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Nevin Manimala Statistics

Alternative stable states, nonlinear behavior, and predictability of microbiome dynamics

Microbiome. 2023 Mar 29;11(1):63. doi: 10.1186/s40168-023-01474-5.

ABSTRACT

BACKGROUND: Microbiome dynamics are both crucial indicators and potential drivers of human health, agricultural output, and industrial bio-applications. However, predicting microbiome dynamics is notoriously difficult because communities often show abrupt structural changes, such as “dysbiosis” in human microbiomes.

METHODS: We integrated theoretical frameworks and empirical analyses with the aim of anticipating drastic shifts of microbial communities. We monitored 48 experimental microbiomes for 110 days and observed that various community-level events, including collapse and gradual compositional changes, occurred according to a defined set of environmental conditions. We analyzed the time-series data based on statistical physics and non-linear mechanics to describe the characteristics of the microbiome dynamics and to examine the predictability of major shifts in microbial community structure.

RESULTS: We confirmed that the abrupt community changes observed through the time-series could be described as shifts between “alternative stable states” or dynamics around complex attractors. Furthermore, collapses of microbiome structure were successfully anticipated by means of the diagnostic threshold defined with the “energy landscape” analysis of statistical physics or that of a stability index of nonlinear mechanics.

CONCLUSIONS: The results indicate that abrupt microbiome events in complex microbial communities can be forecasted by extending classic ecological concepts to the scale of species-rich microbial systems. Video Abstract.

PMID:36978146 | DOI:10.1186/s40168-023-01474-5

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Nevin Manimala Statistics

The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy

Breast Cancer Res. 2023 Mar 28;25(1):32. doi: 10.1186/s13058-023-01619-2.

ABSTRACT

BACKGROUND: Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient’s pathologic complete response (pCR) rate. Herein, we analyzed the predictive value of DTCs for the response to NACT and interrogated whether neoadjuvant denosumab treatment may eradicate DTCs in the bone marrow.

METHODS: A total of 167 patients from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive patients were re-analyzed for DTCs after NACT ± denosumab.

RESULTS: At baseline, DTCs were observed in 43/167 patients (25.7%) in the total cohort, however their presence did not predict response to nab-paclitaxel based NACT (pCR rates: 37.1% in DTC-negative vs. 32.6% DTC-positive; p = 0.713). Regarding breast cancer subtypes, the presence of DTCs at baseline was numerically associated with response to NACT in TNBC patients (pCR rates: 40.0% in DTC-positive vs. 66.7% in DTC-negative patients; p = 0.16). Overall, denosumab treatment did not significantly increase the given DTC-eradication rate of NACT (NACT: 69.6% DTC-eradication vs. NACT + denosumab: 77.8% DTC-eradication; p = 0.726). In TNBC patients with pCR, a numerical but statistically non-significant increase of DTC-eradication after NACT + denosumab was observed (NACT: 75% DTC-eradication vs. NACT + denosumab: 100% DTC-eradication; p = 1.00).

CONCLUSION: This is the first study worldwide, demonstrating that neoadjuvant add-on denosumab over a short-term period of 24 months does not increase the DTC-eradication rate in breast cancer patients treated with NACT.

PMID:36978142 | DOI:10.1186/s13058-023-01619-2

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Nevin Manimala Statistics

Rugby Fans in Training New Zealand (RUFIT NZ): a randomized controlled trial to assess the effectiveness of a healthy lifestyle program for overweight men delivered through professional rugby clubs

Int J Behav Nutr Phys Act. 2023 Mar 28;20(1):37. doi: 10.1186/s12966-022-01395-w.

ABSTRACT

BACKGROUND: A healthy lifestyle program that appeals to, and supports, overweight and obese New Zealand (NZ) European, Māori (indigenous) and Pasifika men to achieve weight loss is urgently needed. A pilot program inspired by the successful Football Fans in Training program but delivered via professional rugby clubs in NZ (n = 96) was shown to be effective in weight loss, adherence to healthy lifestyle behaviors, and cardiorespiratory fitness in overweight and obese men. A full effectiveness trial is now needed.

AIMS: To determine the effectiveness and cost effectiveness of Rugby Fans In Training-NZ (RUFIT-NZ) on weight loss, fitness, blood pressure, lifestyle change, and health related quality of life (HRQoL) at 12- and 52-weeks.

