A phase 1-2 trial of DA-EPOCH-R plus ixazomib for MYC-aberrant lymphoid malignancies: the DACIPHOR regimen.

ABSTRACT: MYC-aberrant non-Hodgkin lymphoma (NHL) is associated with poor outcomes with conventional chemotherapy. Ixazomib is an orally bioavailable proteasome inhibitor that targets drivers of MYC expression and has demonstrated preclinical activity in aggressive MYC-aberrant NHL. We conducted a phase 1/2 study evaluating the safety and efficacy of DA-EPOCH-R with adjunctive ixazomib in aggressive MYC-aberrant NHL. For induction, patients received 6 cycles of DA-EPOCH-R with ixazomib administered twice per 21-day cycle; responders continued weekly ixazomib maintenance for up to 1 year. Primary objectives were to determine the maximum tolerated dose in phase 1 and efficacy of DA-EPOCH-R with ixazomib as measured by 12-month progression-free survival (PFS) rate in phase 2. Thirty-six patients were evaluable for response. Median age was 63 years (range, 31-77) and 44% had double-hit lymphoma (DHL)/triple-hit lymphoma (THL). In phase 1, 3 mg of ixazomib was established as recommended phase 2 dose. Twenty-nine (76.3%) patients completed 6 cycles of DA-EPOCH-R and 25 (65.8%) underwent dose escalations. The ORR after induction was 97% (95% confidence interval, 81-100) with a CR rate of 69%. At median follow-up of 18.8 months, the 12-month PFS and overall survival (OS) rates were 78% and 86%, respectively. For DHL/THL vs dual expressor lymphomas (DEL), 12-month PFS rates were 53% vs 95% and 12-month OS rates were 65% vs 100%, respectively. Grade ≥3 toxicities were predominantly hematologic. Twenty-seven (75%) of patients experienced neuropathy, nearly all low-grade. DA-EPOCH-R induction with adjunctive ixazomib is feasible and appears effective in patients with DEL. This trial was registered at www.clinicaltrials.gov as #NCT02481310.

Selective dysfunction of the crural diaphragm in patients with chronic restrictive and obstructive lung disease.

BACKGROUND: Gastroesophageal reflux (GER) is known to be associated with chronic lung diseases. The driving force of GER is the transdiaphragmatic pressure (Pdi) generated mainly by costal and crural diaphragm contraction. The latter also enhances the esophagogastric junction (EGJ) pressure to guard against GER. METHODS: The relationship between Pdi and EGJ pressure was determined using high resolution esophageal manometry in patients with interstitial lung disease (ILD, n = 26), obstructive lung disease (OLD, n- = 24), and healthy subjects (n = 20). KEY RESULTS: The patient groups did not differ with respect to age, gender, BMI, and pulmonary rehabilitation history. Patients with ILD had significantly higher Pdi but lower EGJ pressures as compared to controls and OLD patients (p < 0.001). In control subjects, the increase in EGJ pressure at all-time points during inspiration was greater than Pdi. In contrast, the EGJ pressure during inspiration was less than Pdi in 14 patients with ILD and 7 patients with OLD. The drop in EGJ pressure was usually seen after the peak Pdi in ILD group (p < 0.0001) and before the peak Pdi in OLD group, (p = 0.08). Nine patients in the ILD group had sliding hiatus hernia, compared to none in control subjects (p = 0.003) and two patients in the OLD, (p = 0.04). CONCLUSIONS AND INFERENCES: A higher Pdi and low EGJ pressure, and dissociation between Pdi and EGJ pressure temporal relationship suggests selective dysfunction of the crural diaphragm in patients with chronic lung diseases and may explain the higher prevalence of GERD in ILD as seen in previous studies.

Misinterpreting cognitive change over multiple timepoints: When practice effects meet age-related decline.

