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Nevin Manimala Statistics

Direct optimization of dose-volume histogram metrics in radiation therapy treatment planning

Biomed Phys Eng Express. 2020 Oct 1;6(6). doi: 10.1088/2057-1976/abb5ea.

ABSTRACT

We present a method of directly optimizing on deviations in clinical goal values in radiation therapy treatment planning. Using a new mathematical framework in which metrics derived from the dose-volume histogram are regarded as functionals of an auxiliary random variable, we are able to obtain volume-at-dose and dose-at-volume as infinitely differentiable functions of the dose distribution with easily evaluable function values and gradients. Motivated by the connection to risk measures in finance, which is formalized in this framework, we also derive closed-form formulas for mean-tail-dose and demonstrate its capability of reducing extreme dose values in tail distributions. Numerical experiments performed on a prostate and a head-and-neck patient case show that the direct optimization of dose-volume histogram metrics produced marginally better results than or outperformed conventional planning objectives in terms of clinical goal fulfilment, control of low- and high-dose tails of target distributions and general plan quality defined by a pre-specified evaluation measure. The proposed framework eliminates the disconnect between optimization functions and evaluation metrics and may thus reduce the need for repetitive user interaction associated with conventional treatment planning. The method also has the potential of enhancing plan optimization in other settings such as multicriteria optimization and automated treatment planning.

PMID:34035188 | DOI:10.1088/2057-1976/abb5ea

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Nevin Manimala Statistics

Determination of hypertension disease using chirp z-transform and statistical features of optimal band-pass filtered short-time photoplethysmography signals

Biomed Phys Eng Express. 2020 Nov 9;6(6). doi: 10.1088/2057-1976/abc634.

ABSTRACT

Hypertension is the condition where the normal blood pressure is high. This situation is manifested by the high pressure of the blood in the vein towards the vessel wall. Hypertension mostly affects the brain, kidneys, eyes, arteries and heart. Therefore, the diagnosis of this common disease is important. It may take days, weeks or even months for diagnosis. Often a device, called a blood pressure holter, is connected to the person for 24 or 48 h and the person’s blood pressure is recorded at certain intervals. Diagnosis can be made by the specialist physician considering these results. In recent years, various physiological measurement techniques have been used to accelerate this time-consuming diagnostic phase and intelligent models have been proposed. One of these techniques is photopletesmography (PPG). In this study, a model for the detection of hypertension disease in individuals was proposed using chirp z-transform and statistical features (total band power, autoregressive model parameters, standard deviation of signal’s derivative and zero crossing rate) of optimal band-pass filtered short-time PPG signals. The proposed method was successfully applied to 657 PPG trials, which each of them had only 2.1 s signal length and achieved a classification accuracy rate of 77.52% on the test data. The results showed that the diagnosis of hypertension can be performed effectively by chirp z-transform and statistical features and support vector machine classifier using optimal frequency range of 1.4-6 Hz.

PMID:34035194 | DOI:10.1088/2057-1976/abc634

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Nevin Manimala Statistics

Association between obesity and chronic rhinosinusitis with nasal polyps: a national population-based study

BMJ Open. 2021 May 25;11(5):e047230. doi: 10.1136/bmjopen-2020-047230.

ABSTRACT

OBJECTIVES: We performed a cross-sectional analysis of data from the nationwide Korea National Health and Nutrition Examination Survey to evaluate the association between obesity and chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyp (CRSsNP).

DESIGN: Retrospective cross-sectional analysis of health survey data.

SETTING: Voluntary survey of representative South Korean populations.

PARTICIPANTS: In total, 32 384 individuals aged 19 years or older with available data on CRS and obesity were included.

PRIMARY AND SECONDARY OUTCOME MEASURES: Diagnosis of CRSwNP or CRSsNP was performed by trained otolaryngologists through sinus endoscopy and surveys of medical history. General and central obesity was diagnosed using body mass index (BMI) and waist circumference (WC), respectively.

METHODS: A multivariate logistic regression analysis was used to clarify the association between CRSwNP or CRSsNP and obesity according to BMI and WC. Non-obese individuals were recruited as controls.