METHODS: We conducted a pragmatic, two-arm, multi-center, randomized controlled trial in NZ with 378 (target 308) overweight and obese men aged 30-65 years, randomized to an intervention group or wait-list control group. The 12-week RUFIT-NZ program was a gender-sensitised, healthy lifestyle intervention delivered through professional rugby clubs. Each intervention session included: i) a 1-h workshop-based education component focused on nutrition, physical activity, sleep, sedentary behavior, and learning evidence-based behavior change strategies for sustaining a healthier lifestyle; and 2) a 1-h group-based, but individually tailored, exercise training session. The control group were offered RUFIT-NZ after 52-weeks. The primary outcome was change in body weight from baseline to 52-weeks. Secondary outcomes included change in body weight at 12-weeks, waist circumference, blood pressure, fitness (cardiorespiratory and musculoskeletal), lifestyle behaviors (leisure-time physical activity, sleep, smoking status, and alcohol and dietary quality), and health-related quality of life at 12- and 52-weeks.

RESULTS: Our final analysis included 200 participants (intervention n = 103; control n = 97) who were able to complete the RUFIT-NZ intervention prior to COVID-19 restrictions. At 52-weeks, the adjusted mean group difference in weight change (primary outcome) was -2.77 kg (95% CI -4.92 to -0.61), which favored the intervention group. The intervention also resulted in favorable significant differences in weight change and fruit and vegetable consumption at 12-weeks; and waist circumference, fitness outcomes, physical activity levels, and health-related quality of life at both 12 and 52 weeks. No significant intervention effects were observed for blood pressure, or sleep. Incremental cost-effective ratios estimated were $259 per kg lost, or $40,269 per quality adjusted life year (QALY) gained.

CONCLUSION: RUFIT-NZ resulted in sustained positive changes in weight, waist circumference, physical fitness, self-reported physical activity, selected dietary outcomes, and health-related quality of life in overweight/obese men. As such, the program should be recommended for sustained delivery beyond this trial, involving other rugby clubs across NZ.

TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry, ACTRN12619000069156. Registered 18 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376740 Universal Trial Number, U1111-1245-0645.

PMID:36978139 | DOI:10.1186/s12966-022-01395-w

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Nevin Manimala Statistics

Relationship between preoperative red blood cell distribution width and postoperative pneumonia in elderly patients with hip fracture: a retrospective cohort study

J Orthop Surg Res. 2023 Mar 28;18(1):253. doi: 10.1186/s13018-023-03732-6.

ABSTRACT

OBJECTIVE: The relationship between the preoperative red blood cell distribution width and postoperative pneumonia in elderly patients with hip fractures remains unclear. This study investigated whether the preoperative red blood cell distribution width was associated with postoperative pneumonia in elderly patients with hip fractures.

METHODS: Clinical data of patients with hip fractures in the Department of orthopedics of a hospital from January 2012 to December 2021 were retrospectively analyzed. A generalized additive model was used to identify both linear and nonlinear relationships between red blood cell distribution width and postoperative pneumonia. A two-piecewise linear regression model was used to calculate the saturation effect. Subgroup analyses were performed using stratified logistic regression.

RESULTS: This study included a total of 1444 patients. The incidence of postoperative pneumonia was 6.30% (91/1444), the mean age of the patients was 77.55 ± 8.75 years, and 73.06% of them (1055/1444) were female. After full adjustment for covariates, the preoperative red blood cell distribution width showed a nonlinear relationship with postoperative pneumonia. The two-piecewise regression model showed an inflection point at 14.3%. On the left side of the inflection point, the incidence of postoperative pneumonia increased by 61% for every 1% increase in red blood cell distribution width (OR: 1.61, 95% CI 1.13-2.31, P = 0.0089). The effect size was not statistically significant on the right side of the inflection point (OR: 0.83, 95% CI 0.61-1.12, P = 0.2171).

CONCLUSION: The relationship between preoperative red blood cell distribution width and incidence or postoperative pneumonia was nonlinear in elderly patients with hip fractures. The incidence of postoperative pneumonia was positively correlated with red blood cell distribution width when it was < 14.3%. A saturation effect was observed when the red blood cell distribution width reached 14.3%.

PMID:36978138 | DOI:10.1186/s13018-023-03732-6

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Effect of total cholesterol and statin therapy on mortality in ARDS patients: a secondary analysis of the SAILS and HARP-2 trials

Crit Care. 2023 Mar 28;27(1):126. doi: 10.1186/s13054-023-04387-9.

ABSTRACT

BACKGROUND: Two acute respiratory distress syndrome (ARDS) trials showed no benefit for statin therapy, though secondary analyses suggest inflammatory subphenotypes may have a differential response to simvastatin. Statin medications decrease cholesterol levels, and low cholesterol has been associated with increased mortality in critical illness. We hypothesized that patients with ARDS and sepsis with low cholesterol could be harmed by statins.

