The Role of Insomnia and Exercise in COVID-19 Worries for Psychological Distress in Hong Kong Chinese: A Moderated Mediation Model.

OBJECTIVE: To examine the role of insomnia as a mediator between worrying and mental health and whether the association between worrying and insomnia is moderated by the levels of exercise frequency. METHODS: A cross-sectional online survey was conducted during the fourth wave of the COVID-19 outbreak in Hong Kong (n = 988). Participants' insomnia, psychological distress, and exercise frequency were evaluated. A mediation analysis was performed to examine the direct effect of COVID-19 worries and their indirect effect through insomnia on psychological distress. RESULTS: A significant indirect effect of COVID-19 worries through insomnia was found on psychological distress (beta = 0.18, SE = 0.02, 95% CI = 0.14-0.22, p < .001). The significant index of moderated mediation supported the moderating effect of exercise frequency on the indirect effect of COVID-19 worries on psychological distress (IMM = 0.06, SE = 0.02, 95% CI = 0.02-0.10, p = .006). The conditional indirect effects of insomnia on psychological distress were significant in individuals with mean and higher exercise frequency but not in those with lower exercise frequency. CONCLUSION: COVID-19 worries increased psychological distress through the worsening of sleep, and such an array of COVID-19 worries on insomnia was moderated by exercise frequency. Engaging more frequent exercise could reduce insomnia in people with less COVID-19 worries.

MK-8719, a Novel and Selective O-GlcNAcase Inhibitor That Reduces the Formation of Pathological Tau and Ameliorates Neurodegeneration in a Mouse Model of Tauopathy.

Deposition of hyperphosphorylated and aggregated tau protein in the central nervous system is characteristic of Alzheimer disease and other tauopathies. Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification, and O-GlcNAcylation of tau has been shown to influence tau phosphorylation and aggregation. Inhibition of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc moieties, is a novel strategy to attenuate the formation of pathologic tau. Here we described the in vitro and in vivo pharmacological properties of a novel and selective OGA inhibitor, MK-8719. In vitro, this compound is a potent inhibitor of the human OGA enzyme with comparable activity against the corresponding enzymes from mouse, rat, and dog. In vivo, oral administration of MK-8719 elevates brain and peripheral blood mononuclear cell O-GlcNAc levels in a dose-dependent manner. In addition, positron emission tomography imaging studies demonstrate robust target engagement of MK-8719 in the brains of rats and rTg4510 mice. In the rTg4510 mouse model of human tauopathy, MK-8719 significantly increases brain O-GlcNAc levels and reduces pathologic tau. The reduction in tau pathology in rTg4510 mice is accompanied by attenuation of brain atrophy, including reduction of forebrain volume loss as revealed by volumetric magnetic resonance imaging analysis. These findings suggest that OGA inhibition may reduce tau pathology in tauopathies. However, since hundreds of O-GlcNAcylated proteins may be influenced by OGA inhibition, it will be critical to understand the physiologic and toxicological consequences of chronic O-GlcNAc elevation in vivo. SIGNIFICANCE STATEMENT: MK-8719 is a novel, selective, and potent O-linked N-acetylglucosamine (O-GlcNAc)-ase (OGA) inhibitor that inhibits OGA enzyme activity across multiple species with comparable in vitro potency. In vivo, MK-8719 elevates brain O-GlcNAc levels, reduces pathological tau, and ameliorates brain atrophy in the rTg4510 mouse model of tauopathy. These findings indicate that OGA inhibition may be a promising therapeutic strategy for the treatment of Alzheimer disease and other tauopathies.

Identifying High-Risk Individuals for Chronic Kidney Disease: Results of the CHERISH Community Demonstration Project.

