METHODS: A total of 547 ankles from 406 patients underwent surgery for LAI between 2019 and 2022. If ligament fibers remained in US images, they were evaluated as positive. If the ligament was not visualized, it was evaluated as negative. Two observers performed repeated measurements. Arthroscopic findings were considered the "gold standard" for validity and diagnostic test accuracy purposes. The intra- and interobserver agreements and parameters for diagnostic accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of preoperative US imaging as intraoperative arthroscopic findings were used as reference standards.
RESULTS: The intraobserver agreement was substantial, with an agreement of 98.54% and a kappa coefficient of 0.76. The interobserver agreement was also substantial, with an agreement of 98.72% and a kappa coefficient of 0.75. The sensitivity, specificity, and accuracy of preoperative US imaging were 98.7%, 100%, and 98.7%, respectively. The PPV and NPV of US imaging were 100% and 61.1%, respectively. In the arthroscopic evaluation of the 7 cases in which US imaging showed false negative results, the ATFL ruptured at the fibular attachment and ran in contact with the talus.
CONCLUSION: A US examination finding of an intact ATFL is highly likely to be correct. An US examination finding of a ruptured ATFL can be false and may require arthroscopic confirmation.
METHOD: . This study included 126 patients with PTC and 80 controls. RTL in thyroid tissues was measured using quantitative (q) PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Kaplan-Meier and Cox regression were used to analyze postsurgical outcomes.
RESULT: . The RTL of patients was significantly shorter than that of controls. A short RTL was significantly correlated with an elevated risk of PTC in patients aged ≥ 55 years, female sex, classic subtype, and tumor size > 2 cm. A short RTL did not affect the overall survival of patients with PTC; however, it was associated with poor survival in patients with tumor size > 2 cm and tumor invasion.
CONCLUSION: . This unique study combines the use of RTL with various clinicopathological features of patients with PTC. In conclusion, RTL is a promising tumor marker that correlates with the clinical characteristics of patients with PTC. Specifically, RTL 2 cm and tumor invasion to predict the risk of PTC development and prognosis of the disease. This study will open new horizon in the use of molecular marker such as RTL for understanding its association with increased cancer risk in patients with different clinicopathological features.
METHODS: 96 eligible CgH participants were divided into the ergonomics modifications group (EMG; n = 24), physiotherapy group (PTG; n = 24), and ergonomics modifications combined with physiotherapy group (EPG; n = 24) and education control group (CNG; n = 24), the participants received the respective treatment for 4 weeks. Primary (CgH frequency) and secondary (CgH pain intensity, CgH disability, flexion rotation test (right and left), neck disability index and work ability) scores were measured. The effects of treatment at various intervals were analyzed with a 4 × 4 linear mixed model analysis (LMM) between treatment groups and time intervals.
RESULTS: Four weeks following training EPG group showed more significant changes in primary outcome CgH frequency; 4.6 CI 95% 3.63 to 5.56 when compare to control group. The same gradual improvement was noticed at 8 weeks 8.2 CI 95% 7.53 to 8.86 and at 6 months follow up 11.9 CI 95% 11.25 to 12.54 when compare to other groups (p = 0.001) which is statistically 52.97% improvement. Similar improvements can be seen in the secondary outcome measures such as CgH pain intensity, CgH disability, flexion rotation test (right and left), neck disability index and work ability in EPG group than the EMG, PTG, and CNG groups (p = 0.001) at 4 weeks, 8 weeks and at 6 months' follow-up.
CONCLUSION: This study observed that the workstation ergonomics and physiotherapy group experienced significantly more improvements in cervicogenic headache patients.
CLINICAL TRIAL REGISTRATION: Identifier NCT05827185.
OBJECTIVE: We aimed to assess the link between the descending aorta to left inferior pulmonary vein (Dao-LIPV) distance and the occurrence of triggers and drivers in atrial fibrillation (AF) ablation procedures.
METHODS: Drug-refractory AF patients who underwent first-time index catheter ablation from January 2010 to December 2019 were retrospectively assembled. The Dao-LIPV distance was measured from preablation pulmonary vein computed tomography. Patients were assigned to groups on the basis of the presence of LIPV triggers or drivers. Multivariate logistic regression was used to identify risk factors.
RESULTS: A total of 886 consecutive patients with drug-refractory AF were studied, and 63 (7.1%) patients were identified to have LIPV triggers or drivers. The Dao-LIPV distance had a better predictive performance (area under the curve, 0.70) compared with persistent AF (area under the curve, 0.57). Multivariate logistic regression analysis showed that Dao-LIPV distance ≤2.5 mm (odds ratio, 3.96; 95% CI, 2.15-7.29; P < .001) and persistent AF (odds ratio, 1.73; 95% CI, 1.02-2.94]; P = .044) were independent predictors for the presence of LIPV triggers or drivers. A risk score model was established to predict the probability of LIPV triggers or drivers with persistent AF (10.2%), Dao-LIPV distance ≤2.5 mm (11.4%), and both (15.0%).
