Category: Statistics

Int J Spine Surg. 2024 Jun 26:8609. doi: 10.14444/8609. Online ahead of print.

ABSTRACT

BACKGROUND: Progenitor cells derived from intervertebral disc tissue demonstrated immunomodulatory and regenerative properties in preclinical studies. We report the safety and efficacy results of a US Food and Drug Administration-approved clinical trial of these cells for the treatment of symptomatic degenerative disc disease.

METHODS: Sixty patients with symptomatic single-level lumbar degenerative disc disease (mean age 37.9 years, 60% men) were enrolled in a randomized, double-blinded, placebo-controlled Phase I/Phase II study at 13 clinical sites. They were randomized to receive single intradiscal injections of either low-dose cells (N = 20), high-dose cells (N = 20), vehicle alone (N = 10), or placebo (N = 10). The primary endpoint was mean visual analog scale (VAS) pain improvement >30% at 52 weeks. Disc volume was radiologically assessed. Adverse events (AEs), regardless of whether they were related to treatment, were reported. Patients were assessed at baseline and at 4, 12, 26, 52, 78, and 104 weeks posttreatment.

RESULTS: At week 52, the high-dose group had a mean VAS percentage decrease from baseline (-62.8%, P = 0.0005), achieving the endpoint of back pain improvement >30%; the mean change was also significantly greater than the minimal clinically important difference of a 20-point decrease (-42.8, P = 0.001). This clinical improvement was maintained at week 104. The vehicle group had a smaller significant decrease in VAS (-52.8%, P = 0.044), while the low-dose and placebo groups showed nonsignificant improvements. Only the high-dose group had a significant change in disc volume, with mean increases of 249.0 mm³ (P = 0.028) at 52 weeks and 402.1 mm³ (P = 0.028) at 104 weeks. A minority of patients (18.3%) reported AEs that were severe. Overall, 6.7% of patients experienced serious AEs, all in the vehicle (n = 1) or placebo (n = 3) groups, none treatment related.

CONCLUSIONS: High-dose allogeneic disc progenitor cells produced statistically significant, clinically meaningful improvements in back pain and disc volume at 1 year following a single intradiscal injection and were safe and well tolerated. These improvements were maintained at 2 years post-injection.

CLINICAL TRIAL REGISTRATION: NCT03347708-Study to Evaluate the Safety and Preliminary Efficacy of Injectable Disc Cell Therapy, a Treatment for Symptomatic Lumbar Intervertebral Disc Degeneration.

PMID:38925869 | DOI:10.14444/8609

Can J Surg. 2024 Jun 26;67(3):E252-E260. doi: 10.1503/cjs.003723. Print 2024 May-Jun.

ABSTRACT

BACKGROUND: Prescription opioid use places a considerable economic burden on health care systems. Older patients undergoing surgical procedures for painful conditions commonly receive opioids pre- and postoperatively, and are susceptible to adverse reactions. This study explores predictors of prolonged postoperative opioid use among older patients after lumbar spine surgery and the consequences in terms of health care utilization and costs.

METHODS: We conducted a retrospective population-based cohort study using Ontario administrative data from older adults undergoing spine surgery between 2006 and 2017. Data were analyzed from 90 days preoperatively to 1 year after hospital discharge, with last postoperative opioid prescriptions stratified into 90-day increments. We used multivariable ordinal logistic regression to identify predictors of long-term opioid use and generalized linear modelling to examine resource utilization and health care costs (2021 Canadian dollars).

RESULTS: Of 15 109 patients included, 40.8% received preoperative opioid prescriptions. Preoperative opioid use strongly predicted prolonged postoperative use (odds ratio [OR] 4.47, 95% confidence interval [CI] 4.16-4.79), with 48.3% of patients who received preoperative opioids continuing to use opioids for longer than 9 months, relative to 12.7% of those without preoperative use. Several other risk factors for prolonged use were identified. Patients receiving long-term postoperative opioids incurred greater health care costs relative to those with opioids prescribed for fewer than 90 days (OR 1.49, 95% CI 1.44-1.54).

CONCLUSION: Among older adults undergoing spine surgery, preoperative opioid use was a strong predictor of prolonged postoperative use, which was associated with increased health care costs. These results form an important baseline for future studies evaluating strategies to reduce opioid use targeting older surgical populations.

PMID:38925858 | DOI:10.1503/cjs.003723

Can J Surg. 2024 Jun 26;67(3):E261-E268. doi: 10.1503/cjs.002424. Print 2024 May-Jun.