BACKGROUND: Most people with chronic kidney disease (CKD) are not aware of their condition. OBJECTIVES: To assess screening criteria in identifying a population with or at high risk for CKD and to determine their level of control of CKD risk factors. METHOD: CKD Health Evaluation Risk Information Sharing (CHERISH), a demonstration project of the Centers for Disease Control and Prevention, hosted screenings at 2 community locations in each of 4 states. People with diabetes, hypertension, or aged ≥50 years were eligible to participate. In addition to CKD, screening included testing and measures of hemoglobin A1C, blood pressure, and lipids. -Results: In this targeted population, among 894 people screened, CKD prevalence was 34%. Of participants with diabetes, 61% had A1C < 7%; of those with hypertension, 23% had blood pressure < 130/80 mm Hg; and of those with high cholesterol, 22% had low-density lipoprotein < 100 mg/dL. CONCLUSIONS: Using targeted selection criteria and simple clinical measures, CHERISH successfully identified a population with a high CKD prevalence and with poor control of CKD risk factors. CHERISH may prove helpful to state and local programs in implementing CKD detection programs in their communities.

ESRD due to Multiple Myeloma in the United States, 2001-2010.

Although management of multiple myeloma has changed substantially in the last decade, it is unknown whether the burden of ESRD due to multiple myeloma has changed, or whether survival of patients with multiple myeloma on RRT has improved. Regarding ESRD due to multiple myeloma necessitating RRT in the United States, we evaluated temporal trends between 2001 and 2010 for demography-adjusted incidence ratios, relative to rates in 2001-2002, and mortality hazards from RRT initiation, relative to hazards in 2001-2002. In this retrospective cohort study, we used the US Renal Data System database (n=1,069,343), 2001-2010, to identify patients with ESRD due to multiple myeloma treated with RRT (n=12,703). Demography-adjusted incidence ratios of ESRD from multiple myeloma decreased between 2001-2002 and 2009-2010 in the overall population (demography-adjusted incidence ratio 0.82; 95% confidence interval, 0.79 to 0.86) and in most demographic subgroups examined. Mortality rates were 86.7, 41.4, and 34.4 per 100 person-years in the first 3 years of RRT, respectively, compared with 32.3, 20.6, and 21.3 in matched controls without multiple myeloma. Unadjusted mortality hazards ratios declined monotonically after 2004 to a value of 0.72; 95% confidence interval, 0.67 to 0.77 in 2009-2010, and declines between 2001-2002 and 2008-2009 were observed (P<0.05) in most demographic subgroups examined. Findings were similar when adjustment was made for demographic characteristics, comorbidity markers, and laboratory test values. These data suggest the incidence of RRT from multiple myeloma in the United States has decreased in the last decade, and clinically meaningful increases in survival have occurred for these patients.

End-stage renal disease attributed to acute tubular necrosis in the United States, 2001-2010.

BACKGROUND/AIMS: Though end-stage renal disease (ESRD) is increasingly attributed to acute tubular necrosis (ATN), contemporary trends in the rates of incidence and recovery of renal function are poorly defined. Hence, we set out to describe the clinical epidemiology of ESRD due to ATN between 2001 and 2010. METHODS: We examined United States Renal Data System data (n = 1,070,490) for 2001 through 2010 to calculate the incidence rates and rates of renal recovery and death for patients with ESRD due to ATN treated with renal replacement therapy (RRT, n = 27,603). RESULTS: Standardized incidence ratios increased between 2001-2002 and 2009-2010 in the overall population (ratio 2.14), having risen in all demographic subgroups examined. Recovery of renal function was more likely in patients with ATN than in matched controls (cumulative incidence 23% vs. 2% at 12 weeks, 34% vs. 4% at 1 year), as was death (cumulative incidence 38% vs. 27% at 1 year). Hazards ratios for renal recovery increased stepwise with year of RRT inception to 1.34 (95% confidence interval 1.24-1.45) for 2009-2010 (vs. 2001-2002). In contrast, hazards ratios for death declined stepwise to 0.83 (0.79-0.87) in 2009-2010. CONCLUSION: While the incidence of ESRD attributed to ATN has increased, prospects of renal recovery and survival have also increased. Despite substantial mortality risk on RRT, renal recovery is not a rare occurrence.

Early mortality in patients starting dialysis appears to go unregistered.