CONCLUSION: The proximity of the Dao-LIPV was correlated to the presence of LIPV triggers or drivers. We developed a risk score model indicating that persistent AF and Dao-LIPV distances ≤2.5 mm significantly increase the risk of LIPV triggers or drivers, aiding electrophysiologists in preparing for and performing catheter ablation more effectively.
RESEARCH METHOD: The study has adopted a mixed-method research design. Data was collected from 15 frontline healthcare workers through semi-structured interviews to achieve study objectives. Descriptives and content analysis were conducted to explore voice barriers and alternative practices to solve their concerns. After that, a quantitative study was conducted to determine the statistical significance of the identified voice barriers and the magnitude of their effect. For this purpose, data was collected from 480 frontline healthcare workers in the primary, secondary, and territory healthcare units. A questionnaire survey was used for data collection. Then, multistage hierarchical regression analysis was employed for data analysis.
RESULTS: Study findings highlight the determinants of two key factors: withholding patient safety concerns and withholding worker safety concerns. First, the study identifies several factors that increase the likelihood of healthcare workers withholding concerns about patient safety. These factors include professional designation, work experience, blackmailing, overconfidence, longer work tenure, feelings of insult, early career stage, fear of patient reactions, bad past experiences, job insecurity, and uncooperative management. Fear of increased workload also plays a significant role. Second, when it comes to work-related safety concerns, factors such as gender, shyness, lack of confidence, fear of duty changes, management issues, interpersonal conflicts, and resource shortages contribute to the withholding of concerns. To navigate these challenges, healthcare workers often resort to strategies such as seeking political connections, personal settlements, transfers, union protests, quitting, using social media, engaging in private practice, or referring patients to other hospitals.
CONCLUSION: Findings demonstrates that healthcare workers in Pakistan often withhold safety concerns due to hierarchical pressures, personal insecurities, and fear of repercussions. Their reliance on external mechanisms, such as political influence or social media, underscores the need for significant reforms to improve safety culture and management support. Addressing these issues is crucial for ensuring both patient and worker safety.
METHODS: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10-54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values-a metric assessing gain in forecasting accuracy-by comparing predicted versus observed ASFRs from the past 15 years (2007-21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline.
FINDINGS: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63-5·06) to 2·23 (2·09-2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137-147), declining to 129 million (121-138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1-canonically considered replacement-level fertility-in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7-29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59-2·08) in 2050 and 1·59 (1·25-1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6-43·1) in 2050 and 54·3% (47·1-59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions-decreasing, for example, in south Asia from 24·8% (23·7-25·8) in 2021 to 16·7% (14·3-19·1) in 2050 and 7·1% (4·4-10·1) in 2100-but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40-1·92) in 2050 and 1·62 (1·35-1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction.
INTERPRETATION: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world.
FUNDING: Bill & Melinda Gates Foundation.
METHODS: 240 HER2-positive MBC patients from 2004 to 2015 were retrieved from the surveillance, epidemiology, and end results (SEER) database. All HER2-positive MBC patients were divided randomly into training (n = 144) and validation cohorts (n = 96) according to a ratio of 6:4. Univariate and multivariate Cox regression analyses were used to determine the prognostic factors associated with HER2-positive MBC patients. A clinical prediction model was constructed to predict the overall survival of these patients. The nomogram model was assessed by using receiver operating characteristics (ROC) curves, calibration plots and decision curve analysis (DCA).
RESULTS: The Cox regression analysis showed that T-stage, M-stage, surgery and chemotherapy were independent risk factors for the prognosis of HER2-positive MBC patients. The model could also accurately predict the Overall survival (OS) of the patients. In the training and validation cohorts, the C indexes of the OS nomograms were 0.746 (0.677-0.815) and 0.754 (0.679-0.829), respectively. Calibration curves and DCA verified the reliability and accuracy of the clinical prediction model.
CONCLUSION: In conclusion, the predictive model constructed had good clinical utility and can help the clinician to select appropriate treatment strategies for HER2-positive MBC patients.
METHODS: This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing.
FINDINGS: Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocated to the four groups in the study after trial restart on Sept 30, 2020 (nine with haemophilia A and 12 with haemophilia B in group 1; 18 with haemophilia A and 24 with haemophilia B in group 2; nine with haemophilia A in group 3; and 46 with haemophilia A and 30 with haemophilia B in group 4). The estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0·14 (95% CI 0·07-0·29; p<0·0001) for patients with haemophilia A and 0·21 (0·10-0·45; p<0·0001) for patients with haemophilia B. The most frequent adverse events in patients who received concizumab were SARS-CoV-2 infection (19 [13%] of 151 patients), an increase in fibrin D-dimers (12 [8%] patients), and upper respiratory tract infection (ten [7%] patients). There was one fatal adverse event possibly related to treatment (intra-abdominal haemorrhage in a patient from group 4 with haemophilia A with a long-standing history of hypertension). No thromboembolic events were reported between the trial restart and confirmatory analysis cutoff.
