Pharma 4.0: A deep dive top management commitment to successful Lean 4.0 implementation in Ghanaian pharma manufacturing sector.

The primary aim of this study is to assess the significance of top management commitment in the context of Lean 4.0 implementation within the pharmaceutical manufacturing industry in Ghana. The study seeks to understand and evaluate the overall effectiveness and achievements associated with adopting Lean 4.0. Employing a positivist mindset, the research utilizes an explanatory quantitative research design and a survey technique. Data collected from 181 employees of pharmaceutical companies in Ghana undergo analysis using SmartPLS (version 4) and IBM SPSS version 26. The study employs a combination of descriptive statistics to summarise data characteristics and inferential statistics to test various hypotheses related to Lean 4.0 adoption. The analysis reveals that the successful integration of lean methods and Industry 4.0 technologies requires meticulous management. Simultaneously, individual implementations of lean principles and Industry 4.0 technologies positively impact business performance. Surprisingly, the study does not observe a substantial positive influence of Lean 4.0 on corporate performance, suggesting that immediate improvements in efficiency or profitability may not result from the adoption of this framework. This research contributes to the field by highlighting the need for careful management in integrating lean methods and Industry 4.0 technologies. It also emphasizes the positive impacts of lean principles and Industry 4.0 technology on business performance. The unexpected finding regarding the lack of immediate improvements in corporate efficiency or profitability with Lean 4.0 adoption prompts considerations of initial implementation challenges or the organization's need for time to adapt to this integrated approach.

Systemic Factors Affecting Orthodontic Treatment Outcomes and Prognosis - Part 1.

This article explores the intersection of various systemic conditions with orthodontic treatment. Renal diseases, including chronic kidney disease and renal transplant, present challenges such as delayed tooth eruption and gingival overgrowth, necessitating careful orthodontic planning and collaboration with physicians. Liver diseases, particularly hepatitis, heighten the risk of periodontal disease and mandate strict infection control measures during orthodontic procedures. Ehlers-Danlos syndrome poses challenges related to collagen fragility, rapid tooth movement, and orthodontic relapse. Autoimmune diseases like diabetes mellitus and juvenile idiopathic arthritis require tailored orthodontic approaches considering oral complications and joint involvement.

Systemic Factors Affecting Orthodontic Treatment Outcomes and Prognosis-Part 2.

This article explores the various challenges systemic conditions can pose before and during orthodontic treatment. Cardiovascular conditions like infective endocarditis require antibiotic prophylaxis before certain orthodontic procedures are started. Patients with bleeding disorders require special considerations in regards to viral infection risk and maintenance of excellent atraumatic oral hygiene. Orthodontists play an important role in early identification of signs and symptoms of eating disorders and should deal with these patients sensitively. Congenital disorders, craniofacial anomalies, and nutritional deficiencies require special considerations and should be addressed appropriately before orthodontic treatment is started.

Impact of Genetic Ancestry on T-cell Acute Lymphoblastic Leukemia Outcomes.

The influence of genetic ancestry on biology, survival outcomes, and risk stratification in T-cell Acute Lymphoblastic Leukemia (T-ALL) has not been explored. Genetic ancestry was genomically-derived from DNA-based single nucleotide polymorphisms in children and young adults with T-ALL treated on Children's Oncology Group trial AALL0434. We determined associations of genetic ancestry, leukemia genomics and survival outcomes; co-primary outcomes were genomic subtype, pathway alteration, overall survival (OS), and event-free survival (EFS). Among 1309 patients, T-ALL molecular subtypes varied significantly by genetic ancestry, including increased frequency of genomically defined ETP-like, MLLT10, and BCL11B-activated subtypes in patients of African ancestry. In multivariable Cox models adjusting for high-risk subtype and pathways, patients of Admixed American ancestry had superior 5-year EFS/OS compared with European; EFS/OS for patients of African and European ancestry were similar. The prognostic value of five commonly altered T-ALL genes varied by ancestry - including NOTCH1 , which was associated with superior OS for patients of European and Admixed American ancestry but non-prognostic among patients of African ancestry. Furthermore, a published five-gene risk classifier accurately risk stratified patients of European ancestry, but misclassified patients of African ancestry. We developed a penalized Cox model which successfully risk stratified patients across ancestries. Overall, 80% of patients had a genomic alteration in at least one gene with differential prognostic impact by genetic ancestry. T-ALL genomics and prognostic associations of genomic alterations vary by genetic ancestry. These data demonstrate the importance of incorporating genetic ancestry into analyses of tumor biology for risk classification algorithms.