Clinical experience suggests a heightened risk associated with the transition to maintenance dialysis but few national studies have systematically examined early mortality trajectories. Here we calculated weekly mortality rates in the first year of treatment for 498,566 adults initiating maintenance dialysis in the United States (2005-2009). Mortality rates were initially unexpectedly low, peaked at 37.0 per 100 person-years in week 6, and declined steadily to 14.8 by week 51. In both early (weeks 7-12) and later (weeks 13-51) time frames, multivariate mortality associations included older age, female, Caucasian, non-Hispanic ethnicity, end-stage renal disease (ESRD) from hypertension and acute tubular necrosis, ischemic heart disease, estimated glomerular filtration rate of 15 ml/min per 1.73 m(2) or more, shorter duration of nephrologist care, and hemodialysis, especially with a catheter. For early mortality risk, adjusted hazard ratios of 2 or more were seen with age over 65 (5.80 vs. under 40 years), hemodialysis with a catheter (2.73 vs. fistula), and age 40-64 (2.33). For later mortality risk, adjusted hazard ratios of 2 or more were seen with age over 65 (4.32 vs. under 40 years), hemodialysis with a catheter (2.10 vs. fistula), and age 40-64 (2.00). Thus, low initial mortality rates question the accuracy of data collected and are consistent with deaths occurring in the early weeks after starting dialysis not being registered with the United States Renal Data System.

Educational programs improve the preparation for dialysis and survival of patients with chronic kidney disease.

Preparation for end-stage renal disease (ESRD) is widely acknowledged to be suboptimal in the United States. We sought to determine whether participation in a kidney disease screening and education program resulted in improved ESRD preparation and survival in 595 adults who developed ESRD after participating in the National Kidney Foundation Kidney Early Evaluation Program (KEEP), a community-based screening and education program. Non-KEEP patients were selected from a national ESRD registry and matched to KEEP participants based on demographic and clinical characteristics. The main outcomes were pre-ESRD nephrologist care, placement of permanent vascular access, use of peritoneal dialysis, pre-emptive transplant wait listing, transplantation, and mortality after ESRD. Participation in KEEP was associated with significantly higher rates of pre-ESRD nephrologist care (76.0% vs. 69.3%), peritoneal dialysis (10.3% vs. 6.4%), pre-emptive transplant wait listing (24.2% vs. 17.1%), and transplantation (9.7% vs. 6.4%) but not with higher rates of permanent vascular access (23.4% vs. 20.1%). Participation in KEEP was associated with a lower risk for mortality (hazard ratio 0.80), but this was not statistically significant after adjusting for ESRD preparation. Thus, participation in a voluntary community kidney disease screening and education program was associated with higher rates of ESRD preparation and survival.

ESRD from autosomal dominant polycystic kidney disease in the United States, 2001-2010.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is amenable to early detection and specialty care. Thus, while important to patients with the condition, end-stage renal disease (ESRD) from ADPKD also may be an indicator of the overall state of nephrology care. STUDY DESIGN: Retrospective cohort study of temporal trends in ESRD from ADPKD and pre-renal replacement therapy (RRT) nephrologist care, 2001-2010 (n = 23,772). SETTING & PARTICIPANTS: US patients who initiated maintenance RRT from 2001 through 2010 (n = 1,069,343) from US Renal Data System data. PREDICTOR: ESRD from ADPKD versus from other causes for baseline characteristics and clinical outcomes; interval 2001-2005 versus 2006-2010 for comparisons of cohort of patients with ESRD from ADPKD. OUTCOMES: Death, wait-listing for kidney transplant, kidney transplantation. MEASUREMENTS: US census data were used as population denominators. Poisson distribution was used to compute incidence rates (IRs). Incidence ratios were standardized to rates in 2001-2002 for age, sex, and race/ethnicity. Patients with and without ADPKD were matched to compare clinical outcomes. Poisson regression was used to calculate IRs and adjusted HRs for clinical events after inception of RRT. RESULTS: General population incidence ratios in 2009-2010 were unchanged from 2001-2002 (incidence ratio, 1.02). Of patients with ADPKD, 48.1% received more than 12 months of nephrology care before RRT; preemptive transplantation was the initial RRT in 14.3% and fistula was the initial hemodialysis access in 35.8%. During 4.9 years of follow-up, patients with ADPKD were more likely to be listed for transplantation (IR, 11.7 [95% CI, 11.5-12.0] vs 8.4 [95% CI, 8.2-8.7] per 100 person-years) and to undergo transplantation (IR, 9.8 [95% CI, 9.5-10.0] vs 4.8 [95% CI, 4.7-5.0] per 100 person-years) and less likely to die (IR, 5.6 [95% CI, 5.4-5.7] vs 15.5 [95% CI, 15.3-15.8] per 100 person-years) than matched controls without ADPKD. LIMITATIONS: Retrospective nonexperimental registry-based study of associations; cause-and-effect relationships cannot be determined. CONCLUSIONS: Although outcomes on dialysis therapy are better for patients with ADPKD than for those without ADPKD, access to predialysis nephrology care and nondeclining ESRD rates may be a cause for concern.

