly patients). There were a total of 711 postprocedure hospitalizations (184 in the reference group and 527 among the elderly patients). The CRC incidence among elderly patients undergoing surveillance was 0.24 per 1000 person-years vs 3.61 per 1000 person-years in the reference population (P < .001). In Cox regression analysis, the hazard ratio for CRC in the elderly patients compared with the reference group was 0.06 (95% CI, 0.02-0.13) (P < .001) after adjusting for comorbid illness, sex, and race/ethnicity. In logistic regression analysis, age 75 years and older was independently associated with increased risk of postprocedure hospitalization (adjusted odds ratio, 1.28 [95% CI, 1.07-1.53]; P = .006). Charlson score of 2 was also independently associated with increased risk of postprocedure hospitalization (adjusted odds ratio, 2.54 [95% CI, 2.06-3.14]; P < .001). CONCLUSIONS AND RELEVANCE: A low incidence of CRC and relatively high rate of postprocedure hospitalization were found among elderly patients undergoing surveillance colonoscopy. Recommendations for ongoing surveillance in the elderly population should take into consideration the impact of comorbid illness and increasing age on the anticipated risks and benefits of colonoscopy.

Calcium carbonate does not affect nilotinib pharmacokinetics in healthy volunteers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Gastric upset is a common side effect of nilotinib therapy, and calcium carbonate is frequently used concomitantly, either as antacid or as calcium supplementation. With the increasing number of oral agents in cancer therapy, oral drug-drug interactions are becoming more relevant. Nilotinib has already been shown to be absorbed to a much lesser extent when co-administered with proton pump inhibitors. Because exposure to sub-therapeutic concentrations of anticancer drugs such as nilotinib may result in selection of resistant clones and ultimately relapse, we studied the effect of a calcium carbonate supplement (Tums Ultra 1000®) on nilotinib pharmacokinetics. WHAT THIS STUDY ADDS: Calcium carbonate may be co-administered with nilotinib without significantly affecting the pharmacokinetics of nilotinib and potentially impacting efficacy. PURPOSE: Nilotinib is a second-generation oral tyrosine kinase inhibitor with superior efficacy compared with imatinib mesylate in the treatment for chronic phase chronic myelogenous leukemia. Calcium carbonate is commonly used as a source of calcium supplementation or as antacid to ameliorate the gastrointestinal side effects associated with nilotinib, which could have unknown effects on nilotinib absorption. The purpose of this study was to provide information on the effect of calcium carbonate on the PK of nilotinib in healthy volunteers. METHODS: Healthy subjects were enrolled in a two-period, open-label, single-institution, randomized, cross-over, fixed-schedule study. In one period, each subject received 400 mg of nilotinib p.o. In the other period, 4,000 mg of calcium carbonate (4 X Tums Ultra 1000®) was administered p.o. 15 min prior to the nilotinib dose. Plasma samples were collected at specified timepoints, concentrations of nilotinib were quantitated by LC-MS, and data were analyzed non-compartmentally. RESULTS: Eleven subjects were evaluable. Calcium supplementation did not significantly affect nilotinib pharmacokinetic parameters including area under the plasma concentration versus time curve (18.4 µg/mL h alone vs. 16.9 µg/mL h with calcium carbonate, p = 0.83; 80 % power); maximum plasma concentration (C(max)) (0.670 µg/mL alone vs. 6.18 µg/mL with calcium carbonate, p = 0.97); or half-life (18.9 h alone vs. 17.2 h with calcium carbonate, p = 0.18). CONCLUSIONS: Our results indicate that the use of calcium carbonate does not significantly affect nilotinib pharmacokinetics.