ABSTRACT

BACKGROUND: Understanding patterns of peripheral nerve injuries (PNIs) and brachial plexus injuries (BPIs) is essential to preventing and appropriately managing nerve injuries. We sought to assess the incidence, cause, and severity of PNIs and BPIs sustained by patients with trauma.

METHODS: We conducted a retrospective review of the Trauma Registry Database (January 2002 to December 2020) to identify patients with PNIs or BPIs.

RESULTS: We evaluated data from 24 905 patients with trauma; 335 (1.3%) sustained PNIs (81% male; mean age 36 yr, standard deviation [SD] 16 yr) and 64 (0.3%) sustained BPIs (84% male; mean age 35, SD 15 yr). Nerves in the upper extremities were more commonly affected than those in the lower extremities. Sharp injuries (39.4%) and motorcycle accidents (32.8%) were the most frequent causes of PNIs and BPIs, respectively. Other common causes of PNI were motor vehicle collisions (16.7%) and gunshot wounds (12.8%). Many patients with PNIs (69.0%) and BPIs (53%) underwent operative management. The most frequent reconstruction for PNI was primary nerve repair (66%), while nerve transfers (48%) were more frequently used for BPI.

CONCLUSION: Nerve injuries in the trauma population have decreased over the last 3 decades with shifts in mechanisms of injury and use of imaging, electrodiagnostic tests, and surgery. Nerve injuries are often complex and time-sensitive to treat; understanding changes in trends is important to ensure optimal patient management.

PMID:38925857 | DOI:10.1503/cjs.002424

Anticancer Res. 2024 Jul;44(7):3051-3058. doi: 10.21873/anticanres.17118.

ABSTRACT

BACKGROUND/AIM: The activity and expression of matrix metalloproteinase-7 (MMP7) have been found to be upregulated in the late stages of endometriosis. However, the contribution of MMP7 genotype to endometriosis has seldom been examined. This study aimed to investigate the role of MMP7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes in determining personal susceptibility to endometriosis in a Taiwanese cohort.

PATIENTS AND METHODS: In this hospital-based case-control study, MMP7 genotypes were analyzed in 153 endometriosis and 636 individuals without endometriosis using typical polymerase chain reaction-restriction fragment length polymorphism methodology.

RESULTS: The statistical analysis revealed that MMP7 rs11568818 genotypes were differentially distributed between the endometriosis and control groups (p for trend=0.0048). Specifically, the MMP7 rs11568818 homozygous variant GG was associated with endometriosis risk compared to the wild-type AA genotype (OR=4.59, 95% CI=1.46-14.48, p=0.0136). However, the MMP7 rs11568818 heterozygous variant AG was not associated with endometriosis risk (OR=1.57, 95% CI=0.97-2.53, p=0.0854). The frequency of than variant allele G of MMP7 rs11568818 was 12.7% in the endometriosis group, significantly higher than the 7.2% observed in the control group (OR=1.90, 95% CI=1.27-2.82, p=0.0021).

CONCLUSION: MMP7 rs11568818 GG genotype was found to be a novel marker for endometriosis risk in Taiwanese.

PMID:38925847 | DOI:10.21873/anticanres.17118

Anticancer Res. 2024 Jul;44(7):3193-3198. doi: 10.21873/anticanres.17134.

ABSTRACT

BACKGROUND/AIM: Breast cancer treatment may interfere with work ability. Previous return-to-work studies have often focused on participants who were invited to participate after treatment completion. Participation varied, resulting in potential selection bias. This is a health-record-based study evaluating data completeness, both at baseline and one year after diagnosis. Correlations between baseline variables and return to work were also analyzed.

PATIENTS AND METHODS: This is a retrospective review of 150 relapse-free survivors treated in Nordland county between 2019 and 2022 (all-comers managed with different types of systemic treatment and surgery). Work status was assessed in the regional electronic patient record (EPR). A 65-years age cut-off was employed to define two subgroups.

RESULTS: At diagnosis, occupational status was assessable in all 150 patients. Almost all patients older than 65 years of age were retired (79%) or on disability pension for previously diagnosed conditions (19%). Data completeness one year after diagnosis was imperfect, because the EPR did not contain required information in 19 survivors. The majority of those ≤65 years of age at diagnosis returned to work. Only 14 of 88 patients (16%) did not return to work. Postoperative nodal stage was the only significant predictive factor. Those with pN1-3 had a lower return rate (68%) than their counterparts with lower nodal stage.