Agreement of reported vascular access on the medical evidence report and on medicare claims at hemodialysis initiation.

BACKGROUND: The choice of vascular access type is an important aspect of care for incident hemodialysis patients. However, data from the Centers for Medicare & Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) identifying the first access for incident patients have not previously been validated. Medicare began requiring that vascular access type be reported on claims in July 2010. We aimed to determine the agreement between the reported vascular access at initiation from form CMS-2728 and from Medicare claims. METHODS: This retrospective study used a cohort of 9777 patients who initiated dialysis in the latter half of 2010 and were eligible for Medicare at the start of renal replacement therapy to compare the vascular access type reported on form CMS-2728 with the type reported on Medicare outpatient dialysis claims for the same patients. For each patient, the reported access from each data source was compiled; the percent agreement represented the percent of patients for whom the access was the same. Multivariate logistic analysis was performed to identify characteristics associated with the agreement of reported access. RESULTS: The two data sources agreed for 94% of patients, with a Kappa statistic of 0.83, indicating an excellent level of agreement. Further, we found no evidence to suggest that agreement was associated with the patient characteristics of age, sex, race, or primary cause of renal failure. CONCLUSION: These results suggest that vascular access data as reported on form CMS-2728 are valid and reliable for use in research studies.

Getting to Know the Effect Theory of Traditional Pediatric Tuina in the View of Modern Medicine in Three Minor Perspectives.

Pediatric tuina is a traditional Chinese medicine (TCM) modality that is well-accepted and applied in China currently. As a traditional medicine, it is based on TCM theories and clinical experience. In the TCM area, the "self-healing" system of the human body includes two aspects: self-regulation and adaptation, through which pediatric tuina could rectify dysfunctional states and guide the transition back to homeostasis. Pediatric tuina manipulations sufficiently, specifically, and accurately simulate certain sensory receptors in the skin, which in turn activates the internal self-healing function of the human body. We summarized the main opinions on pediatric tuina mechanism in ancient literature into three minor perspectives and demonstrated them by combining them with modern medical knowledge. First, children at a young age are more responsive to stimulations on the skin surface; second, the sensory receptors and pediatric tuina acupoints on the skin surface have a similar distribution pattern; third, the specific manipulations of pediatric tuina provide multiple stimuli that are detected by a variety of surface sensory receptors for information collection. Each point could be tested via clinical trials with appropriate-designed comparisons.

Views of Hong Kong Chinese medicine practitioners on the application of the "Chinese Medicine Anti-epidemic Plans" prepared by the Chinese medicine expert group of central authorities: a focus group study.

BACKGROUND: Drawing on the extensive utilization of traditional Chinese medicine (TCM) to combat COVID-19 in Mainland China, experts designed a series of TCM anti-epidemic strategies. This study aims to understand Hong Kong CM practitioners' application of and opinions on the "Chinese Medicine Anti-epidemic Plans." METHODS: Online focus group interviews were conducted, and purposive sampling was employed to invite 22 CM practitioners to voluntarily participate in three interview sessions. The interviews were audio recorded, then transcribed verbatim. The transcripts were analyzed using template analysis. RESULTS: Three themes were derived: (1) facilitators of the "Chinese Medicine Anti-epidemic Plans," (2) barriers of the "Chinese Medicine Anti-epidemic Plans," and (3) expectations on improving the "Chinese Medicine Anti-epidemic Plans." The participants could obtain relevant information from various sources, which highlights the value of the plans for TCM medicinal cuisine and non-pharmacologic therapies and guiding junior CM practitioners, supplementing Western medicine interventions, and managing Chinese herb reserves in clinics. However, the barriers included the lack of a specialized platform for timely information release, defective plan content, limited reference value to experienced CM practitioners, and lack of applicability to Hong Kong. The expectations of the CM practitioners for improving the plans were identified based on the barriers. CONCLUSIONS: To enhance the implementation of the anti-epidemic plans, CM practitioners in Hong Kong expect to utilize a specific CM platform and refine the plans to ensure that they are realistic, focused, comprehensive, and tailored to the local context.