The Emerging Field of Viroimmunotherapy for Pediatric Brain Tumors.

Pediatric brain tumors are the most common solid tumors in children. Even to date, with the advances in multimodality therapeutic management, survival outcomes remain dismal in some types of tumors, such as pediatric-type diffuse high-grade gliomas or central nervous system (CNS) embryonal tumors. Failure to understand the complex molecular heterogeneity and the elusive tumor and microenvironment interplay continues to undermine therapeutic efficacy. Developing a strategy that would improve survival for these fatal tumors remains unmet in pediatric neuro-oncology. Oncolytic viruses (OVs) are emerging as a feasible, safe, and promising therapy for brain tumors. The new paradigm in virotherapy implies that the direct cytopathic effect is followed, under certain circumstances, by an antitumor immune response responsible for the partial or complete debulking of the tumor mass. OVs alone or combined with other therapeutic modalities have been primarily used in adult neuro-oncology. A surge in encouraging preclinical studies in pediatric brain tumor models recently led to the clinical translation of OVs with encouraging results in these tumors. In this review, we summarize the different virotherapy tested in preclinical and clinical studies in pediatric brain tumors, and we discuss the limitations and future avenues necessary to improve the response of these tumors to this type of therapy.

The medical and functional burden of surviving childhood ependymoma: A population-based study in Ontario, Canada.

BACKGROUND: Few studies have characterized the burden of late effects among childhood ependymoma survivors. To address this gap, we examined these sequelae using real-world health services data in a population-based ependymoma survivor cohort. METHODS: All individuals younger than 18 years diagnosed with an ependymoma in Ontario, Canada between 1987 and 2015 who had survived at least 5 years from their latest pediatric cancer event (index date) were matched 1:5 with population controls. Following linkage with provincial health services data, the cumulative incidences of multiple medical and functional outcomes between survivors and controls were compared. RESULTS: Among 96 survivors, 77.1% had been irradiated and 9.4% had received cisplatin. At 10 years post-index, survivors were at significantly higher risk of all-cause mortality (7.1%, 95% confidence interval [CI]: 1.0-13.3 vs. 0.3%, 95% CI: 0.0-1.0; p = .0002), non-obstetric hospitalization (45.1%, 95% CI: 32.6-56.7 vs. 10.6%, 95% CI: 7.6-14.1; p < .0001), stroke (6.5%, 95% CI: 2.3-13.7 vs. 0%; p < .0001), severe hearing loss requiring an amplification device (7.5%, 95% CI: 2.7-15.7 vs. 0%; p < .0001), receiving homecare service (27.6%, 95% CI: 18.5-37.5 vs. 7.7%, 95% CI: 5.3-10.7; p < .0001), and submitting a disability support prescription claim (24.0%, 95% CI: 14.8-34.3 vs. 5.4%, 95% CI: 3.5-7.8; p < .0001) compared to controls. CONCLUSIONS: Pediatric ependymoma survivors are highly vulnerable to severe late sequelae, including death, stroke, severe hearing loss, and disability. Urgent efforts are needed to improve risk-stratification approaches that mitigate exposure to toxic therapies for children with lower risk disease. Interventions to prevent or decrease the risk of developing late sequelae are critical to optimizing survivor long-term health.

Empowering sustainable manufacturing: Unleashing digital innovation in spool fabrication industries.

In industrial landscapes, spool fabrication industries play a crucial role in the successful completion of numerous industrial projects by providing prefabricated modules. However, the implementation of digitalized sustainable practices in spool fabrication industries is progressing slowly and is still in its embryonic stage due to several challenges. To implement digitalized sustainable manufacturing (SM), digital technologies such as Internet of Things, Cloud computing, Big data analytics, Cyber-physical systems, Augmented reality, Virtual reality, and Machine learning are required in the context of sustainability. The scope of the present study entails prioritization of the enablers that promote the implementation of digitalized sustainable practices in spool fabrication industries using the Improved Fuzzy Stepwise Weight Assessment Ratio Analysis (IMF-SWARA) method integrated with Triangular Fuzzy Bonferroni Mean (TFBM). The enablers are identified through a systematic literature review and are validated by a team of seven experts through a questionnaire survey. Then the finally identified enablers are analyzed by the IMF-SWARA and TFBM integrated approach. The results indicate that the most significant enablers are management support, leadership, governmental policies and regulations to implement digitalized SM. The study provides a comprehensive analysis of digital SM enablers in the spool fabrication industry and offers guidelines for the transformation of conventional systems into digitalized SM practices.

