Polyclonal hypergammaglobulinaemia: towards definition of a threshold.

BACKGROUND: Polyclonal hypergammaglobulinaemia (PH) represents a classic diagnosis problem in internal medicine. However, there is no consensus threshold for PH. The aim of this study was to define a threshold for PH. METHODS: We conducted a retrospective multicentric study using laboratory biological databases between 1 January 2016 and 31 December 2016 in two university hospitals and one non-university hospital. All patients 18 years old or over and with at least one serum protein electrophoresis (SPE) available in 2016 were included. Exclusion criteria were monoclonal, biclonal, or oligoclonal spikes or, in case of hypogammaglobulinaemia, proven free light chain gammopathy. The main endpoint was to define the threshold values for PH in this population. Another objective was to define the 95th percentile of the distribution. RESULTS: 20 766 SPEs were included in this cohort. The PH threshold on 95th percentile was 18.9 g/L. The threshold varied according to geographical areas. CONCLUSIONS: This is the first study to scientifically define a PH threshold. The main limitation is that our threshold is only biological. The study was not designed to associate this threshold with a clinically active disease. In conclusion, while the 19 g/L cut-off seems the most relevant threshold, but it will need to be validated by prospective studies.

Polyclonal hypergammaglobulinaemia: towards definition of a threshold.

BACKGROUND: Polyclonal hypergammaglobulinaemia (PH) represents a classic diagnosis problem in internal medicine. However, there is no consensus threshold for PH. The aim of this study was to define a threshold for PH. METHODS: We conducted a retrospective multicentric study using laboratory biological databases between 1 January 2016 and 31 December 2016 in two university hospitals and one non-university hospital. All patients 18 years old or over and with at least one serum protein electrophoresis (SPE) available in 2016 were included. Exclusion criteria were monoclonal, biclonal, or oligoclonal spikes or, in case of hypogammaglobulinaemia, proven free light chain gammopathy. The main endpoint was to define the threshold values for PH in this population. Another objective was to define the 95th percentile of the distribution. RESULTS: 20 766 SPEs were included in this cohort. The PH threshold on 95th percentile was 18.9 g/L. The threshold varied according to geographical areas. CONCLUSIONS: This is the first study to scientifically define a PH threshold. The main limitation is that our threshold is only biological. The study was not designed to associate this threshold with a clinically active disease. In conclusion, while the 19 g/L cut-off seems the most relevant threshold, but it will need to be validated by prospective studies.

Prognostic and clinicopathological value of Ki-67 in patients with oesophageal squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVES: The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was performed to identify the precise value of Ki-67 in predicting the prognosis of ESCC. DESIGN: The current meta-analysis was carried out in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. DATA SOURCES: Electronic databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched until 26 September 2023. STATISTICAL METHODS: Pooled HRs and corresponding 95% CIs were calculated to estimate the role of Ki-67 in predicting overall survival (OS) and disease-free survival (DFS) in ESCC. Between-study heterogeneity was evaluated using Cochrane's Q test and I2 statistics. Specifically, significant heterogeneities were identified based on p<0.10 on the Q statistic test or I2>50% so the random-effects model should be used; otherwise, the fixed-effects model should be used. The relationship between Ki-67 and clinicopathological characteristics of ESCC was evaluated by combining ORs with their corresponding 95% CIs. RESULTS: 11 articles with 1124 patients were included in the present meta-analysis. Based on our analysis, increased Ki-67 expression was markedly associated with poor OS (HR 1.62, 95% CI 1.15 to 2.28, p=0.006) and DFS (HR 1.72, 95% CI 1.22 to 2.43, p=0.002) in ESCC. Moreover, subgroup analysis revealed that Ki-67 upregulation significantly predicted OS and DFS when a Ki-67 threshold of >30% was used. Nonetheless, Ki-67 was not significantly associated with sex, T stage, N stage, TNM stage, tumour differentiation or tumour location. CONCLUSIONS: In the present meta-analysis, high Ki-67 expression significantly predicted OS and DFS in patients with ESCC, especially when Ki-67>30% was used as the threshold. These results suggest that Ki-67 could serve as an effective and reliable prognostic indicator for ESCC.