METHODS: Secondary analysis of patients with ARDS and sepsis from two multicenter trials. We measured total cholesterol from frozen plasma samples obtained at enrollment in Statins for Acutely Injured Lungs from Sepsis (SAILS) and Simvastatin in the Acute Respiratory Distress Syndrome (HARP-2) trials, which randomized subjects with ARDS to rosuvastatin versus placebo and simvastatin versus placebo, respectively, for up to 28 days. We compared the lowest cholesterol quartile (< 69 mg/dL in SAILS, < 44 mg/dL in HARP-2) versus all other quartiles for association with 60-day mortality and medication effect. Fisher’s exact test, logistic regression, and Cox Proportional Hazards were used to assess mortality.

RESULTS: There were 678 subjects with cholesterol measured in SAILS and 509 subjects in HARP-2, of whom 384 had sepsis. Median cholesterol at enrollment was 97 mg/dL in both SAILS and HARP-2. Low cholesterol was associated with higher APACHE III and shock prevalence in SAILS, and higher Sequential Organ Failure Assessment score and vasopressor use in HARP-2. Importantly, the effect of statins differed in these trials. In SAILS, patients with low cholesterol who received rosuvastatin were more likely to die (odds ratio (OR) 2.23, 95% confidence interval (95% CI) 1.06-4.77, p = 0.02; interaction p = 0.02). In contrast, in HARP-2, low cholesterol patients had lower mortality if randomized to simvastatin, though this did not reach statistical significance in the smaller cohort (OR 0.44, 95% CI 0.17-1.07, p = 0.06; interaction p = 0.22).

CONCLUSIONS: Cholesterol levels are low in two cohorts with sepsis-related ARDS, and those in the lowest cholesterol quartile are sicker. Despite the very low levels of cholesterol, simvastatin therapy seems safe and may reduce mortality in this group, though rosuvastatin was associated with harm.

PMID:36978134 | DOI:10.1186/s13054-023-04387-9

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Nevin Manimala Statistics

Repeatability and reproducibility of various 4D Flow MRI postprocessing software programs in a multi-software and multi-vendor cross-over comparison study

J Cardiovasc Magn Reson. 2023 Mar 28;25(1):22. doi: 10.1186/s12968-023-00921-4.

ABSTRACT

BACKGROUND: Different software programs are available for the evaluation of 4D Flow cardiovascular magnetic resonance (CMR). A good agreement of the results between programs is a prerequisite for the acceptance of the method. Therefore, the goal was to compare quantitative results from a cross-over comparison in individuals examined on two scanners of different vendors analyzed with four postprocessing software packages.

METHODS: Eight healthy subjects (27 ± 3 years, 3 women) were each examined on two 3T CMR systems (Ingenia, Philips Healthcare; MAGNETOM Skyra, Siemens Healthineers) with a standardized 4D Flow CMR sequence. Six manually placed aortic contours were evaluated with Caas (Pie Medical Imaging, SW-A), cvi42 (Circle Cardiovascular Imaging, SW-B), GTFlow (GyroTools, SW-C), and MevisFlow (Fraunhofer Institute MEVIS, SW-D) to analyze seven clinically used parameters including stroke volume, peak flow, peak velocity, and area as well as typically scientifically used wall shear stress values. Statistical analysis of inter- and intrareader variability, inter-software and inter-scanner comparison included calculation of absolute and relative error (ER), intraclass correlation coefficient (ICC), Bland-Altman analysis, and equivalence testing based on the assumption that inter-software differences needed to be within 80% of the range of intrareader differences.

RESULTS: SW-A and SW-C were the only software programs showing agreement for stroke volume (ICC = 0.96; ER = 3 ± 8%), peak flow (ICC: 0.97; ER = -1 ± 7%), and area (ICC = 0.81; ER = 2 ± 22%). Results from SW-A/D and SW-C/D were equivalent only for area and peak flow. Other software pairs did not yield equivalent results for routinely used clinical parameters. Especially peak maximum velocity yielded poor agreement (ICC ≤ 0.4) between all software packages except SW-A/D that showed good agreement (ICC = 0.80). Inter- and intrareader consistency for clinically used parameters was best for SW-A and SW-D (ICC = 0.56-97) and worst for SW-B (ICC = -0.01-0.71). Of note, inter-scanner differences per individual tended to be smaller than inter-software differences.

