Brain-derived neurotrophic factor (BDNF) epigenomic modifications and brain-related phenotypes in humans: A systematic review.

Epigenomic modifications of the brain-derived neurotrophic factor (BDNF) gene have been postulated to underlie the pathogenesis of neurodevelopmental, psychiatric, and neurological conditions. This systematic review summarizes current evidence investigating the association of BDNF epigenomic modifications (DNA methylation, non-coding RNA, histone modifications) with brain-related phenotypes in humans. A novel contribution is our creation of an open access web-based application, the BDNF DNA Methylation Map, to interactively visualize specific positions of CpG sites investigated across all studies for which relevant data were available. Our literature search of four databases through September 27, 2021 returned 1701 articles, of which 153 met inclusion criteria. Our review revealed exceptional heterogeneity in methodological approaches, hindering the identification of clear patterns of robust and/or replicated results. We summarize key findings and provide recommendations for future epigenomic research. The existing literature appears to remain in its infancy and requires additional rigorous research to fulfill its potential to explain BDNF-linked risk for brain-related conditions and improve our understanding of the molecular mechanisms underlying their pathogenesis.

Characterizing the Influence of Television Health Entertainment Narratives in Lay Populations: A Scoping Review.

OBJECTIVE: To conduct a scoping review of published literature examining the influence of health storylines from fictional television programs on viewers. DATA SOURCE: We performed literature searches in Medline, PsycINFO, and Mass Media Complete in October 2021, and examined bibliographies of included articles and conducted forward searching using Web of Science with included articles. STUDY INCLUSION AND EXCLUSION CRITERIA: Selected studies were required to be original research published in English, involve exposure to fictional television programming by individuals not in the medical field, and assess associations between exposure and health-related outcomes. DATA EXTRACTION: Article screening and data abstraction were performed by two independent researchers using DistillerSR (Cohen's κ range: .73-1.00). DATA SYNTHESIS: We analyzed and qualitatively described the data using methods of scoping reviews described by PRISMA-ScR. RESULTS: Of 5,537 unique records identified, 165 met inclusion criteria. The most frequently studied program was ER (n = 22, 13.3%). Most studies had adult participants (n = 116, 70.3%) and used quantitative methods (n = 136, 82.4%). The most frequently examined health topics were sexual behavior (n = 28, 17.0%) and mental health (n = 28, 17.0%). Exposure had a positive influence on viewers' health-related outcomes in 28.5% (n = 47) of studies. CONCLUSION: Health storylines on fictional television influence viewers. Future research could address gaps identified in this review to further elucidate the influence of this programming on health promotion and disease prevention.

Transmission visualizations of healthcare infection clusters: A scoping review.

Objective: To evaluate infectious pathogen transmission data visualizations in outbreak publications. Design: Scoping review. Methods: Medline was searched for outbreak investigations of infectious diseases within healthcare facilities that included ≥1 data visualization of transmission using data observable by an infection preventionist showing temporal and/or spatial relationships. Abstracted data included the nature of the cluster(s) (pathogen, scope of transmission, and individuals involved) and data visualization characteristics including visualization type, transmission elements, and software. Results: From 1,957 articles retrieved, we analyzed 30 articles including 37 data visualizations. The median cluster size was 20.5 individuals (range, 7-1,963) and lasted a median of 214 days (range, 12-5,204). Among the data visualization types, 10 (27%) were floor-plan transmission maps, 6 (16%) were timelines, 11 (30%) were transmission networks, 3 (8%) were Gantt charts, 4 (11%) were cluster map, and 4 (11%) were other types. In addition, 26 data visualizations (70%) contained spatial elements, 26 (70%) included person type, and 19 (51%) contained time elements. None of the data visualizations contained contagious periods and only 2 (5%) contained symptom-onset date. Conclusions: The data visualizations of healthcare-associated infectious disease outbreaks in the systematic review were diverse in type and visualization elements, though no data visualization contained all elements important to deriving hypotheses about transmission pathways. These findings aid in understanding the visualizing transmission pathways by describing essential elements of the data visualization and will inform the creation of a standardized mapping tool to aid in earlier initiation of interventions to prevent transmission.

Surgical management for mechanical complications of acute myocardial infarction: a systematic review of long-term outcomes.

