Category: Statistics

Postgrad Med J. 2021 Mar 10:postgradmedj-2020-139352. doi: 10.1136/postgradmedj-2020-139352. Online ahead of print.

ABSTRACT

Cardiovascular disease (CVD) is one of the leading causes of death across the world. CVD can lead to angina, heart attacks, heart failure, strokes, and eventually, death; among many other serious conditions. The early intervention with those at a higher risk of developing CVD, typically with statin treatment, leads to better health outcomes. For this reason, clinical prediction models (CPMs) have been developed to identify those at a high risk of developing CVD so that treatment can begin at an earlier stage. Currently, CPMs are built around statistical analysis of factors linked to developing CVD, such as body mass index and family history. The emerging field of machine learning (ML) in healthcare, using computer algorithms that learn from a dataset without explicit programming, has the potential to outperform the CPMs available today. ML has already shown exciting progress in the detection of skin malignancies, bone fractures and many other medical conditions. In this review, we will analyse and explain the CPMs currently in use with comparisons to their developing ML counterparts. We have found that although the newest non-ML CPMs are effective, ML-based approaches consistently outperform them. However, improvements to the literature need to be made before ML should be implemented over current CPMs.

PMID:33692158 | DOI:10.1136/postgradmedj-2020-139352

BMJ Open. 2021 Mar 10;11(3):e042934. doi: 10.1136/bmjopen-2020-042934.

ABSTRACT

OBJECTIVES: Following well-established practices in demography, this article discusses several measures based on the number of COVID-19 deaths to facilitate comparisons over time and across populations.

SETTINGS: National populations in 186 United Nations countries and territories and populations in first-level subnational administrative entities in Brazil, China, Italy, Mexico, Peru, Spain and the USA.

PARTICIPANTS: None (death statistics only).

PRIMARY AND SECONDARY OUTCOME MEASURES: An unstandardised occurrence/exposure rate comparable to the Crude Death Rate; an indirectly age-and-sex standardised rate that can be derived even when the breakdown of COVID-19 deaths by age and sex required for direct standardisation is unavailable; the reduction in life expectancy at birth corresponding to the 2020 number of COVID-19 deaths.

RESULTS: To date, the highest unstandardised rate has been in New York, at its peak exceeding the state 2017 crude death rate. Populations compare differently after standardisation: while parts of Italy, Spain and the USA have the highest unstandardised rates, parts of Mexico and Peru have the highest standardised rates. For several populations with the necessary data by age and sex for direct standardisation, we show that direct and indirect standardisation yield similar results. US life expectancy is estimated to have declined this year by more than a year (-1.26 years), far more than during the worst year of the HIV epidemic, or the worst 3 years of the opioid crisis, and to reach its lowest level since 2008. Substantially larger reductions, exceeding 2 years, are estimated for Panama, Peru, and parts of Italy, Spain, the USA and especially, Mexico.

CONCLUSIONS: With lesser demand on data than direct standardisation, indirect standardisation is a valid alternative to adjust international comparisons for differences in population distribution by sex and age-groups. A number of populations have experienced reductions in 2020 life expectancies that are substantial by recent historical standards.

PMID:33692179 | DOI:10.1136/bmjopen-2020-042934

BMJ Open. 2021 Mar 10;11(3):e043887. doi: 10.1136/bmjopen-2020-043887.

ABSTRACT

INTRODUCTION: Very little is known about possible clinical sequelae that may persist after resolution of acute COVID-19. A recent longitudinal cohort from Italy including 143 patients followed up after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60-day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical intensive care unit patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. The primary aim of this study is to characterise physical and psychosocial sequelae in patients post-COVID-19 hospital discharge.

METHODS AND ANALYSIS: This is an international open-access prospective, observational multisite study. This protocol is linked with the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) and the WHO’s Clinical Characterisation Protocol, which includes patients with suspected or confirmed COVID-19 during hospitalisation. This protocol will follow-up a subset of patients with confirmed COVID-19 using standardised surveys to measure longer term physical and psychosocial sequelae. The data will be linked with the acute phase data. Statistical analyses will be undertaken to characterise groups most likely to be affected by sequelae of COVID-19. The open-access follow-up survey can be used as a data collection tool by other follow-up studies, to facilitate data harmonisation and to identify subsets of patients for further in-depth follow-up. The outcomes of this study will inform strategies to prevent long-term consequences; inform clinical management, interventional studies, rehabilitation and public health management to reduce overall morbidity; and improve long-term outcomes of COVID-19.

ETHICS AND DISSEMINATION: The protocol and survey are open access to enable low-resourced sites to join the study to facilitate global standardised, longitudinal data collection. Ethical approval has been given by sites in Colombia, Ghana, Italy, Norway, Russia, the UK and South Africa. New sites are welcome to join this collaborative study at any time. Sites interested in adopting the protocol as it is or in an adapted version are responsible for ensuring that local sponsorship and ethical approvals in place as appropriate. The tools are available on the ISARIC website (www.isaric.org). PROTOCOL REGISTRATION NUMBER: osf.io/c5rw3/ PROTOCOL VERSION: 3 August 2020 EUROQOL ID: 37035.