OBJECTIVE: Practice effects (PE) on cognitive testing have been shown to delay detection of impairment and impede our ability to assess change. When decline over time is expected, as with older adults or progressive diseases, failure to adequately address PEs may lead to inaccurate conclusions because PEs artificially boost scores while pathology- or age-related decline reduces scores. Unlike most methods, a participant-replacement approach can separate pathology- or age-related decline from PEs; however, this approach has only been used across two timepoints. More than two timepoints make it possible to determine if PEs level out after the first follow-up, but it is analytically challenging because individuals may not be assessed at every timepoint. METHOD: We examined 1,190 older adults who were cognitively unimpaired (n = 809) or had mild cognitive impairment (MCI; n = 381). Participants completed six neuropsychological measures at three timepoints (baseline, 12-month, 24-month). We implemented a participant-replacement method using generalized estimating equations in comparisons of matched returnees and replacements to calculate PEs. RESULTS: Without accounting for PEs, cognitive function appeared to improve or stay the same. However, with the participant-replacement method, we observed significant PEs within both groups at all timepoints. PEs did not uniformly decrease across time; some-specifically on episodic memory measures-continued to increase beyond the first follow-up. CONCLUSION: A replacement method of PE adjustment revealed significant PEs across two follow-ups. As expected in these older adults, accounting for PEs revealed cognitive decline. This, in turn, means earlier detection of cognitive deficits, including progression to MCI, and more accurate characterization of longitudinal change. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Post-hoc power analysis: a conceptually valid approach for power based on observed study data.

Power analysis is a key component of planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences request power analysis for data already collected and analysed before accepting manuscripts for publication. Many have raised concerns about the conceptual basis for such post-hoc power analyses. More recently, Zhang et al showed by using simulation studies that such power analyses do not indicate true power for detecting statistical significance since post-hoc power estimates vary in the range of practical interests and can be very different from the true power. On the other hand, journals' request for information about the reliability of statistical findings in a manuscript due to small sample sizes is justified since the sample size plays an important role in the reproducibility of statistical findings. The problem is the wording of the journals' request, as the current power analysis paradigm is not designed to address journals' concerns about the reliability of the statistical findings. In this paper, we propose an alternate formulation of power analysis to provide a conceptually valid approach to the journals' wrongly worded but practically significant concern.

Comparison of the APAS Independence Automated Plate Reader System with the Manual Standard of Care for Processing Urine Culture Specimens.

Urine cultures are among the highest-volume tests in clinical microbiology laboratories and usually require considerable manual labor to perform. We evaluated the APAS Independence automated plate reader system and compared it to our manual standard of care (SOC) for processing urine cultures. The APAS device provides automated image interpretation of urine culture plate growth and sorts those images that require further evaluation. We examined 1,519 specimens over a 4-month period and compared the APAS growth interpretations to our SOC. We found that 72 of the 1,519 total specimens (4.74%) had growth discrepancies, where these specimens were interpreted differently by the APAS and the technologist, which required additional evaluation of plate images on the APAS system. Overall, there were 56 discrepancies in pathogen identification, which were present in 3.69% of the cultures. An additional pathogen was uncovered in a majority of these discrepancies; 12 (21.4%) identified an additional pathogen for the SOC, and 40 (71.4%) identified an additional pathogen for the APAS workflow. We found 214 (2.69%) antimicrobial susceptibility test (AST) discrepancies; 136 (1.71%) minor errors (mEs), 41 (0.52%) major errors (MEs), and 36 (0.45%) very major errors (VMEs). Many of the MEs and VMEs occurred in only a small subset of 13 organisms, suggesting that the specimen may have had different strains of the same pathogens with differing AST results. Given the significant labor required to perform urine cultures, the APAS Independence system has the potential to reduce manual labor while maintaining the identity and AST results of urinary pathogens. IMPORTANCE Urine cultures are among the highest-volume tests performed in clinical microbiology facilities and require considerable manual labor to perform. We compared the results of our manual SOC workflow with that of the APAS Independence system, which provides automated image interpretation and sorting of urine culture plates based on growth. We examined 1,519 urine cultures processed using both workflows and found that only 4.74% had growth pattern discrepancies and 3.69% pathogen identification discrepancies. There was substantial agreement in AST results between workflows, with only 2.69% having discrepancies. Only 1.71% of the ASTs had mEs, 0.52% had MEs, and 0.45% had VMEs, with most of the MEs and VMEs belonging to a small subset of organisms. The APAS system significantly decreased manual urine culture processing, while providing similar results to the SOC. As such, incorporating such automation into laboratory workflows has the potential to significantly improve efficiency.