Pediatric massage therapy in infants and children under 5 years: An umbrella review of systematic reviews.

Objective: To systematically evaluate and synthesize quantitative evidence regarding the effects of pediatric massage in infants and children under five years. Review methods: We conducted searches in databases including MEDLINE, Embase, Health Technology Assessment Database, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Allied and Complementary Medicine, Embase, the China National Knowledge Infrastructure, Wanfang Data, SinoMed, and CQVIP up to February 2024. Two reviewers independently screened articles, extracted data, and conducted quality appraisals on the included studies. We focused on systematic reviews with meta-analyses comparing pediatric tuina with a waitlist control, placebo, medication, massage combined with other interventions, and usual care. Outcomes analyzed included physical, psychological, developmental, and safety-related measures for children and their caregivers. Methodological quality was assessed using AMSTAR 2, and evidence quality was evaluated using the GRADE approach. Pooled effect estimates and heterogeneity were extracted for each meta-analyzed outcome. Evidence evaluated as 'high' and 'moderate' quality by GRADEpro with low heterogeneity are presented in the result section. Results: Twenty-two systematic reviews with meta-analysis of 81 outcomes were included. Seven studies (31.8 %) were high quality, and the evidence of 6 (7.4 %) outcomes were evaluated as high quality. The meta-analysis results demonstrate significant benefits of pediatric massage for infants compared to routine care, with increased weight gain (MD 455.07 g; 95 % CI 86.33 to 823.8; I2 = 0 %) based on 2 studies with 157 cases, length growth (MD 1.58 cm; 95 % CI 1.42 to 1.74; I2 = 25 %) from 9 studies with 1294 cases, reduced fussing (MD -0.37 time; 95 % CI -0.53 to -0.21; I2 = 30 %) according to 3 studies with 271 cases, and lower post-intervention bilirubin levels (3 studies/345 cases; MD -31.75 mmol/L; 95 % CI -40.05 to -23.46; I2 = 0 %). Pediatric massage was associated with reduced diarrhea incidence compared to waitlist controls (2 RCTs/310 cases; RR 0.39; 95 % CI 0.2 to 0.76; I2 = 0 %) and improved psychomotor development indices (4 RCTs/466 cases; SMD -0.35; 95 % CI -0.54 to -0.15; I2 = 1.06 %). Additionally, pediatric massage significantly enhanced blood oxygen saturation variation post-procedure for pain management (5 RCTs/355 cases; MD 1.05; 95 % CI 0.51 to 1.58; I2 = 0 %). Conclusions: Pediatric massage significantly enhances mother-child attachment, promotes physical growth, reduces fussing, lowers bilirubin levels, improves motor and psychomotor development, as well as manages digestive conditions and pain in children under 5 years. Future research should improve study quality and comprehensively report adverse events.

A longitudinal study on the change in sleep across three waves of the COVID-19 outbreaks in Hong Kong.