Telehealth Visits have Lower Non-attendance than Traditional Orthopaedic Clinic Visits.

The use of telemedicine has rapidly expanded in the wake of the COVID pandemic, but its effect on patient attendance remains unknown for different clinicians. This study compared traditional in-clinic visits with telehealth visits by retrospectively reviewing all scheduled orthopaedic clinic visits. Results demonstrated lower rates of cancellations in patients scheduled for telehealth visits as compared to in-clinic visits, during the initial COVID pandemic. In general, physicians can expect a lower cancellation rate than non-physician practitioners.

Dilemma with implant placement in patients with florid cemento-osseous dysplasia: A literature review.

METHODOLOGY: An electronic search was done in PUBMED, SCOPUS, and a hand search was done in radiology, periodontology, and oral surgery journals. The search yielded 428 results, from which only 6 articles were selected for this literature review. Both prospective and retrospective studies were included. Clinical studies with information on the pre-implant condition of the site, detailed implant procedure, and follow-up after implant placement of more than 6 months were only considered for this review. RESULTS AND CONCLUSION: Limited clinical studies, shorter follow-up periods were the shortcomings of this review. However, it can be summarized that dental implants should not be placed at the site of FCOD, however can be placed at adjacent sites. Variations in implant type or the implant length had no bearing on the survival of implants at the sites of FCOD.

Impact of Propofol Exposure on Neurocognitive Outcomes in Children With High-Risk B ALL: A Children's Oncology Group Study.

PURPOSE: Many children treated for ALL develop long-term neurocognitive impairments. Increased risk of these impairments is associated with treatment and demographic factors. Exposure to anesthesia is an additional possible risk factor. This study evaluated the impact of cumulative exposure to anesthesia on neurocognitive outcomes among a multicenter cohort of children with ALL. METHODS: This study was embedded in AALL1131, a Children's Oncology Group phase III trial for patients with high-risk B-ALL. In consenting patients age 6-12 years, prospective uniform assessments of neurocognitive function were performed during and at 1 year after completion of therapy. Exposure to all episodes of anesthetic agents was abstracted. Multivariable linear regression models determined associations of cumulative anesthetic agents with the primary neurocognitive outcome reaction time/processing speed (age-normed) at 1 year off therapy, adjusting for baseline neurocognitive score, age, sex, race/ethnicity, insurance status (as a proxy for socioeconomic status), and leukemia risk group. RESULTS: One hundred and forty-four children, 76 (52.8%) males, mean age of 9.1 (min-max, 6.0-12.0) years at diagnosis, underwent a median of 27 anesthetic episodes (min-max, 1-37). Almost all patients were exposed to propofol (140/144, 97.2%), with a mean cumulative dose of 112.3 mg/kg. One year after therapy, the proportion of children with impairment (Z-score ≤-1.5) was significantly higher compared with a normative sample. In covariate-adjusted multivariable analysis, cumulative exposure to propofol was associated with a 0.05 Z-score decrease in reaction time/processing speed per each 10 mg/kg propofol exposure (P = .03). CONCLUSION: In a multicenter and uniformly treated cohort of children with B-ALL, cumulative exposure to propofol was an independent risk factor for impairment in reaction time/processing speed 1 year after therapy. Anesthesia exposure is a modifiable risk, and opportunities to minimize propofol use should be considered.

Validation and Suitability Assessment of Multiplex Mesoscale Discovery Immunogenicity Assay for Establishing Serological Signatures Using Vaccinated, Non-Vaccinated and Breakthrough SARS-CoV-2 Infected Cases.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for the establishment of serological signatures during vaccination and or infection. We describe here the validation and evaluation of an electro-chemiluminescence (ECL)-based Mesoscale Discovery assay (MSD) for estimation of total and functional IgG relative to SARS-CoV-2 spike, nucleocapsid and receptor binding (RBD) proteins in human serum samples to establish serological signatures of SARS-CoV-2 natural infection and breakthrough cases. The 9-PLEX assay was validated as per ICH, EMA, and US FDA guidelines using a panel of sera samples, including the NIBSC/WHO reference panel (20/268). The assay demonstrated high specificity and selectivity in inhibition assays, wherein the homologous inhibition was more than 85% and heterologous inhibition was below 10%. The assay also met predetermined acceptance criteria for precision (CV < 20%), accuracy (70-130%) and dilutional linearity. The method's applicability to serological signatures was demonstrated using sera samples (n = 45) representing vaccinated, infected and breakthrough cases. The method was able to establish distinct serological signatures and thus provide a potential tool for seroprevalence of SARS-CoV-2 during vaccination or infection.