PMID:33692181 | DOI:10.1136/bmjopen-2020-043887

BMJ Open. 2021 Mar 10;11(3):e044239. doi: 10.1136/bmjopen-2020-044239.

ABSTRACT

OBJECTIVES: To identify patterns of age disparities in cancer survival, using colon and lung cancer as exemplars.

DESIGN: Systematic review of the literature.

DATA SOURCES: We searched Embase, MEDLINE, Scopus and Web of Science through 18 December 2020.

ELIGIBILITY CRITERIA: We retained all original articles published in English including patients with colon or lung cancer. Eligible studies were required to be population-based, report survival across several age groups (of which at least one was over the age of 65) and at least one other characteristic (eg, sex, treatment).

DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the quality of included studies against selected evaluation domains from the QUIPS tool, and items concerning statistical reporting. We evaluated age disparities using the absolute difference in survival or mortality rates between the middle-aged group and the oldest age group, or by describing survival curves.

RESULTS: Out of 3047 references, we retained 59 studies (20 for colon, 34 for lung and 5 for both sites). Regardless of the cancer site, the included studies were highly heterogeneous and often of poor quality. The magnitude of age disparities in survival varied greatly by sex, ethnicity, socioeconomic status, stage at diagnosis, cancer site, and morphology, the number of nodes examined and treatment strategy. Although results were inconsistent for most characteristics, we consistently observed greater age disparities for women with lung cancer compared with men. Also, age disparities increased with more advanced stages for colon cancer and decreased with more advanced stages for lung cancer.

CONCLUSIONS: Although age is one of the most important prognostic factors in cancer survival, age disparities in colon and lung cancer survival have so far been understudied in population-based research. Further studies are needed to better understand age disparities in colon and lung cancer survival.

PROSPERO REGISTRATION NUMBER: CRD42020151402.

PMID:33692182 | DOI:10.1136/bmjopen-2020-044239

Sci Adv. 2021 Mar 10;7(11):eabe4270. doi: 10.1126/sciadv.abe4270. Print 2021 Mar.

ABSTRACT

It is a long-standing goal to create light with unique quantum properties such as squeezing and entanglement. We propose the generation of quantum light using free-electron interactions, going beyond their already ubiquitous use in generating classical light. This concept is motivated by developments in electron microscopy, which recently demonstrated quantum free-electron interactions with light in photonic cavities. Such electron microscopes provide platforms for shaping quantum states of light through a judicious choice of the input light and electron states. Specifically, we show how electron energy combs implement photon displacement operations, creating displaced-Fock and displaced-squeezed states. We develop the theory for consecutive electron-cavity interactions with a common cavity and show how to generate any target Fock state. Looking forward, exploiting the degrees of freedom of electrons, light, and their interaction may achieve complete control over the quantum state of the generated light, leading to novel light statistics and correlations.

PMID:33692108 | DOI:10.1126/sciadv.abe4270

BMJ Support Palliat Care. 2021 Mar 10:bmjspcare-2020-002801. doi: 10.1136/bmjspcare-2020-002801. Online ahead of print.

ABSTRACT

BACKGROUND: Cholestatic itch is caused by intrahepatic liver diseases, such as primary biliary cirrhosis and extrahepatic obstruction of the biliary tree, often caused by tumours. The pathophysiology of cholestatic itch is complex and no single treatment has proved definitive. Naltrexone is an opioid receptor antagonist, which reduces central opioidergic tone, believed to be raised in patients with cholestatic pruritus.

AIM: To review and assess the efficacy of oral naltrexone for the treatment of cholestatic itch.

METHODS: Search of electronic databases, grey literature, clinical trials registries and handsearching for studies including naltrexone for cholestatic itch. Full papers were obtained if relevant and studies graded.

RESULTS: Thirteen papers were included in the analysis, including three randomised controlled trials, one controlled clinical trial, one open-label pilot study, seven case reports and one retrospective notes review. All studies found naltrexone to be effective in relieving pruritus. In all five studies performing statistical analysis, naltrexone significantly reduced pruritus compared with baseline. 37% of patients reported side effects, notably opioid withdrawal-type reactions and recurrence of previous pain, from all pathologies.

CONCLUSIONS: Oral naltrexone therapy helps relieve cholestatic itch and although it should be used with caution in patients using exogenous opioids for analgesia, it should be considered when treating refractory pruritus in patients with end-stage liver disease.

PMID:33692114 | DOI:10.1136/bmjspcare-2020-002801

Postgrad Med J. 2021 Mar 10:postgradmedj-2021-139748. doi: 10.1136/postgradmedj-2021-139748. Online ahead of print.