In the year 2020, Hong Kong experienced four COVID-19 epidemic waves. The present study aimed to examine the transition of sleep disturbances and explore its associated factors across the later three epidemic waves. Among the 1138 respondents who participated in an online survey at the second wave (T1, April 2020), 338 and 378 participants also completed a follow-up at the third (T2, August 2020) and fourth waves (T3, December 2020), respectively. Participants completed the Insomnia Severity Index and an investigator-designed questionnaire regarding potential factors associated with sleep change such as perceived risk of being infected, economic stress, and confidence in the government and health care professional. Sample of this study were mainly female (67.7%), married (50.3%), young adults (54.2%) with tertiary education (81.6%). Maintaining normal sleep was the most prevalent trajectory of sleep of all three waves (50.5%), followed by persistent insomnia (17.2%) and remitted insomnia (9.0%). Besides female, older-age and lower education level, the results showed that increment in worry about family being infected (adjusted risk ratio, RR = 1.28), perceived interference of daily lives (adjusted RR = 1.19), and economic distress (adjusted RR = 1.24) were significantly associated with the development of clinical insomnia during the three epidemic waves. These factors were also associated with worsening of other sleep parameters. Insomnia being persistent across the three waves of COVID-19 outbreaks was common. Increasing economic distress, daily interference, and worry about family members being infected were associated with an increasing risk of clinical insomnia across the three COVID-19 outbreaks. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00486-w.

Traditional Chinese medicine interventions based on meridian theory for pain relief in patients with primary dysmenorrhea: a systematic review and network meta-analysis.

Objective: To determine the comparative effects and safety of traditional Chinese medicine (TCM) interventions based on meridian theory for pain relief in patients with primary dysmenorrhea (PD). Methods: This is a systematic review with network meta-analysis. Randomized controlled trials (RCTs) comparing meridian-based TCM interventions with waitlist, placebo, western medicine, and conventional therapies for PD pain. A SUCRA was used to estimate the probability ranking for the effects of interventions. Results: 57 RCTs involving 3,903 participants and 15interventions were included. Thirty-two RCTs were rated as low risk of bias. A network diagram was drawn with 105 pairs of comparisons. Compared with NSAIDs and waitlist, significantly better effects were found in acupressure [SMD = -1.51, 95%CI (-2.91, -0.12)/SMD = -2.31, 95%CI (-4.61, -0.02)], warm needling [SMD = -1.43, 95%CI (-2.68, -0.18)/SMD = -2.23, 95%CI (-4.43, -0.03)], moxibustion [SMD = -1.21, 95%CI (-1.85, -0.57)/SMD = -2.10, 95%CI (-3.95, -0.07)], and acupuncture [SMD = -1.09, 95%CI (-1.62, -0.55)/SMD = -1.89, 95%CI (-3.67, -0.11)]. No adverse events were detected. Conclusion: For PD pain, the effects of acupressure, acupuncture, warm needling, and moxibustion were superior to those of NSAIDs and waitlist. Oral contraceptive pill, electro-acupuncture, acupressure, and warm needling demonstrated higher probabilities of being better interventions. More high-quality clinical trials are needed to provide more robust evidence of this network. Systematic review registration: PROSPERO CRD42022373312.

Non-contrasted computed tomography (NCCT) based chronic thromboembolic pulmonary hypertension (CTEPH) automatic diagnosis using cascaded network with multiple instance learning.

Objective.The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is challenging due to nonspecific early symptoms, complex diagnostic processes, and small lesion sizes. This study aims to develop an automatic diagnosis method for CTEPH using non-contrasted computed tomography (NCCT) scans, enabling automated diagnosis without precise lesion annotation.Approach.A novel cascade network (CN) with multiple instance learning (CNMIL) framework was developed to improve the diagnosis of CTEPH. This method uses a CN architecture combining two Resnet-18 CNN networks to progressively distinguish between normal and CTEPH cases. Multiple instance learning (MIL) is employed to treat each 3D CT case as a 'bag' of image slices, using attention scoring to identify the most important slices. An attention module helps the model focus on diagnostically relevant regions within each slice. The dataset comprised NCCT scans from 300 subjects, including 117 males and 183 females, with an average age of 52.5 ± 20.9 years, consisting of 132 normal cases and 168 cases of lung diseases, including 88 cases of CTEPH. The CNMIL framework was evaluated using sensitivity, specificity, and the area under the curve (AUC) metrics, and compared with common 3D supervised classification networks and existing CTEPH automatic diagnosis networks.Main results. The CNMIL framework demonstrated high diagnostic performance, achieving an AUC of 0.807, accuracy of 0.833, sensitivity of 0.795, and specificity of 0.849 in distinguishing CTEPH cases. Ablation studies revealed that integrating MIL and the CN significantly enhanced performance, with the model achieving an AUC of 0.978 and perfect sensitivity (1.000) in normal classification. Comparisons with other 3D network architectures confirmed that the integrated model outperformed others, achieving the highest AUC of 0.8419.Significance. The CNMIL network requires no additional scans or annotations, relying solely on NCCT. This approach can improve timely and accurate CTEPH detection, resulting in better patient outcomes.