CONCLUSIONS: Of all tested software programs, only SW-A and SW-C can be used equivalently for determination of stroke volume, peak flow, and vessel area. Irrespective of the applied software and scanner, high intra- and interreader variability for all parameters have to be taken into account before introducing 4D Flow CMR in clinical routine. Especially in multicenter clinical trials a single image evaluation software should be applied.

PMID:36978131 | DOI:10.1186/s12968-023-00921-4

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Nevin Manimala Statistics

Machine learning prognosis model based on patient-reported outcomes for chronic heart failure patients after discharge

Health Qual Life Outcomes. 2023 Mar 29;21(1):31. doi: 10.1186/s12955-023-02109-x.

ABSTRACT

BACKGROUND: Patient-reported outcomes (PROs) can be obtained outside hospitals and are of great significance for evaluation of patients with chronic heart failure (CHF). The aim of this study was to establish a prediction model using PROs for out-of-hospital patients.

METHODS: CHF-PRO were collected in 941 patients with CHF from a prospective cohort. Primary endpoints were all-cause mortality, HF hospitalization, and major adverse cardiovascular events (MACEs). To establish prognosis models during the two years follow-up, six machine learning methods were used, including logistic regression, random forest classifier, extreme gradient boosting (XGBoost), light gradient boosting machine, naive bayes, and multilayer perceptron. Models were established in four steps, namely, using general information as predictors, using four domains of CHF-PRO, using both of them and adjusting the parameters. The discrimination and calibration were then estimated. Further analyze were performed for the best model. The top prediction variables were further assessed. The Shapley additive explanations (SHAP) method was used to explain black boxes of the models. Moreover, a self-made web-based risk calculator was established to facilitate the clinical application.

RESULTS: CHF-PRO showed strong prediction value and improved the performance of the models. Among the approaches, XGBoost of the parameter adjustment model had the highest prediction performance with an area under the curve of 0.754 (95% CI: 0.737 to 0.761) for death, 0.718 (95% CI: 0.717 to 0.721) for HF rehospitalization and 0.670 (95% CI: 0.595 to 0.710) for MACEs. The four domains of CHF-PRO, especially the physical domain, showed the most significant impact on the prediction of outcomes.

CONCLUSION: CHF-PRO showed strong prediction value in the models. The XGBoost models using variables based on CHF-PRO and the patient’s general information provide prognostic assessment for patients with CHF. The self-made web-based risk calculator can be conveniently used to predict the prognosis for patients after discharge.

CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn/index.aspx ; Unique identifier: ChiCTR2100043337.

PMID:36978124 | DOI:10.1186/s12955-023-02109-x

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Nevin Manimala Statistics

Association of the American Heart Association’s new “Life’s Essential 8” with all-cause and cardiovascular disease-specific mortality: prospective cohort study

BMC Med. 2023 Mar 29;21(1):116. doi: 10.1186/s12916-023-02824-8.

ABSTRACT

BACKGROUND: The American Heart Association recently updated its construct of what constitutes cardiovascular health (CVH), called Life’s Essential 8. We examined the association of total and individual CVH metrics according to Life’s Essential 8 with all-cause and cardiovascular disease (CVD)-specific mortality later in life.

METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 at baseline linked to the 2019 National Death Index records. Total and individual CVH metric scores including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure were classified as 0-49 (low level), 50-74 (intermediate level), and 75-100 (high level) points. The total CVH metric score (the average of the 8 metrics) as a continuous variable was also used for dose-response analysis. The main outcomes included all-cause and CVD-specific mortality.

RESULTS: A total of 19,951 US adults aged 30-79 years were included in this study. Only 19.5% of adults achieved a high total CVH score, whereas 24.1% had a low score. During a median follow-up of 7.6 years, compared with adults with a low total CVH score, those with an intermediate or high total CVH score had 40% (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.51-0.71) and 58% (adjusted HR 0.42, 95% CI 0.32-0.56) reduced risk of all-cause mortality. The corresponding adjusted HRs (95%CIs) were 0.62 (0.46-0.83) and 0.36 (0.21-0.59) for CVD-specific mortality. The population-attributable fractions for high (score ≥ 75 points) vs. low or intermediate (score < 75 points) CVH scores were 33.4% for all-cause mortality and 42.9% for CVD-specific mortality. Among all 8 individual CVH metrics, physical activity, nicotine exposure, and diet accounted for a large proportion of the population-attributable risks for all-cause mortality, whereas physical activity, blood pressure, and blood glucose accounted for a large proportion of CVD-specific mortality. There were approximately linear dose-response associations of total CVH score (as a continuous variable) with all-cause and CVD-specific mortality.