RESULTS: The prevalence of CRSwNP was higher in the general (OR, 1.438; 95% CI, 1.170 to 1.768; p<0.001) and central (OR, 1.251; 95% CI, 1.031 to 1.520; p=0.033) obesity groups than in the control group. Prevalence of CRSsNP was not correlated with obesity. In a logistic regression analysis, olfactory dysfunction (OR, 1.329; 95% CI, 1.137 to 1.553; p<0.001) and purulent discharge (OR, 1.383; 95% CI, 1.193 to 1.603; p<0.001) showed a higher incidence in the central obesity group than in the control group.

CONCLUSIONS: We demonstrated an association between CRSwNP and general and central obesity. Further investigations on the mechanism underlying this correlation are necessary for an improved understanding of the pathogenesis of CRSwNP.

PMID:34035104 | DOI:10.1136/bmjopen-2020-047230

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BOugie or stylet in patients UnderGoing Intubation Emergently (BOUGIE): protocol and statistical analysis plan for a randomised clinical trial

BMJ Open. 2021 May 25;11(5):e047790. doi: 10.1136/bmjopen-2020-047790.

ABSTRACT

INTRODUCTION: Intubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation.

METHODS AND ANALYSIS: The BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021.

ETHICS AND DISSEMINATION: The trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03928925).

PMID:34035106 | DOI:10.1136/bmjopen-2020-047790

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Trends in health expectancies: a systematic review of international evidence

BMJ Open. 2021 May 25;11(5):e045567. doi: 10.1136/bmjopen-2020-045567.

ABSTRACT

OBJECTIVES: A clear understanding of whether increases in longevity are spent in good health is necessary to support ageing, health and care-related policy.

DESIGN: We conducted a systematic review to update and summarise evidence on trends in health expectancies, in Organisation for Economic Co-operation and Development (OECD) high-income countries.

DATA SOURCES: Four electronic databases (MEDLINE, 1946-19 September 2019; Embase 1980-2019 week 38; Scopus 1966-22 September 2019, Health Management Information Consortium, 1979-September 2019), and the UK Office for National Statistics website (November 2019).

ELIGIBILITY CRITERIA: English language studies published from 2016 that reported trends in healthy, active and/or disability-free life expectancy in an OECD high-income country.

DATA EXTRACTION AND SYNTHESIS: Records were screened independently by two researchers. Study quality was assessed using published criteria designed to identify sources of bias in studies reporting trends, and evidence summarised by narrative synthesis.

FINDINGS: Twenty-eight publications from 11 countries were included, covering periods from 6 to 40 years, between 1970 and 2017. In most countries, gains in healthy and disability-free life expectancy do not match the growth in total life expectancy. Exceptions were demonstrated for women in Sweden, where there were greater gains in disability-free years than life expectancy. Gains in healthy and disability-free life expectancy were greater for men than women in most countries except the USA (age 85), Japan (birth), Korea (age 65) and Sweden (age 77).

CONCLUSION: An expansion of disability in later life is evident in a number of high-income countries, with implications for the sustainability of health and care systems. The recent COVID-19 pandemic may also impact health expectancies in the longer term.

PMID:34035101 | DOI:10.1136/bmjopen-2020-045567

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Multimodal measurement approach to identify individuals with mild cognitive impairment: study protocol for a cross-sectional trial

BMJ Open. 2021 May 25;11(5):e046879. doi: 10.1136/bmjopen-2020-046879.

ABSTRACT

INTRODUCTION: The diagnosis of mild cognitive impairment (MCI), that is, the transitory phase between normal age-related cognitive decline and dementia, remains a challenging task. It was observed that a multimodal approach (simultaneous analysis of several complementary modalities) can improve the classification accuracy. We will combine three noninvasive measurement modalities: functional near-infrared spectroscopy (fNIRS), electroencephalography and heart rate variability via ECG. Our aim is to explore neurophysiological correlates of cognitive performance and whether our multimodal approach can aid in early identification of individuals with MCI.