Fitbit Use and Activity Levels From Intervention to 2 Years After: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: There has been a rapid increase in the use of commercially available activity trackers, such as Fitbit, in physical activity intervention research. However, little is known about the long-term sustained use of trackers and behavior change after short-term interventions. OBJECTIVE: This study aims to use minute-level data collected from a Fitbit tracker for up to 2 years after the end of a randomized controlled trial to examine patterns of Fitbit use and activity over time. METHODS: Participants in this secondary data analysis were 75 female breast cancer survivors who had been enrolled in a 12-week physical activity randomized controlled trial. Participants randomized to the exercise intervention (full intervention arm) received a Fitbit One, which was worn daily throughout the 12-week intervention, and then were followed for 2 years after the intervention. Participants randomized to the waitlist arm, after completing the randomized controlled trial, received a Fitbit One and a minimal version of the exercise intervention (light intervention arm), and then were followed for 2 years after the intervention. Average and daily adherence and MVPA were compared between the 2 groups in the interventional and postinterventional periods using both linear and generalized additive mixed effects models. RESULTS: Adherence to wearing the Fitbit during the 12-week intervention period was significantly higher in the full intervention arm than in the light intervention arm (85% vs 60%; P<.001). Average adherence was significantly lower for both study arms during the follow-up period than in the intervention period; however, there were statistically different patterns of adherence during the follow-up period, with the light intervention arm having steeper declines than the full intervention arm over time (P<.001). Similar to the adherence results, mean minutes of Fitbit-measured MVPA was higher for the full intervention arm than for the light intervention arm during the 12-week intervention period (mean MVPA 27.89 minutes/day, SD 16.38 minutes/day vs 18.35 minutes/day, SD 12.64 minutes/day; P<.001). During the follow-up period, average MVPA was significantly lower than the 12-week intervention period for both the full intervention arm (21.74 minutes/day, SD 24.65 minutes/day; P=.002) and the light intervention arm (15.03 minutes/day, SD 13.27 minutes/day; P=.004). Although the mean MVPA in each arm was similar across the follow-up period (P=.33), the pattern of daily MVPA was significantly different between the 2 groups (P<.001). CONCLUSIONS: While adherence to wearing activity trackers and maintaining physical activities declined after completion of a 12-week exercise intervention, a more active interventional strategy resulted in greater wear time and activity levels during the intervention and more stable patterns of adherence and activity in the long term. An improved understanding of long-term maintenance patterns may inform improved exercise interventions that result in sustained increases in physical activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02332876; https://clinicaltrials.gov/ct2/show/NCT02332876.

What is the impact of restricted access policy on workplace violence in general hospital? A before-after study in a CHINESE tertiary hospital.

BACKGROUND: To evaluate the impact of a restricted access policy on workplace violence in a healthcare setting. METHODS: We surveyed healthcare workers before and after the implementation of a restricted-access policy at a tertiary hospital in north-eastern China. Data were collected in April 2017 and January 2019. Fisher's exact test were used to compare the difference in workplace violence prevalence between responses to two surveys. Survey 1 (S1) collected data from 345 healthcare professionals who had worked in the inpatient ward for at least 12 months. Survey 2 (S2) included 338 healthcare workers from the same ward who had been employed for more than two years. The effective response rates for the two studies was 79.31 and 83.25%, respectively. All 18 female security guards were included in the investigation in S2. RESULTS: The prevalence of psychological violence was 62.03% in S1 and 34.62% in S2, the difference in prevalence showing statistical significance (P = 0.000), while the prevalence of physical violence was 3.77 and 4.73% respectively, showing no statistical significance (P = 0.573). The change in the rate of injury caused by physical violence was also statistically significant at 76.92 and 31.25% (P = 0.025), respectively. Security guards were at high risk of workplace violence under the policy. Most healthcare professionals thought this policy ameliorated treatment order, the sense of security, anxiety about workplace violence, and so forth, but one-third of the respondents thought that it caused patient dissatisfaction. CONCLUSION: While the restricted access policy may be effective for healthcare professionals in avoiding or dealing with violence, such policy could contribute to new problems regarding the safety of security guards and the potential dissatisfaction of patients. The policy should be further developed to alleviate this phenomenon.

Workplace violence against healthcare professionals in a multiethnic area: a cross-sectional study in southwest China.