CONCLUSIONS: Achieving a higher CVH score according to the new Life’s Essential 8 was associated with a reduced risk of all-cause and CVD-specific mortality. Public health and healthcare efforts targeting the promotion of higher CVH scores could provide considerable benefits to reduce the mortality burden later in life.

PMID:36978123 | DOI:10.1186/s12916-023-02824-8

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Horse-riding hazards: an observational cohort study mapping equestrian related injuries at a Scandinavian trauma centre

BMC Sports Sci Med Rehabil. 2023 Mar 28;15(1):46. doi: 10.1186/s13102-023-00646-y.

ABSTRACT

INTRODUCTION: Horse-riding is practiced on a regular basis by 500,000 people in Sweden. It is reputed to be one of the most dangerous sports. On average, there were 1756 acute injuries and three fatalities each year between 1997 and 2014 in Sweden related to horses. The primary aim of this study was to outline the injury spectrum related to equestrian activities cared for at a large Swedish trauma centre. The secondary aim was to identify trends in clinical outcomes and to investigate the association between age and such outcomes.

MATERIAL AND METHODS: The electronic medical records system at Karolinska University Hospital was queried for patients cared for due to equestrian related trauma between July 2010 and July 2020. Complementary data were gathered using the hospital’s Trauma Registry. No exclusion criteria were applied. Descriptive statistics were used to outline the injury spectrum. Age was split into four categories which were compared using the Kruskal-Wallis H test or the Chi-squared test. Logistic regression was used to analyse correlations between age and outcomes.

RESULTS: A total of 3036 patients were included with 3325 injuries identified as equestrian related. The hospital admission rate was 24.9%. The cohort had one death. Regression analysis showed significant associations between decreasing risk of upper extremity injury (p < 0.001), increasing risk of vertebral fractures (p = 0.001) and increasing risk of thoracic injury (p < 0.001) with increasing age.

CONCLUSIONS: Equestrian activities are not without risks. The morbidity is high, and injuries are taken seriously by the medical profession, reflected by the high admission rate. There are age-related variations in the injury spectrum. Older age appears to predispose to vertebral fractures and thoracic injuries. Other factors than age appear more important in determining the need for surgery or admission to ICU.

PMID:36978116 | DOI:10.1186/s13102-023-00646-y

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Nevin Manimala Statistics

Metabolic syndrome among people living with HIV in Ethiopia: a systematic review and meta-analysis

Diabetol Metab Syndr. 2023 Mar 28;15(1):61. doi: 10.1186/s13098-023-01034-9.

ABSTRACT

BACKGROUND: Human Immuno-deficiency Virus (HIV) infection and antiretroviral therapy (ART) can cause metabolic disorders such as lipodystrophy, dyslipidemia, and insulin resistance, all of which are symptoms of metabolic syndrome (MetS). In Ethiopia, despite the existence of the primary studies, there was no pooled study conducted to summarize the country-level MetS among people living with HIV (PLHIV). Therefore, this study aims to estimate the pooled prevalence of MetS among PLHIV in Ethiopia.

METHODS: A systematic search was conducted to retrieve studies on the prevalence of MetS among PLHIV in Ethiopia from PubMed, Google Scholar, Science Direct, Web of Sciences, HINARI, and other relevant sources. A random-effects model was used to estimate the MetS in this study. The overall variation between studies was checked by the heterogeneity test (I2). The Joanna Briggs Institute (JBI) quality appraisal criteria were used to assess the quality of the studies. The summary estimates were presented with forest plots and tables. Publication bias was checked with the funnel plot and Egger’s regression test.

RESULTS: Overall, 366 articles were identified and evaluated using the PRISMA guidelines, with 10 studies meeting the inclusion criteria included in the final analysis. The pooled prevalence of MetS among PLHIV in Ethiopia was 21.7% (95% CI:19.36-24.04) using National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) and 29.91% (95% CI: 21.54-38.28) using International Diabetes Federation (IDF) criteria. The lowest and highest prevalence of MetS were 19.14% (95%CI: 15.63-22.64) and 25.6% (95%CI: 20.18-31.08) at Southern Nation and Nationality People Region (SNNPR) and Addis Ababa, respectively. There was no statistical evidence of publication bias in both NCEP-ATP III and IDF pooled estimates.

CONCLUSION: MetS was common among PLHIV in Ethiopia. Therefore, optimizing regular screening for MetS components and promoting a healthy lifestyle is suggested for PLHIV. Furthermore, more study is contributory to identify the barriers to implementing planned interventions and meeting recommended treatment goals.

TRIAL REGISTRATION: The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42023403786.

PMID:36978109 | DOI:10.1186/s13098-023-01034-9