ABSTRACT

Medical schools in the UK typically use prior academic attainment and an admissions test (University Clinical Aptitude Test (UCAT), Biomedical Admissions Test (BMAT) or the Graduate Medical School Admissions Test (GAMSAT)) to help select applicants for interview. To justify their use, more information is needed about the predictive validity of these tests. Thus, we investigated the relationship between performance in admissions tests and the Membership of the Royal College of Surgeons (MRCS) examination.The UKMED database (https://www.ukmed.ac.uk) was used to access medical school selection data for all UK graduates who attempted MRCS Part A (n=11 570) and Part B (n=5690) between 2007 and 2019. Univariate and multivariate logistic regression models identified independent predictors of MRCS success. Pearson correlation coefficients examined the linear relationship between test scores and MRCS performance.Successful MRCS Part A candidates scored higher in A-Levels, UCAT, BMAT and GAMSAT (p<0.05). No significant differences were observed for MRCS Part B. All admissions tests were found to independently predict MRCS Part A performance after adjusting for prior academic attainment (A-Level performance) (p<0.05). Admission test scores demonstrated statistically significant correlations with MRCS Part A performance (p<0.001).The utility of admissions tests is clear with respect to helping medical schools select from large numbers of applicants for a limited number of places. Additionally, these tests appear to offer incremental value above A-Level performance alone. We expect this data to guide medical schools’ use of admissions test scores in their selection process.

PMID:33692157 | DOI:10.1136/postgradmedj-2021-139748

BMJ. 2021 Mar 10;372:n436. doi: 10.1136/bmj.n436.

ABSTRACT

Severe covid-19 pneumonia has posed critical challenges for the research and medical communities. Older age, male sex, and comorbidities increase the risk for severe disease. For people hospitalized with covid-19, 15-30% will go on to develop covid-19 associated acute respiratory distress syndrome (CARDS). Autopsy studies of patients who died of severe SARS CoV-2 infection reveal presence of diffuse alveolar damage consistent with ARDS but with a higher thrombus burden in pulmonary capillaries. When used appropriately, high flow nasal cannula (HFNC) may allow CARDS patients to avoid intubation, and does not increase risk for disease transmission. During invasive mechanical ventilation, low tidal volume ventilation and positive end expiratory pressure (PEEP) titration to optimize oxygenation are recommended. Dexamethasone treatment improves mortality for the treatment of severe and critical covid-19, while remdesivir may have modest benefit in time to recovery in patients with severe disease but shows no statistically significant benefit in mortality or other clinical outcomes. Covid-19 survivors, especially patients with ARDS, are at high risk for long term physical and mental impairments, and an interdisciplinary approach is essential for critical illness recovery.

PMID:33692022 | DOI:10.1136/bmj.n436

Br J Sports Med. 2021 Mar 10:bjsports-2020-102606. doi: 10.1136/bjsports-2020-102606. Online ahead of print.

ABSTRACT

OBJECTIVE: We assessed past-season, pre-season and in-season risk factors to investigate their association with an in-season groin problem in male amateur football players.

METHODS: Past-season groin-pain information and pre-season short-lever and long-lever adductor squeeze strength were obtained at baseline, together with anthropometrics (weight, lower limb lever length) and player age. In-season hip-related and groin-related sporting function was monitored every 4 weeks using the Sports and Recreation (Sport) subscale from the Hip And Groin Outcome Score questionnaire (HAGOS (Sport)). Groin problems, including time-loss groin injuries and groin pain irrespective of time loss, were collected over a 39-week competitive in-season. We estimated relative risk (RR), and 95% credibility interval (ICr) from logistic regressions fitted in a Bayesian framework.

RESULTS: Players (n=245) suffering from groin pain during the past-season had 2.4 times higher risk of experiencing a groin problem in the new season (2.40 RR; 95% ICr 1.5 to 3.7). This risk was reduced by 35% (0.65 RR; 95% ICr 0.42 to 0.99) per unit (N·m/kg) increase in the long-lever adductor squeeze test. Player age, short-lever squeeze test and the HAGOS (Sport) scores were not associated with the risk of a groin problem.

CONCLUSIONS: Past-season groin pain increased the risk of a groin problem in the new in-season. This risk was reduced by higher pre-season long-lever adductor squeeze strength. Past-season groin-pain information and long-lever adductor squeeze strength can be quickly obtained during pre-season to identify players with an elevated risk of in-season groin problems. This may be key to reduce these problems in the new season.

PMID:33692032 | DOI:10.1136/bjsports-2020-102606

Sci Adv. 2021 Mar 10;7(11):eabd1239. doi: 10.1126/sciadv.abd1239. Print 2021 Mar.

ABSTRACT

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.

PMID:33692100 | DOI:10.1126/sciadv.abd1239