Background: Mechanical complications following acute myocardial infarction (AMI), though rare, are associated with significant morbidity and mortality. Surgical management remains a mainstay of therapy for these complications. The purpose of this review is to evaluate long-term outcomes data of surgical management for postinfarction free wall rupture, ventricular septal defect, papillary muscle rupture, and pseudoaneurysm. Methods: An electronic literature search was performed to identify original studies reporting long-term outcomes data of surgical management of one of the four mechanical complications following AMI. Studies were considered to have long-term outcomes if they at minimum included survival or mortality data up to one year. Results: A total of 285 studies were identified from the literature search. Of these, 29 studies with long-term survival data on surgically managed mechanical complications of AMI are included in the review. The majority of these are retrospective cohort studies or single-center case series. Five studies are included on free wall rupture, 18 on ventricular septal defect, 4 on papillary muscle rupture, and 2 on pseudoaneurysm. Detailed results are tabulated according to complication. Conclusions: Long-term surgical outcomes of postinfarction mechanical complications remain understudied. Outcomes for ventricular septal defect repair are better represented in the literature than are outcomes for other mechanical complications, though available studies are still limited by small sample sizes and retrospective design. Further research is warranted, particularly for outcomes of acute pseudoaneurysm repair.

Racial/ethnic disparities in use of surveillance mammogram among breast cancer survivors: a systematic review.

BACKGROUND: Increasing number of breast cancer survivors in the USA have led to greater focus on the long-term health outcomes and surveillance care among these women. However limited evidence exists of use of surveillance mammography among breast cancer survivors and how it varies across racial/ethnic groups. METHODS: We conducted a systematic review of the literature to explore disparities in use of surveillance mammogram among women breast cancer survivors by searching for relevant studies published between 2000 and 2020 from Medline (Ovid), PubMed (National Library of Medicine), and PsycINFO (Ovid) bibliographic databases. Two authors independently screened titles, abstracts, and full texts of all articles that reported surveillance mammography use across racial/ethnic groups. Data on study design, screening eligibility, sample size, operational definition, and/or measure of the use of a surveillance mammogram among breast cancer survivors and the association between race/ethnicity and use of a surveillance mammogram were summarized in the evidence tables. RESULTS: We identified 1544 records from the three databases, and 30 studies examined the use of surveillance mammograms among breast cancer survivors across race/ethnic groups. Of these, 21 provided adjusted estimates of racial/ethnic disparities in use of surveillance mammograms, and 15 of these reported statistically significant disparities. In summary, most studies reported that non-white women (mainly Blacks and Hispanics) were less likely to receive a timely surveillance mammogram compared to White. CONCLUSION: This study extends the evidence of racial/ethnic disparities beyond completion of initial treatment by finding similar disparities in receipt of surveillance mammograms among breast cancer survivors. IMPLICATION FOR CANCER SURVIVORS: Our findings identify a need to improve efforts to increase post-treatment use of surveillance mammography among racial/ethnic minority women to reduce these gaps and improve overall clinical and quality of life outcomes.

Effects of music participation for mild cognitive impairment and dementia: A systematic review and meta-analysis.

OBJECTIVES: To examine randomized controlled trials with active music-making interventions, in which older adults with probable mild cognitive impairment (MCI) or dementia physically participate in music, and their effects on cognitive functioning, emotional well-being, and social engagement. Participating in music-making is engaging and has shown diverse benefits. Additionally, this review categorized the music activities of each intervention. DESIGN: Systematic review and meta-analysis. SETTING: Long-term care facilities, day centers, specialty outpatient units, and community. METHODS: Published randomized controlled trials of active music-making interventions to support older adults with probable MCI or dementia were identified (to March 15, 2021) using searches on Medline (Ovid), APA PsycInfo (Ovid), CINAHL (Ebsco), and Embase (Elsevier). The outcomes were cognitive functioning, emotional well-being, and social engagement, including self- and clinician-reported measures such as the Mini-Mental State Examination, Positive and Negative Affect Schedule, and the Beck Depression Inventory. Studies were critically appraised and studies with similar methodology were meta-analyzed. PARTICIPANTS: Older adults with probable MCI and mild or moderate dementia. RESULTS: A total of 21 studies with 1472 participants were analyzed for potential effect sizes and intervention activities. Of the 21 studies, nine studies recruiting a total of 495 participants were used to produce a random-effects meta-analytic model for cognitive functioning. Music showed a small, positive effect on cognitive functioning; the combined standard mean difference for the experimental and control group was 0.30 (95% confidence interval [CI] 0.10, 0.51). There was low study heterogeneity, with an I2 of 24% (p = 0.004). Individual studies for emotional well-being in terms of quality of life and mood showed positive effect sizes, d = 1.08 and d = 1.74, respectively. [Corrections added on July 8, 2021, after first online publication: The preceding sentences were revised from: "… control group was 0.31 (95% confidence interval [CI] 0.10,0.52). There was low study heterogeneity, with an I2 of 25% (p = 0.004)."] CONCLUSION: This review shows that music-making has a small but statistically significant effect on cognitive functioning for older adults with probable MCI or dementia. Future music interventions can benefit from rigorous intervention protocols that isolate specific activities.