Computed Tomography Angiography After Transcatheter and Surgical Aortic Interventions.

This comprehensive article reviews the complex realm of aortic surgical and endovascular interventions, focusing on the aortic root, ascending aorta, aortic arch, descending aorta, and abdominal aorta. It outlines the nuances of various procedures, emphasizing the importance of computed tomography angiography acquisition for an accurate assessment. Detailed discussions encompass expected postsurgical/endovascular findings and complications, covering various scenarios, from hematoma and infection to pseudoaneurysms and graft-related issues. This article serves as a crucial resource for radiologists, offering invaluable insights into the complexities of aortic interventions and their subsequent imaging, fostering a comprehensive understanding of diagnostic and management strategies.

Fever at Time of Leukemia Diagnosis in Children: Predictor of Bloodstream Infection or Catheter Removal?

PURPOSE: To assess the incidence of fever at diagnosis in children with leukemia and determine if fever at diagnosis is a predictor of bloodstream infection (BSI) or central venous access device (CVAD) removal for infection either within the first 30 days or between 30 and 90 days after CVAD insertion. MATERIALS AND METHODS: One hundred fifty-one patients with acute leukemia (July 1, 2018, to December 31, 2020) who underwent a CVAD insertion within 2 weeks of diagnosis were included. Patient data included demographic characteristics, fever at diagnosis, CVAD type, antibiotics before and/or on the day of CVAD insertion, BSI incidence, BSI rates per 1,000 catheter days, and need for catheter removal after CVAD insertion within 30 days and between 30 and 90 days. RESULTS: Patients with fever at diagnosis had a significantly higher incidence of BSI within the first 30 days after CVAD insertion (17/23) than that among patients without fever (6/23) (P = .046) at diagnosis. No statistically significant difference was observed in the incidence of BSI between 30 and 90 days after CVAD insertion between patients with fever (5/11) and those without fever at diagnosis (6/11) (P = .519). Fever at diagnosis was not a predictor of CVAD removal within 30 days (9 patients required CVAD removal; 7/9 had fever and 2/9 had no fever) (P = .181) or between 30 and 90 days (4 patients required CVAD removal; 1/4 had fever and 3/4 had no fever at diagnosis) (P = .343) after insertion. CONCLUSIONS: Fever at diagnosis in patients with leukemia is not a predictor of CVAD removal for infection.

Effect of Antibiotic Prophylaxis on Infection Rates in Pediatric Supracondylar Humerus Fractures Treated with Closed Reduction and Percutaneous Pinning: A Prospective Double-Blinded Randomized Controlled Trial.

BACKGROUND: Supracondylar humerus fractures (SCHFs) are the most common elbow fracture in the pediatric population. In the case of displaced fractures, closed reduction and percutaneous Kirschner wire pinning (CRPP) is commonly performed. Infection rates are between 0 and 7%; however, retrospective studies have shown no benefit of preoperative antibiotics. There continues to be notable variability in antibiotic usage based on surgeon preference and local institutional policy. We conducted a double-blinded, randomized controlled trial to evaluate whether antibiotic prophylaxis reduces the risk of infection in pediatric SCHF patients treated with CRPP. METHODS: Pediatric patients with displaced SCHF who presented to a pediatric hospital were enrolled and randomized into two groups. Group I received one dose of prophylactic antibiotics (25 mg/kg cefazolin IV up to 1g or clindamycin 10 mg/kg up to 600 mg/kg IV in the case of cefazolin allergy). Group II received placebo (10-mL prefilled syringe of normal saline). All patients underwent CRPP and casting followed by pin removal 3 to 6 weeks after the initial procedure. The presence of pin-site infection, erythema, drainage, septic arthritis, and osteomyelitis was recorded. RESULTS: One hundred sixty patients were enrolled in the study. Eighty-two patients were randomized to receive antibiotics, and 78 patients were randomized to placebo. No difference was seen in the rate of infection between the treatment groups (1.2% in the antibiotic group versus 1.3% in the placebo group; P = 1.00). Presence of purulent drainage (0.0% versus 1.3%; P = 0.49), septic arthritis (0.0% versus 0.0%; P = 1.00), and osteomyelitis (1.2% versus 0.0%; P = 1.00) was similar in both groups. No difference in the need for additional antibiotics (1.2% versus 1.3%; P = 1.00) or additional surgery (1.2% versus 0.0%; P = 1.00) was found between groups. DISCUSSION: The use of antibiotic prophylaxis did not affect the risk of infection in pediatric patients who underwent CRPP for displaced SCHF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03261830. LEVEL OF EVIDENCE: Therapeutic Level I.