EditorialAssignment.

INTRODUCTION: Primary membranous nephropathy (PMN) is a major cause of nephrotic syndrome in adults. Rituximab has been recommended in the treatment of PMN by the updated Kidney Disease Improved Outcome guideline. However, the optimal dosing regimen of rituximab for the initial treatment of patients with PMN is unclear. METHODS AND ANALYSIS: A comprehensive screening will be performed by searching PubMed, Embase and the CENTRAL (Cochrane Central Register of Controlled Trials) without language restriction. Studies evaluating the efficacy of rituximab monotherapy using the following types of dosing regimens will be included: high-dose regimen; standard regimen and low-dose regimen. Studies with less than 10 participants will be excluded. The primary outcome is the remission rate at 12 months. The secondary outcomes are remission rate at 6 and 24 months, complete remission rate at 6, 12 and 24 months, relapse at 6, 12 and 24 months, and side effects. Risk of Bias In Non-randomised Studies of Interventions tool will be used to assess the risk of bias for non-randomised studies and the Cochrane risk of bias assessment tool will be used for randomised controlled trials. The pooled remission rate, complete remission rate, relapse rate and side effects will be estimated using the metaprop command. All analyses will be calculated using Stata software (V.15.0; StataCorp). ETHICS AND DISSEMINATION: Ethics approval is not required. The results of our study will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42022319401.

Adherence to preventive behaviours and associated factors towards COVID-19 among adults in Gurage zone, Ethiopia, 2020: a community-based cross-sectional study.

OBJECTIVES: People's adherence to preventive practices for COVID-19 is fundamental to controlling the transmission of the virus. Therefore, this study is aimed at assessing adherence to preventive practices for COVID-19 and associated factors among the general population in Gurage zone, Ethiopia. METHODS: A community-based cross-sectional study was conducted to assess preventive practices and associated factors for COVID-19 among adults in the Gurage zone. The study is based on health belief model constructs. The study involved 398 participants. A multistage sampling technique was employed to recruit study participants. An interviewer-administered, close-ended, structured questionnaire was used to collect data. Binary and multivariable logistic regressions were used to identify independent predictors of the outcome variable. RESULTS: The overall adherence to all recommended preventive behaviours of COVID-19 was 17.7%. The majority of respondents (73.1%) practice at least one of the recommended preventive behaviours for COVID-19. Among adults' COVID-19 preventive behaviours score, wearing a face mask was the highest (82.3%) and social distancing was the lowest (35.4%). Residence adjusted OR (AOR)) 3.42 (95% CI 1.6 to 7.31), marital status AOR 0.33 (95% CI (0.15 to 0.71)), knowledge of the absence/presence of the COVID-19 vaccine AOR 0.45 (95% CI (0.21 to 0.95)) and self-rated level of knowledge as poor AOR 0.052 (95% CI 0.036 to 0.18) and self-rated level of knowledge as not bad AOR 0.14 (95% CI 0.09 to 0.82) were significantly associated with social distancing practice. Factors affecting other COVID-19 preventive behaviours are described in the 'Results' section. CONCLUSION: Prevalence of good adherence to recommended preventive behaviours for COVID-19 was very low. Residence, marital status, knowledge of vaccine presence, knowledge of curative drug presence, knowledge of the incubation period, the self-rated level of knowledge and perceived risk to be infected with COVID-19 are significantly associated factors with adherence to preventive behaviours.

Evaluating an audit and feedback intervention for reducing overuse of pathology test requesting by Australian general practitioners: protocol for a factorial cluster randomised controlled trial.