METHODS AND ANALYSIS: This study will be a cross-sectional with patients with MCI and healthy controls (HC). The neurophysiological signals will be measured during rest and while performing cognitive tasks: (1) Stroop, (2) N-back and (3) verbal fluency test (VFT). Main aims of statistical analysis are to (1) determine the differences in neurophysiological responses of HC and MCI, (2) investigate relationships between measures of cognitive performance and neurophysiological responses and (3) investigate whether the classification accuracy can be improved by using our multimodal approach. To meet these targets, statistical analysis will include machine learning approaches.This is, to the best of our knowledge, the first study that applies simultaneously these three modalities in MCI and HC. We hypothesise that the multimodal approach improves the classification accuracy between HC and MCI as compared with a unimodal approach. If our hypothesis is verified, this study paves the way for additional research on multimodal approaches for dementia research and fosters the exploration of new biomarkers for an early detection of nonphysiological age-related cognitive decline.

ETHICS AND DISSEMINATION: Ethics approval was obtained from the local Ethics Committee (reference: 83/19). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04427436, registered on 10 June 2020, https://clinicaltrials.gov/ct2/show/study/NCT04427436.

PMID:34035103 | DOI:10.1136/bmjopen-2020-046879

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Economic evaluation of robot-assisted training versus an enhanced upper limb therapy programme or usual care for patients with moderate or severe upper limb functional limitation due to stroke: results from the RATULS randomised controlled trial

BMJ Open. 2021 May 25;11(5):e042081. doi: 10.1136/bmjopen-2020-042081.

ABSTRACT

OBJECTIVE: To determine whether robot-assisted training is cost-effective compared with an enhanced upper limb therapy (EULT) programme or usual care.

DESIGN: Economic evaluation within a randomised controlled trial.

SETTING: Four National Health Service (NHS) centres in the UK: Queen’s Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust; Northwick Park Hospital, London Northwest Healthcare NHS Trust; Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde; and North Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust.

PARTICIPANTS: 770 participants aged 18 years or older with moderate or severe upper limb functional limitation from first-ever stroke.

INTERVENTIONS: Participants randomised to one of three programmes provided over a 12-week period: robot-assisted training plus usual care; the EULT programme plus usual care or usual care.

MAIN ECONOMIC OUTCOME MEASURES: Mean healthcare resource use; costs to the NHS and personal social services in 2018 pounds; utility scores based on EQ-5D-5L responses and quality-adjusted life years (QALYs). Cost-effectiveness reported as incremental cost per QALY and cost-effectiveness acceptability curves.

RESULTS: At 6 months, on average usual care was the least costly option (£3785) followed by EULT (£4451) with robot-assisted training being the most costly (£5387). The mean difference in total costs between the usual care and robot-assisted training groups (£1601) was statistically significant (p<0.001). Mean QALYs were highest for the EULT group (0.23) but no evidence of a difference (p=0.995) was observed between the robot-assisted training (0.21) and usual care groups (0.21). The incremental cost per QALY at 6 months for participants randomised to EULT compared with usual care was £74 100. Cost-effectiveness acceptability curves showed that robot-assisted training was unlikely to be cost-effective and that EULT had a 19% chance of being cost-effective at the £20 000 willingness to pay (WTP) threshold. Usual care was most likely to be cost-effective at all the WTP values considered in the analysis.

CONCLUSIONS: The cost-effectiveness analysis suggested that neither robot-assisted training nor EULT, as delivered in this trial, were likely to be cost-effective at any of the cost per QALY thresholds considered.

TRIAL REGISTRATION NUMBER: ISRCTN69371850.

PMID:34035087 | DOI:10.1136/bmjopen-2020-042081

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Association between dyslipidemia and risk of type 2 diabetes mellitus in middle-aged and older Chinese adults: a secondary analysis of a nationwide cohort

BMJ Open. 2021 May 25;11(5):e042821. doi: 10.1136/bmjopen-2020-042821.

ABSTRACT

AIMS: To evaluate the type 2 diabetes mellitus (T2DM) risk of individuals with different types of dyslipidaemia and compare the predictive value of distinct lipid parameters in predicting T2DM.