INTERPRETATION: Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors.
FUNDING: Novo Nordisk.
Methods: Sixty-four patients aged 18-60 years, American Society of Anaesthesiologists (ASA) class I-II who underwent elective surgery were randomised to a Marsh group (n= 32) or Schnider group (n= 32). All the patients received a 1 μg/kg loading dose of dexmedetomidine, followed by TCI anaesthesia with remifentanil at 2 ng/mL. After the effect-site concentration (Ce) of remifentanil reached 2 ng/mL, propofol TCI induction was started. Anaesthesia induction commenced in the Marsh group at a target plasma concentration (Cpt) of 2 μg/mL, whereas it started in the Schnider group at a target effect-site concentration (Cet) of 2 μg/mL. If induction was delayed after 3 min, the target concentration (Ct) was gradually increased to 0.5 μg/mL every 30 sec until successful induction. The Ct at successful induction, induction time, Ce at successful induction and haemodynamic parameters were recorded.
Results: The Ct for successful induction in the Schnider group was significantly lower than in the Marsh group (3.48 [0.90] versus 4.02 [0.67] μg/mL;P= 0.01). The induction time was also shorter in the Schnider group as compared with the Marsh group (134.96 [50.91] versus 161.59 [39.64]) sec;P= 0.02). There were no significant differences in haemodynamic parameters and Ce at successful induction.
Conclusion: In the between-group comparison, dexmedetomidine reduced the Ct requirement for induction and shortened the induction time in the Schnider group. The inclusion of baseline groups without dexmedetomidine in a four-arm comparison of the two models would enhance the validity of the findings.
Methods: All patients admitted into our centre were screened for eligibility and those who underwent surgery from September 2016 to September 2017 had a D-dimer screening after surgery, followed by an ultrasound Doppler if the former was positive. The choice of anticoagulant therapy was not influenced by this study, and observation of the use was in keeping with usual practices in our centre was done.
Results: A total number of 331 patients were recruited in this study, however, after the inclusion and exclusion criteria had been met, 320 patients remained eligible, i.e. suitable for analysis. The mean age of our patients was 46 years, with 66% being male patients. A majority of the cases in this study were cranial related, with only 5% being spine surgeries. On the multivariate analysis, the Well's score and the number of days in bed remained statistically significant, after adjusting for age group, gender, ethnicity, type of central venous access and type of DVT prophylaxis with an adjusted odd's ratio, and a confidence interval of 95%, and P < 0.05 for each.
Conclusion: Well's scoring and number of days in bed were independent factors affecting the rate of DVT in patients undergoing neurosurgical procedures in our centre.
Methods: We included patients with histopathologically diagnosed head and neck cancers who had received radiation, with an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and age range of 15-60 years. Patients with prior radiotherapy and chemotherapy, edentulous status, total parotidectomy, sicca syndrome or on xerosis-induced medications were excluded. We assigned 15 patients each to the Oral7® and salt-soda groups.
Results: There was no significant difference in the mean Decayed, Missing and Filling Teeth (DMFT) score between groups. Head and neck cancer patients who were on Oral7® had a significantly better quality of life than those on salt-soda in relation to the swallowing problems, social eating, mouth opening, xerostomia and illness scales. Patients who were on Oral7® had a significantly lower xerostomia score than patients on salt-soda mouthwash. Patients on Oral7® had a significantly lower mucositis score in week 5-7 compared to patients in the salt-soda group.
Conclusion: Oral7® showed advantages over salt-soda solution in relation to reducing xerostomia, easing radiation-induced mucositis, and improving quality of life, despite the non-significant difference in the dental caries assessment.
METHODS: We conducted a comprehensive search across PubMed, Embase, and Web of Science until November 10 2024, selecting studies based on pre-defined criteria that involve adults with AF and measurements of VEGF levels. The selected studies included observational and experimental designs, excluding non-English and methodologically insufficient publications. Narrative synthesis was used for summarising the results.
RESULTS: Eight studies met the inclusion criteria. The studies show a general trend of elevated VEGF levels in AF patients compared to controls, with significant heterogeneity in findings across studies. VEGF subtypes such as VEGF-A and VEGF-D demonstrated stronger associations with AF risk compared to VEGF-C. These variations point to the complex role of VEGF in AF, influencing factors like angiogenesis, endothelial function, and inflammatory responses.
CONCLUSION: VEGF is potentially a significant contributor to AF pathophysiology, with its levels reflecting disease activity. The variability observed across studies suggests a need for standardized measurement approaches and further investigation into VEGF subtypes. Future research should focus on longitudinal studies to better understand the causal relationships and the potential of VEGF as a therapeutic target and biomarker in AF management.
CLINICAL TRIAL NUMBER: Not applicable.