INTRODUCTION: Consistent evidence shows pathology services are overused worldwide and that about one-third of testing is unnecessary. Audit and feedback (AF) is effective for improving care but few trials evaluating AF to reduce pathology test requesting in primary care have been conducted. The aim of this trial is to estimate the effectiveness of AF for reducing requests for commonly overused pathology test combinations by high-requesting Australian general practitioners (GPs) compared with no intervention control. A secondary aim is to evaluate which forms of AF are most effective. METHODS AND ANALYSIS: This is a factorial cluster randomised trial conducted in Australian general practice. It uses routinely collected Medicare Benefits Schedule data to identify the study population, apply eligibility criteria, generate the interventions and analyse outcomes. On 12 May 2022, all eligible GPs were simultaneously randomised to either no intervention control or to one of eight intervention groups. GPs allocated to an intervention group received individualised AF on their rate of requesting of pathology test combinations compared with their GP peers. Three separate elements of the AF intervention will be evaluated when outcome data become available on 11 August 2023: (1) invitation to participate in continuing professional development-accredited education on appropriate pathology requesting, (2) provision of cost information on pathology test combinations and (3) format of feedback. The primary outcome is the overall rate of requesting of any of the displayed combinations of pathology tests of GPs over 6 months following intervention delivery. With 3371 clusters, assuming no interaction and similar effects for each intervention, we anticipate over 95% power to detect a difference of 4.4 requests in the mean rate of pathology test combination requests between the control and intervention groups. ETHICS AND DISSEMINATION: Ethics approval was received from the Bond University Human Research Ethics Committee (#JH03507; approved 30 November 2021). The results of this study will be published in a peer-reviewed journal and presented at conferences. Reporting will adhere to Consolidated Standards of Reporting Trials. TRIAL REGISTRATION NUMBER: ACTRN12622000566730.

Potential key roles of tumour budding: a representative malignant pathological feature of non-small cell lung cancer and a sensitive indicator of prognosis.

OBJECTIVES: To investigate the relationship between tumour budding, clinicopathological characteristics of patients and prognosis in non-small cell lung cancer. STUDY DESIGN: A retrospective study was used. PARTICIPANTS: We selected 532 patients with non-small cell lung cancer from China, including 380 patients with adenocarcinoma and 152 with squamous cell carcinoma. PRIMARY AND SECONDARY OUTCOME MEASURES: Tumour budding was visible using H&E staining as well as pancytokeratin staining. The count data and measurement data were compared using the χ2 test and the t-test, respectively. The overall survival rate was the follow-up result. The survival curves were drawn using the Kaplan-Meier method, and the differences between groups were analysed using the log-rank method. The independent prognostic factor of patients with lung cancer was determined using a multivariate Cox proportional hazard model. RESULTS: In patients with lung adenocarcinoma, there was a correlation between tumour budding and spread through air spaces (OR 36.698; 95% CI 13.925 to 96.715; p<0.001), and in patients with squamous cell carcinoma, tumour budding state was closely related to the peritumoural space (OR 11.667; 95% CI 4.041 to 33.683; p<0.001). On Cox regression analysis, multivariate analysis showed that tumour budding, pleural and vascular invasion, spread through air spaces, tumour size, lymph node metastasis, and tumour node metastasis stage were independent risk factors of prognosis for patients with non-small cell lung cancer. CONCLUSIONS: As an effective and simple pathological diagnostic index, it is necessary to establish an effective grading system in the clinical diagnosis of lung cancer to verify the value of tumour budding as a prognostic indicator. We hope that this analysis of Chinese patients with non-small cell lung cancer can provide useful reference material for the continued study of tumour budding.

Microscopic and macroscopic comparisons of 0.223 soft point and full metal jacket ammunition with bos taurus scapulae as a proxy to human flat bones.