Cost and cost-effectiveness of immunotherapy in childhood ALL: A systematic review.

Survival rates for pediatric acute lymphoblastic leukemia (pALL) have improved dramatically; relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) remains challenging. Immunotherapies are rapidly evolving treatments for r/r ALL with limited cost-effectiveness data. This study identifies existing economic evaluations of immunotherapy in pALL and summarizes cost-effectiveness. Medline, Embase, and other databases were searched from inception to October 2022. Cost-effectiveness analyses evaluating immunotherapy in pALL were included. Costs reported in 2021 USD. Of 2960 studies, 11 met inclusion criteria. Tisagenlecleucel was compared to standard of care, clofarabine monotherapy, clofarabine combination therapy, or blinatumomab. No studies have evaluated blinatumomab or inotuzumab ozogamicin. Six studies found tisagenlecleucel to be cost-effective, five of which were supported by Novartis. Four found that it had the potential to be cost-effective, and one found that it was not cost-effective. The cost-effectiveness of tisagenlecleucel was highly dependent on list price and cure rates. This study can inform the use of tisagenlecleucel in pALL.

Protocol for the ONLOOP trial: pragmatic randomized trial evaluating a province-wide system of personalized reminders for evidence-based surveillance tests in adult survivors of childhood cancer in Ontario.

BACKGROUND: Childhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time. METHODS: This is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP's impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants' consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later. The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed. DISCUSSION: The results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05832138.

Nature-inspired peptide of MtDef4 C-terminus tail enables protein delivery in mammalian cells.

Cell-penetrating peptides show promise as versatile tools for intracellular delivery of therapeutic agents. Various peptides have originated from natural proteins with antimicrobial activity. We investigated the mammalian cell-penetrating properties of a 16-residue peptide with the sequence GRCRGFRRRCFCTTHC from the C-terminus tail of the Medicago truncatula defensin MtDef4. We evaluated the peptide's ability to penetrate multiple cell types. Our results demonstrate that the peptide efficiently penetrates mammalian cells within minutes and at a micromolar concentration. Moreover, upon N-terminal fusion to the fluorescent protein GFP, the peptide efficiently delivers GFP into the cells. Despite its remarkable cellular permeability, the peptide has only a minor effect on cellular viability, making it a promising candidate for developing a cell-penetrating peptide with potential therapeutic applications.

Risk factors and clinical impact of thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: A report from CYP-C.

Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TEind ) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T-cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TEind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T-cell phenotype and mortality but did not predict induction failure.

Late mortality among 5-year survivors of childhood cancer: A systematic review and meta-analysis.

BACKGROUND: Childhood cancer survivors are at increased risk of late mortality (death ≥5 years after diagnosis) from cancer recurrence and treatment-related late effects. The authors conducted a systematic review and meta-analysis to provide comprehensive estimates of late mortality risk among survivors internationally and to investigate differences in risk across world regions. METHODS: Health sciences databases were searched for cohort studies comprised of 5-year childhood cancer survivors in which the risk of mortality was evaluated across multiple cancer types. Eligible studies assessed all-cause mortality risk in survivors relative to the general population using the standardized mortality ratio (SMR). The absolute excess risk (AER) was assessed as a secondary measure to examine excess deaths. Cause-specific mortality risk was also assessed, if reported. SMRs from nonoverlapping cohorts were combined in subgroup meta-analysis, and the effect of world region was tested in univariate meta-regression. RESULTS: Nineteen studies were included, and cohort sizes ranged from 314 to 77,423 survivors. Throughout survivorship, SMRs for all-cause mortality generally declined, whereas AERs increased after 15-20 years from diagnosis in several cohorts. All-cause SMRs were significantly lower overall in North American studies than in European studies (relative SMR, 0.63; 95% confidence interval, 0.49-0.80). SMRs for subsequent malignant neoplasms and for cardiovascular, respiratory, and external causes did not vary significantly between world regions. CONCLUSIONS: The current findings suggest that late mortality risk may differ significantly between world regions, but these conclusions are based on a limited number of studies with considerable heterogeneity. Reasons for regional differences remain unclear but may be better elucidated through future analyses of individual-level data.