CONCLUSION: This pilot study highlights the utility and limitations of EPR-based research in a rural Norwegian setting, emphasizing the need for comprehensive, individualized interventions to support breast cancer survivors in returning to work. The findings underscore the importance of considering diverse sociodemographic and clinical factors, as well as the potential benefits of long-term, population-based studies to address these complex challenges.

PMID:38925818 | DOI:10.21873/anticanres.17134

BMJ. 2024 Jun 26;385:e078523. doi: 10.1136/bmj-2023-078523.

ABSTRACT

OBJECTIVE: To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19.

DESIGN: Population based study.

SETTING: UK.

PARTICIPANTS: 1 650 052 individuals registered with a general practice contributing to Clinical Practice Research Datalink and newly diagnosed with at least one CVD from 1 January 2000 to 30 June 2019.

MAIN OUTCOME MEASURES: The primary outcome was incident diagnosis of CVD, comprising acute coronary syndrome, aortic aneurysm, aortic stenosis, atrial fibrillation or flutter, chronic ischaemic heart disease, heart failure, peripheral artery disease, second or third degree heart block, stroke (ischaemic, haemorrhagic, and unspecified), and venous thromboembolism (deep vein thrombosis or pulmonary embolism). Disease incidence rates were calculated individually and as a composite outcome of all 10 CVDs combined and were standardised for age and sex using the 2013 European standard population. Negative binomial regression models investigated temporal trends and variation by age, sex, and socioeconomic status.

RESULTS: The mean age of the population was 70.5 years and 47.6% (n=784 904) were women. The age and sex standardised incidence of all 10 prespecified CVDs declined by 19% during 2000-19 (incidence rate ratio 2017-19 v 2000-02: 0.80, 95% confidence interval 0.73 to 0.88). The incidence of coronary heart disease and stroke decreased by about 30% (incidence rate ratios for acute coronary syndrome, chronic ischaemic heart disease, and stroke were 0.70 (0.69 to 0.70), 0.67 (0.66 to 0.67), and 0.75 (0.67 to 0.83), respectively). In parallel, an increasing number of diagnoses of cardiac arrhythmias, valve disease, and thromboembolic diseases were observed. As a result, the overall incidence of CVDs across the 10 conditions remained relatively stable from the mid-2000s. Age stratified analyses further showed that the observed decline in coronary heart disease incidence was largely restricted to age groups older than 60 years, with little or no improvement in younger age groups. Trends were generally similar between men and women. A socioeconomic gradient was observed for almost every CVD investigated. The gradient did not decrease over time and was most noticeable for peripheral artery disease (incidence rate ratio most deprived v least deprived: 1.98 (1.87 to 2.09)), acute coronary syndrome (1.55 (1.54 to 1.57)), and heart failure (1.50 (1.41 to 1.59)).

CONCLUSIONS: Despite substantial improvements in the prevention of atherosclerotic diseases in the UK, the overall burden of CVDs remained high during 2000-19. For CVDs to decrease further, future prevention strategies might need to consider a broader spectrum of conditions, including arrhythmias, valve diseases, and thromboembolism, and examine the specific needs of younger age groups and socioeconomically deprived populations.

PMID:38925788 | DOI:10.1136/bmj-2023-078523

JACC Clin Electrophysiol. 2024 Jun;10(6):1203-1205. doi: 10.1016/j.jacep.2024.04.019.

NO ABSTRACT

PMID:38925722 | DOI:10.1016/j.jacep.2024.04.019

BMJ Open. 2024 Jun 25;14(6):e082134. doi: 10.1136/bmjopen-2023-082134.

ABSTRACT

OBJECTIVE: Although adverse childhood experiences (ACEs) are associated with poor health in adulthood, positive childhood experiences (PCEs) can reduce the risk of negative health outcomes. This study aimed to investigate whether PCEs in the community (CPCEs, ie, trusted adults other than parents, supportive friends, belongingness to school, or community traditions) would have an independent effect on better health outcomes and moderate the association between ACEs and adult illnesses.

DESIGN: Cross-sectional survey.

SETTING: Data were gathered from a nationwide, cross-sectional internet survey conducted in Japan in 2022.

PARTICIPANTS: This study included 28 617 Japanese adults aged 18-82 years (51.1% female; mean age=48.1 years).

PRIMARY AND SECONDARY OUTCOME MEASURES: The associations among self-reported ACEs, CPCEs before the age of 18 years and current chronic diseases (eg, cancer and depression) were investigated using multivariable logistic regression models.