METHODS: We conducted a secondary analysis of data from the China Health and Retirement Longitudinal Study (CHARLS). 17 708 individuals over 45 years old were interviewed, and 11 847 blood samples were collected at the baseline survey (2011-2012). Outcome of T2DM was confirmed during two follow-up surveys (2013-2014 and 2015-2016). The HRs and 95% CI of T2DM associated with dyslipidaemia were estimated by Cox proportional hazards regressions model. The discriminatory value of eight lipid parameters were compared by the area under the receiver operating characteristic (ROC) curve (AUC).

RESULTS: A total of 7329 participants were enrolled in our analysis; during the mean follow-up time of 3.4 years, 387 (5.28%) participants developed new-onset diabetes. Compared with participants in normal lipid levels, the T2DM risk of those with hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein cholesterol (HDL-C) were significantly increased (HRs (95% CI) were 1.48 (1.11 to 1.96), 1.92 (1.49 to 2.46) and 1.67 (1.35 to 2.07), respectively). The AUCs of non-HDL-C (0.685, 95% CI 0.659 to 0.711), triglyceride (TG) (0.684, 95% CI 0.658 to 0.710), total cholesterol (TC)/HDL-C (0.685, 95% CI 0.659 to 0.712) and TG/HDL-C (0.680, 95% CI 0.654 to 0.706) were significantly (p<0.005) larger than that of other lipid parameters.

CONCLUSION: Middle-aged and elderly adults with hypertriglyceridaemia, hypercholesterolaemia and low HDL-C were at higher risk for developing diabetes. Non-HDL-C, TG, TC/HDL and TG/HDL have greater performance than other lipid parameters in predicting T2DM incidence.

PMID:34035089 | DOI:10.1136/bmjopen-2020-042821

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Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial

BMJ Open. 2021 May 25;11(5):e045559. doi: 10.1136/bmjopen-2020-045559.

ABSTRACT

INTRODUCTION: As a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).

METHODS AND ANALYSIS: The study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.

ETHICS AND DISSEMINATION: The protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.

TRIAL REGISTRATION NUMBER: NCT03539445.

PMID:34035100 | DOI:10.1136/bmjopen-2020-045559

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Development and validation of a clinical prediction rule for development of diabetic foot ulceration: an analysis of data from five cohort studies

BMJ Open Diabetes Res Care. 2021 May;9(1):e002150. doi: 10.1136/bmjdrc-2021-002150.

ABSTRACT

INTRODUCTION: The aim of the study was to develop and validate a clinical prediction rule (CPR) for foot ulceration in people with diabetes.

RESEARCH DESIGN AND METHODS: Development of a CPR using individual participant data from four international cohort studies identified by systematic review, with validation in a fifth study. Development cohorts were from primary and secondary care foot clinics in Europe and the USA (n=8255, adults over 18 years old, with diabetes, ulcer free at recruitment). Using data from monofilament testing, presence/absence of pulses, and participant history of previous ulcer and/or amputation, we developed a simple CPR to predict who will develop a foot ulcer within 2 years of initial assessment and validated it in a fifth study (n=3324). The CPR’s performance was assessed with C-statistics, calibration slopes, calibration-in-the-large, and a net benefit analysis.

RESULTS: CPR scores of 0, 1, 2, 3, and 4 had a risk of ulcer within 2 years of 2.4% (95% CI 1.5% to 3.9%), 6.0% (95% CI 3.5% to 9.5%), 14.0% (95% CI 8.5% to 21.3%), 29.2% (95% CI 19.2% to 41.0%), and 51.1% (95% CI 37.9% to 64.1%), respectively. In the validation dataset, calibration-in-the-large was -0.374 (95% CI -0.561 to -0.187) and calibration slope 1.139 (95% CI 0.994 to 1.283). The C-statistic was 0.829 (95% CI 0.790 to 0.868). The net benefit analysis suggested that people with a CPR score of 1 or more (risk of ulceration 6.0% or more) should be referred for treatment.

CONCLUSION: The clinical prediction rule is simple, using routinely obtained data, and could help prevent foot ulcers by redirecting care to patients with scores of 1 or above. It has been validated in a community setting, and requires further validation in secondary care settings.

PMID:34035053 | DOI:10.1136/bmjdrc-2021-002150