Self-Administered Acupressure for Probable Knee Osteoarthritis in Middle-Aged and Older Adults: A Randomized Clinical Trial.

Importance: The effects of self-administered acupressure (SAA) on knee osteoarthritis (OA) pain remain unclear. Objective: To evaluate the effectiveness of SAA taught via a short training course on reducing knee OA pain in middle-aged and older adults. Design, Setting, and Participants: This randomized clinical trial was conducted among community-dwelling individuals in Hong Kong who were aged 50 years or older with probable knee OA from September 2019 to May 2022. Interventions: The intervention included 2 training sessions for SAA with a brief knee health education (KHE) session, in which participants practiced acupressure twice daily for 12 weeks. The control group (KHE only) received only education about maintaining knee health on the same schedule and duration. Main Outcomes and Measures: The primary outcome was the numerical rating scale (NRS) pain score at 12 weeks. Other outcomes included Western Ontario and McMaster University Osteoarthritis Index, Short Form 6 Dimensions (SF-6D), Timed Up and Go, and Fast Gait Speed tests. Results: A total of 314 participants (mean [SD] age, 62.7 [4.5] years; 246 [78.3%] female; mean [SD] knee pain duration, 7.3 [7.6] years) were randomized into intervention and KHE-only groups (each 157). At week 12, compared with the KHE-only group, the intervention group had a significantly greater reduction in NRS pain score (mean difference [MD], -0.54 points; 95% CI, -0.97 to -0.10 points; P = .02) and higher enhancement in SF-6D utility score (MD, 0.03 points; 95% CI, 0.003 to 0.01 points; P = .03) but did not have significant differences in other outcome measures. The cost-effectiveness acceptability curve demonstrated a greater than 90% probability that the intervention is cost-effective at a willingness to pay threshold of 1 GDP per capita. Conclusions and Relevance: In this randomized clinical trial, SAA with a brief KHE program was efficacious and cost-effective in relieving knee pain and improving mobility in middle-aged and older adults with probable knee OA. Trial Registration: ClinicalTrials.gov Identifier: NCT04191837.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease.

Whether higher serum phosphorus levels are associated with a higher risk for death and/or progression of chronic kidney disease (CKD) is not well established, and whether the association is confounded by access and barriers to care is unknown. To answer these questions, data of 10,672 individuals identified to have CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) from those participating in a community-based screening program were analyzed. Over a median follow-up of 2.3 years, there was no association between quartiles of serum phosphorus and all-cause mortality (adjusted hazards ratio for serum phosphorus over 3.3 to 3.7, over 3.7 to 4.1, and over 4.1 mg/dl, respectively: 1.22 (0.95-1.56), 1.00 (0.76-1.32), and 1.00 (0.75-1.33); reference, serum phosphorus of 3.3 mg/dl and below). Individuals in the highest quartile for serum phosphorus had a significantly higher risk for progression to end-stage renal disease (ESRD) (unadjusted hazards ratio, 6.72 (4.16-10.85)); however, the risk became nonsignificant on adjustment for potential confounders. There was no appreciable change in hazards ratio with inclusion of variables related to access and barriers to care. Additional analyses in subgroups based on 12 different variables yielded similar negative associations. Thus, in the largest cohort of individuals with early-stage CKD to date, we could not validate an independent association of serum phosphorus with risk for death or progression to ESRD.

The synergistic relationship between estimated GFR and microalbuminuria in predicting long-term progression to ESRD or death in patients with diabetes: results from the Kidney Early Evaluation Program (KEEP).