OBJECTIVE: The purpose of this study is to examine workplace violence (WPV) towards healthcare professionals in a multiethnic area in China, including prevalence, influencing factors, healthcare professionals' response to WPV, expected antiviolence training measures and content, and evaluation of WPV interventions. DESIGN: A cross-sectional study. SETTING: A grade III, class A hospital in the capital of Yunnan Province, which is the province with the most diverse ethnic minority groups in China. PARTICIPANTS: In total, 2036 healthcare professionals participated, with a response rate of 83.79%. RESULTS: The prevalence of physical and psychological violence was 5.5% and 43.7%, respectively. Healthcare professionals of ethnic minority were more likely to experience psychological violence (OR=1.54, 95% CI 1.16 to 2.05). Stratified by gender, male healthcare professionals of ethnic minority suffered from more physical violence (OR=3.31, 95% CI 1.12 to 9.79), while female healthcare professionals suffered from psychological violence (OR=1.71, 95% CI 1.24 to 2.36). We also found a unique work situation in China: overtime duty on-call work (18:00-07:00) was a risk factor for psychological violence (OR=1.40, 95% CI 1.02 to 1.93). Healthcare professionals of ethnic minority are less likely to order perpetrators to stop or to report to superiors when faced with psychological violence. They are also more interested in receiving training in force skills and self-defence. Both Han and ethnic minority participants considered security measures as the most useful intervention, while changing the time of shift the most useless one. CONCLUSION: Our study comprehensively described WPV towards healthcare professionals in a multiethnic minority area. More research on WPV conducted in multiethnic areas is needed.

Primary health institutions preference by hypertensive patients: effect of distance, trust and quality of management in the rural Heilongjiang province of China.

BACKGROUND: Traditional "inverted triangle" healthcare resources allocation model in China has wasted a lot of health resources. The Chinese health reform began to strengthens the role of the primary health institutions in delivering primary health care especially in rural areas in the background of large development gap between urban-rural health and rapid growth in the incidence of chronic diseases in rural. We take hypertensive patients as an example, to verify the effect of policy implementation through distribution characteristics of rural primary health institutions preference of hypertensive patients and explore the influencing factor that promoting rationalized use of medical care for patients with chronic disease as well as rational allocation of health resources in rural areas. METHODS: A cross-sectional survey was conducted in Heilongjiang, a province in northeastern China by using a self-designed questionnaire. Stratified cluster sampling was used to choose 484 hypertensive patients from two villages in Heilongjiang province in 2010. RESULTS: About 88.4% of respondents reported preferred primary health institutions (83.5% preferred village clinics and 4.9% preferred township hospitals), 49.4% of respondents knew hypertension management administered by primary health institutions, 53.5% received hypertension education from primary care physicians, more than half of respondents reported that they didn't receive telephone interviews and family visits from primary care physicians over the past 6 months. Residence closer to the primary health institutions (OR = 10.360), trust in village doctors (OR = 7.323), elders (OR = 3.001), and asked for return visits by primary health physicians (OR = 2.073) promote preferences for primary health institutions. CONCLUSIONS: Accessibility to primary healthcare and doctor-patient trust stimulate patients to choose the primary health institutions. Primary health institutions should improve general approach to hypertension management and enhance the ability of providing basic public health services.

Vaccine confidence in China after the Changsheng vaccine incident: a cross-sectional study.

BACKGROUND: China's achievements in immunization are being threatened by a vaccine crisis. This paper aims to investigate vaccine confidence in China after the Changsheng vaccine incident and attempts to identify the factors contributing to it. METHODS: An online cross-sectional investigation was conducted from 1 to 25 September 2018. Descriptive analysis and logistic regression were performed to examine the associations between socio-demographic factors, cognition and attitudes towards the Changsheng vaccine incident and vaccine confidence. RESULTS: We included 1115 respondents in the final analysis, and found that approximately 70% (783) of the respondents did not have vaccine confidence. More than half of the respondents (54.53%) were dissatisfied with the government's response measures to the Changsheng vaccine incident. The logistic regression model indicated that vaccine confidence was positively associated with the degree of satisfaction with the government's response measures (OR = 1.621, 95% CI = 1.215-2.163), attitudes towards the risks and benefits of vaccination (OR = 1.501, 95% CI = 1.119-2.013), concerns about vaccine safety (OR = 0.480, 95% CI = 0.317-0.726), and vaccine efficacy (OR = 0.594, 95% CI = 0.394-0.895). CONCLUSIONS: A majority of the respondents held negative attitudes towards vaccines after the Changsheng vaccine incident. A coordinated effort is required to restore public confidence in vaccines, especially in China, where a nationwide mandatory immunization policy is implemented. To end dissent towards inoculation, a series of actions is crucial and multiple parties should work together to advance efforts and explore the possibility of establishing an open and transparent regulatory system.