RESULTS: CPCEs were associated with lower odds of adult diseases (such as stroke, chronic obstructive pulmonary disease (COPD), chronic pain, depression, suicidal ideation and severe psychological distress) after adjusting for ACEs. More CPCEs weakened the association between ACEs and adult diseases. Specifically, among those with ACEs, ≥3 CPCEs (vs 0-2 CPCEs) lowered the adjusted prevalence by ≥50% for stroke (2.4% to 1.2%), COPD (2.2% to 0.7%) and severe psychological distress (16.4% to 7.4%).

CONCLUSION: CPCEs could reduce ACE-related risk of poor physical and mental health in later life. Early-life interventions that enhance PCEs in schools and/or neighbourhoods are recommended.

PMID:38925696 | DOI:10.1136/bmjopen-2023-082134

BMJ Open. 2024 Jun 25;14(6):e078398. doi: 10.1136/bmjopen-2023-078398.

ABSTRACT

OBJECTIVES: This study aimed to develop a patient-centred approach to the burden of acute type A aortic dissection (ATAAD) through modelling. The main objective was to identify potential improvements in managing this life-threatening cardiovascular condition and to provide evidence-based recommendations to optimise outcomes.

DESIGN: We developed a predictive model along patient pathways to estimate the burden of ATAAD through the years of life lost (YLLs) metric. The model was created based on a systematic review of the literature and was parameterised using demographic data from the German healthcare environment. The model was designed to allow interactive simulation of different scenarios resulting from changes in key impact factors.

SETTING: The study was conducted using data from the German healthcare environment and results from the literature review.

PARTICIPANTS: The study included a comprehensive modelling of ATAAD cases in Germany but did not directly involve participants.

INTERVENTIONS: There were no specific interventions applied in this study based on the modelling design.

PRIMARY AND SECONDARY OUTCOME MEASURES: The single outcome measure was the estimation of YLL due to ATAAD in Germany.

RESULTS: Our model estimated 102 791 YLL per year for ATAAD in Germany, with 62 432 and 40 359 YLL for men and women, respectively. Modelling an improved care setting yielded 93 191 YLL or 9.3% less YLL compared with the current standard while a worst-case scenario resulted in 113 023 or 10.0% more YLL. The model is accessible at https://acuteaorticdissection.com/ to estimate custom scenarios.

CONCLUSIONS: Our study provides an evidence-based approach to estimating the burden of ATAAD and identifying potential improvements in the management of pathways. This approach can be used by healthcare decision-makers to inform policy changes aimed at optimising patient outcomes. By considering patient-centred approaches in any healthcare environment, the model has the potential to improve efficient care for patients suffering from ATAAD.

PMID:38925695 | DOI:10.1136/bmjopen-2023-078398

BMJ Open. 2024 Jun 25;14(6):e081538. doi: 10.1136/bmjopen-2023-081538.

ABSTRACT

BACKGROUND: Children living in food insecure households have poorer mental health outcomes compared with their food-secure peers; however, the relationship between the severity of food insecurity and diagnosed mental health conditions in young children remains unknown. This study examined the association between household food insecurity and reported diagnosed mental health conditions among children aged 5-11 years in Canada.

METHODS: This study included 16 216 children aged 5-11 years living in Canada, from the 2019 Canadian Health Survey on Children and Youth. We measured household food insecurity using the Household Food Security Survey Module. We measured diagnosed mental health conditions by parent/caregiver report of health professional-diagnosed anxiety, depression, autism spectrum disorder or attention-deficit/hyperactive disorder. We developed a multivariable logistic regression model to assess the association between severities of food insecurity and mental health, controlling for potentially confounding variables.

RESULTS: 17.0% of children lived in households reporting some level of food insecurity (5.4% marginal, 8.0% moderate and 3.6% severe). The prevalence of at least one diagnosed mental health condition in the same population was 10.9%. After adjusting for sociodemographic characteristics, children from marginal, moderate and severe food insecure households had a 1.39 (95% CI 0.99 to 1.97), 1.46 (95% CI 1.13 to 1.89) and 1.67 (95% CI 1.18 to 2.35) increased odds of having a diagnosed mental health condition, respectively.

CONCLUSION: Household food insecurity is associated with an increased presence of diagnosed mental health conditions in children aged 5-11 years. This study adds to the body of research showing that social and economic inequities, including household food insecurity, negatively impact the health of children.

PMID:38925691 | DOI:10.1136/bmjopen-2023-081538