BACKGROUND: The prevalence of civilian 0.223 ammunition is widespread. Due to low costs and the same dimensions as a 5.56×45 mm North Atlantic Treaty Organization, this round is exceptionally popular. However, recent mass shootings have employed soft point (SP) expanding ammunition to cause grievous wounds compared with military full metal jacket (FMJ) rounds that do not rapidly expand on impact. METHODS: The aim of this given study is to compare FMJ and SP rounds to determine if there are diagnostic differences between the bullet types in the wounds inflicted to flat bones. Bos taurus scapulae were used for 25 m simulated cranial gunshot injuries. Scanning electron microscopy was employed to assess the difference in wound morphology and elemental analysis between SP and FMJ rounds. RESULTS: Entrance and exit wound morphology change significantly between the two different types of ammunition as seen with circumferential delamination which is indicative of FMJ rounds and is not seen with the softer SP hunting rounds. Lead staining of the entrance wound is visible on only the SP rounds. CONCLUSION: Gunshot flat bone wound morphology is distinctively different between SP and FMJ rounds. Circumferential delamination is only seen with FMJ due to the hardness of the round. Lead staining is only seen with SP rounds due to bullet composition.

Urinary incontinence and sedentary behaviour in nursing home residents in Osona, Catalonia: protocol for the OsoNaH project, a multicentre observational study.

INTRODUCTION: Several studies have shown that physical activity (PA) levels and sedentary behaviour (SB) are independent risk factors for many health-related issues. However, there is scarce evidence supporting the relationship between SB and urinary incontinence (UI) in community-dwelling older adults, and no information on any possible association in institutionalised older adults. Stage I of this project has the main objective of determining the prevalence of UI and its associated factors in nursing home (NH) residents, as well as analysing the association between UI (and its types) and SB. Stage II aims to investigate the incidence and predictive factors of functional and continence decline, falls, hospitalisations, mortality and the impact of the COVID-19 pandemic among NH residents. METHODS AND ANALYSIS: Stage I is an observational, multicentre, cross-sectional study with mixed methodology that aims to explore the current status of several health-related outcomes in NH residents of Osona (Barcelona, Spain). The prevalence ratio will be used as an association measure and multivariate analysis will be undertaken using Poisson regression with robust variance. Stage II is a 2-year longitudinal study that aims to analyse functional and continence decline, incidence of falls, hospitalisations, mortality and the impact of the COVID-19 pandemic on these outcomes. A survival analysis using the actuarial method for functional decline and continence, evaluated every 6 months, and the Kaplan-Meier method for falls, hospitalisations and deaths, and Cox regression for multivariate analysis will be undertaken. ETHICS AND DISSEMINATION: The study received the following approvals: University of Vic - Central University of Catalonia Ethics and Research Committee (92/2019 and 109/2020), Clinical Research Ethics Committee of the Osona Foundation for Health Research and Education (FORES) (code 2020118/PR249). Study results will be disseminated at conferences, meetings and through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04297904.

Translational deep phenotyping of deaths related to the COVID-19 pandemic: protocol for a prospective observational autopsy study.

INTRODUCTION: The COVID-19 pandemic is an international emergency with an extreme socioeconomic impact and a high mortality and disease burden. The COVID-19 outbreak is neither fully understood nor fully pictured. Autopsy studies can help understand the pathogenesis of COVID-19 and has already resulted in better treatment of patients. Structured and systematic autopsy of COVID-19-related deaths will enhance the mapping of pathophysiological pathways, not possible in the living. Furthermore, it provides an opportunity to envision factors translationally for the purpose of disease prevention in this and future pandemics. This is the protocol for an autopsy study that offers an umbrella for deep and diverse investigations of COVID-19-related deaths, including a systematic investigation of 'long' COVID-19 by means of extensive and systematic tissue sampling. METHODS AND ANALYSIS: A COVID-19-specific autopsy algorithm has been created to cover all cases undergoing clinical or forensic autopsy in Denmark. The algorithm describes advanced tissue sampling and a translational analytical follow-up for deep phenotyping. The translational approach covers registry data, postmortem imaging, gross autopsy findings, microscopic organ changes, postmortem toxicology, postmortem biochemical investigation, microbiological profiling and immunological status at the time of death, and future research projects covering genetics and epigenetics on an organ level. ETHICS AND DISSEMINATION: This study has been approved by the Regional Ethics Committee of the Region of Greater Copenhagen (No: H-20078436) and the Danish Data Protection Agency (No: 2002-54-1080). Next of kin gave informed consent to research. The study results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: This study is purely observational and, as such, does not meet the criteria of the International Committee of Medical Journal Editors for clinical trials; thus, there is no need for registration in a database of research trials, such as clinical trials. To facilitate cooperation in research, provide transparency on case recruitment for publications to come and to avoid unnecessary duplicate work, we nevertheless wish to publish our protocol.