Cancer prevalence among the rural poverty-stricken population in Northeast China.

Purpose: The burden of cancer impacts many of the world's top concerns, but little information is published about the characteristics of cancer prevalence in the poor population. Materials and methods: Data on cancer prevalence were obtained from the Health Poverty Alleviation Information System of Heilongjiang province. Prevalence was defined as all living cancer cases on October 1, 2018. Geographical area, cancer site, sex, age, educational level, and time since diagnosis were investigated. Results: There were 10,529 cancer cases among 624,869 poor rural people in Heilongjiang up to October 1, 2018, and 77% of them did not have labor ability. Females accounted for 53.4%. The top five common cancers were lung, breast, colorectal, stomach, and liver cancer. There were distinct regional, sex, and age distribution differences in cancers. The prevalence rate for overall cancers was 1,685.0 per 100,000 people, which was much higher than that of the national level. Cancer prevalence peaked at an earlier age group (65-69 year). The 5-year cancer prevalence was 80.1% of the total cases. Conclusion: Cancer imposes significant health and financial burdens in the rural poor. This study presents total and partial prevalence for the first time using actual dates from a large poor population in China, providing valuable information for tailored cancer prevention and control, quantifying the cancer burden and identifying priorities for poverty alleviation plans.

Leveraging marginal structural modeling with Cox regression to assess the survival benefit of accepting vs declining kidney allograft offers.

Existing studies evaluating the survival benefit of kidney transplantation were unable to incorporate time-updated information on decisions related to each organ offer. We used national registry data, including organ turndown data, to evaluate the survival benefit of accepting vs turning down kidney offers in candidates waitlisted from 2007-2013. Among candidates who declined their first offer, only 43% ultimately received organ transplantations. Recipients who later underwent organ transplantation after declining their first offer had markedly longer wait times than recipients who accepted their first offer, and 56% received kidney transplants that were of similar or lower quality compared to their initial offer. In marginal structural modeling analyses accounting for time-updated offer characteristics (including Kidney Donor Profile Index, Public Health System risk status, and pumping), after 3 months posttransplant, there was a significant survival benefit of accepting an offer (adjusted hazard ratio 0.76, 95% confidence interval 0.66-0.89) that was similar among diabetics, candidates aged >65 years, and candidates living in donor service areas with the longest waitlist times. After carefully accounting for the effect of donor quality, we confirm that the survival benefit of accepting an organ offer is clinically meaningful and persistent beyond 3 months post-kidney transplantation, including high-risk subgroups of organ transplantation candidates.

Catastrophic health expenditure incidence and its equity in China: a study on the initial implementation of the medical insurance integration system.

BACKGROUND: By 2013, several regions in China had introduced health insurance integration policies. However, few studies addressed the impact of medical insurance integration in China. This study investigates the catastrophic health expenditure and equity in the incidence of catastrophic health expenditure by addressing its potential determinants in both integrated and non-integrated areas in China in 2013. METHODS: The primary data are drawn from the fifth China National Health Services Survey in 2013. The final sample comprises 19,788 households (38.4%) from integrated areas and 31,797 households (61.6%) from non-integrated areas. A probit model is employed to decompose inequality in the incidence of catastrophic health expenditure in line with the methodology used for decomposing the concentration index. RESULTS: The incidence of catastrophic health expenditure in integrated areas is higher than in non-integrated areas (13.87% vs. 13.68%, respectively). The concentration index in integrated areas and non-integrated areas is - 0.071 and - 0.073, respectively. Average household out-of-pocket health expenditure and average capacity to pay in integrated areas are higher than those in non-integrated areas. However, households in integrated areas have lower share of out-of-pocket expenditures in the capacity to pay than households in non-integrated areas. The majority of the observed inequalities in catastrophic health expenditure can be explained by differences in the health insurance and householders' educational attainment both in integrated areas and non-integrated areas. CONCLUSIONS: The medical insurance integration system in China is still at the exploratory stage; hence, its effects are of limited significance, even though the positive impact of this system on low-income residents is confirmed. Moreover, catastrophic health expenditure is associated with pro-poor inequality. Medical insurance, urban-rural disparities, the elderly population, and use of health services significantly affect the equity of catastrophic health expenditure incidence and are key issues in the implementation of future insurance integration policies.