INTRODUCTION: Chronic kidney disease may complicate diabetes, often manifesting with reduced glomerular filtration rate (GFR), albuminuria, or both. Although greater albuminuria and lower estimated GFR both predict adverse prognosis, whether a synergistic prognostic interaction occurs in patients with diabetes has not been defined in a large national cohort study. METHODS: We used 2000-2011 data from the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) for 42,761 participants with diabetes. Kaplan-Meier survival analysis and multivariable Cox regression were used to ascertain the association of estimated GFR, albumin-creatinine ratio (ACR), and their interaction on all-cause mortality and progression to end-stage renal disease (ESRD) at a median 4 years of follow-up. RESULTS: Of 42,761 participants with diabetes, 8,618 (20.2%) had estimated GFR <60 mL/min/1.73 m(2), 7,715 (18.0%) had ACR >30 mg/g, and 2,641 (6.2%) had both. The unadjusted incidence (per 1,000 person-years) of all-cause mortality increased from 3.1 (95% CI, 2.4-3.8) in participants with estimated GFR ≥ 105 mL/min/1.73 m(2) and no albuminuria to 73.7 (95% CI, 54.9-92.5) in participants with estimated GFR <30 mL/min/1.73 m(2) and macroalbuminuria (P < 0.001). Progression to ESRD likewise increased from 0.2 (95% CI, 0-0.4) to 220.4 (95% CI, 177.2-263.6) per 1,000 person-years (P < 0.001). After adjustment for confounders, both estimated GFR and albuminuria were associated independently with mortality and progression to ESRD, with a strong synergistic interaction (P for interaction < 0.001); estimated GFR <30 mL/min/1.73 m(2) and macroalbuminuria together were associated with a 5-fold higher risk of mortality and a more than 1,000-fold higher risk of progression to ESRD (compared with patients with estimated GFR >60 mL/min/1.73 m(2) and ACR <30 mg/g; P < 0.001 for both outcomes). CONCLUSIONS: In this large cohort of diabetic KEEP participants with more than 170,000 person-years of follow-up, both estimated GFR and albuminuria were associated independently with mortality and progression to ESRD, with a strong synergistic interaction.

Association of race and body mass index with ESRD and mortality in CKD stages 3-4: results from the Kidney Early Evaluation Program (KEEP).

BACKGROUND: A recent cross-sectional analysis of Kidney Early Evaluation Program (KEEP) participants suggested that obesity is a heterogeneous disease state in African Americans and whites with chronic kidney disease (CKD). STUDY DESIGN: In longitudinal analyses spanning 8 years of follow-up, we examined whether race and body mass index (BMI) influence end-stage renal disease (ESRD) and mortality rates in participants with CKD stages 3-4. SETTING & PARTICIPANTS: KEEP participants were included in this analysis if they met the following criteria: (1) estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m(2), (2) white or African American race, and (3) no previous dialysis or transplantation. OUTCOMES & MEASUREMENTS: Survival analyses were performed for the outcomes of ESRD, death, and combined outcome of ESRD or death. RESULTS: Of 14,631 participants with CKD stages 3-4, 28% were African American and 72% were white. African American participants had higher rates of obesity and hypertension, with a higher baseline mean eGFR, higher prevalence of albuminuria, and greater degree of anemia compared with whites. In multivariable models, African American race increased the risk of ESRD (HR, 1.66; 95% CI, 1.26-2.07), but not death (HR, 0.89; 95% CI, 0.76-1.03). In these models, male sex, hypertension, diabetes, lower baseline eGFR, and albuminuria were predictive of higher rates of ESRD; age, male sex, diabetes, lower baseline eGFR, and albuminuria were predictive of overall mortality. There was no significant interaction between race and BMI in the adjusted model for outcomes of ESRD (P = 0.7) or death (P = 0.3). LIMITATIONS: Baseline values used in the analysis are from a cross-sectional data set. Dyslipidemia and secondary hyperparathyroidism were not accounted for in the analysis. CONCLUSIONS: African American race was associated with a higher incidence of ESRD, but not mortality. Although obesity may be a heterogeneous disease state in African Americans and whites with CKD, there does not appear to be a significant interaction between race and BMI in progression to ESRD or death.