International psychometric validation of the Living with Chronic Illness Scale in Spanish-speaking patients with chronic obstructive pulmonary disease.

OBJECTIVES: To validate the Living with Chronic Illness (LW-CI) Scale in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Observational, cross-sectional validation study with retest. Acceptability, reliability, precision and construct validity were tested. SETTING: The study took place in primary and secondary specialised units of public and private hospitals of Spain and Colombia. PARTICIPANTS: The study included 612 patients with COPD assessed from May 2018 to May 2019. A consecutive cases sampling was done. Inclusion criteria included: (A) patients with a diagnosis of COPD; (B) native Spanish speaking; (C) able to read and understand questionnaires; and (D) able to provide informed consent. Exclusion criteria included: (A) cognitive deterioration and (B) pharmacological effect or disorder that could disrupt the assessment. RESULTS: The LW-CI-COPD presented satisfactory data quality, with no missing data or floor/ceiling effects, showing high internal consistency for all the domains (Cronbach's alpha for the total score 0.92). Test-retest reliability was satisfactory (intraclass correlation coefficient=0.92). The LW-CI-COPD correlated 0.52-0.64 with quality of life and social support measures. The scale demonstrated satisfactory known-groups validity, yielding significantly different scores in patients grouped according to COPD severity levels. CONCLUSIONS: This has been the first validation study of the LW-CI-COPD. It is a feasible, reliable, valid and precise self-reported scale to measure living with COPD in the Spanish-speaking population. Therefore, it could be recommended for research and clinical practice to measure this concept and evaluate the impact of centred-care interdisciplinary interventions based on the patients' perspective, focused on providing holistic and comprehensive care to patients with COPD.

Feasibility and acceptability study on the use of a smartphone application to facilitate balance training in the ageing population.

OBJECTIVES: This study aims to investigate the feasibility and acceptability of using an app-based technology to train balance in the older population. DESIGN: Prospective feasibility study. SETTING: The study was conducted in a university setting and participants' homes. PARTICIPANTS: Thirty-five volunteers ≥55 years old were recruited. INTERVENTION: Participants were asked to follow a balance exercise programme 7 days a week for 3 weeks using a phone application. Seventeen participants trained for a further 3 weeks. OUTCOME MEASURES: Postural sway measures during quiet standing with feet at shoulder width apart and feet together, one leg standing and tandem stance were measured at baseline, and at the end of the 3 and 6 training weeks; the International Physical Activity Questionnaire (IPAQ) assessed participants' physical activity level before training; and app acceptability was recorded using a user experience questionnaire. RESULTS: Participants on the 3 and 6-week programme on average completed 20 (±5) and 38 (±11) days of training, respectively, and all scored moderate to high on the IPAQ. Between baseline and the 3-week assessments, statistically significant improvements were observed for anteroposterior sway, mediolateral sway, sway area during tandem stance, for anteroposterior sway during one leg standing and for sway area during feet together stance. Improvements were observed at 6 week compared with baseline but those between 3 and 6 weeks were not significant. Based on the questionnaire, participants reported that the app is an appropriate tool for balance training (77%), they reported benefits from the training (50%) and found it easy to fit it into daily routine (88%). CONCLUSION: The high level of adherence and improvements observed in the analysed measures demonstrate the feasibility of using an app to train balance in moderately to highly physically active older participants. This demonstrates that given appropriate tools the older population is positive towards and receptive of digital interventions aimed to improve balance.