Measures of Organizational Culture and Climate in Primary Care: a Systematic Review.

BACKGROUND: Primary care is increasingly contributing to improving the quality of patient care. This has imposed significant demands on clinicians with rising needs and limited resources. Organizational culture and climate have been found to be crucial in improving workforce well-being and hence quality of care. The objectives of this study are to identify organizational culture and climate measures used in primary care from 2008 to 2019 and evaluate their psychometric properties. METHODS: Data sources include PubMed, PsycINFO, HAPI, CINAHL, and Mental Measurements Yearbook. Bibliographies of relevant articles were reviewed and a cited reference search in Scopus was performed. Eligibility criteria include primary health care professionals, primary care settings, and use of measures representing the general concept of organizational culture and climate. Consensus-Based Standards for the selection of health Measurement Instruments (COSMIN) guidelines were followed to evaluate individual studies for methodological quality, rate results of measurement properties, qualitatively pool studies by measure, and grade evidence. RESULTS: Of 1745 initial studies, 42 studies met key study inclusion criteria, with 27 measures available for review (16 for organizational culture, 11 for organizational climate). There was considerable variability in measures, both conceptually and in psychometric quality. Many reported limited or no psychometric information. DISCUSSION: Notable measures selected for frequent use and strength and applicability of measurement properties include the Culture Questionnaire adapted for health care settings, Practice Culture Assessment, and Medical Group Practice Culture Assessment for organizational culture. Notable climate measures include the Nurse Practitioner Primary Care Organizational Climate Questionnaire, Practice Climate Survey, and Task and Relational Climate Scale. This synthesis and appraisal of organizational culture and climate measures can help investigators make informed decisions in choosing a measure or deciding to develop a new one. In terms of limitations, ratings should be considered conservative due to adaptations of the COSMIN protocol for clinician populations. PROSPERO REGISTRATION NUMBER: CRD 42019133117.

Linear Scleroderma of the Head - Updates in management of Parry Romberg Syndrome and En coup de sabre: A rapid scoping review across subspecialties.

To provide an update on the current management, including evaluation and treatment, and the available diagnostic tools for linear scleroderma of the head, i.e., Parry-Romberg Syndrome and en coup de sabre (PRS/ECDS). A rapid scoping review of the literature was conducted to include manuscripts published in English between 2010 and 2019. Literature searches were performed in PubMed and EMBASE databases. The were analyzed for descriptive statistic reporting. This study reviewed 215 manuscripts reporting these 1430 patients. Surgical reports comprised the majority of the reviewed literature. Most PRS/ECDS did not appear to receive comprehensive multisubspecialty evaluation for extracutaneous manifestations; 21% of cases noted neurological screening, 4% noted dental screening, and 3% noted ophthalmologic screening. Methotrexate and glucocorticoids remain the most frequent choice for immunosuppressive treatment, though fewer than 7% of patients reported receiving systemic medical therapies. Surgical procedures for cosmetic or functional improvement were common (59%) among the reported patients. Autologous fat grafting was the most frequently utilized cosmetic treatment (50% of procedures) followed by free flap transfers (24% of procedures). There is ongoing need for standardized evaluation, monitoring, and treatment to prevent morbidity in PRS/ECDS, especially in children. When these patients are managed by rheumatologists, methotrexate, and steroids remain the first-line treatment, but a review of the published literature reflects that this may be a minority. Most PRS/ECDS patients are not evaluated in a multidisciplinary fashion. We propose comprehensive evaluations across subspecialties at the baseline and follow-up levels to monitor disease activity and record extracutaneous manifestations, treatment algorithms, and surgical intervention considerations.

Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.

BACKGROUND: CpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis. METHODS: We searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques. RESULTS: The pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21-24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries. CONCLUSION: Although no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.

Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials.

BACKGROUND: Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients. METHODS: We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients. RESULTS: We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients. CONCLUSION: Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management.

Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.

How low should we go: A systematic review and meta-analysis of the impact of restrictive red blood cell transfusion strategies in oncology.

BACKGROUND: Most non-oncologic clinical practice guidelines recommend restrictive allogeneic blood transfusion practices; however, there is a lack of consensus regarding the best transfusion practice in oncology. We conducted a systematic review of the literature to compare the efficacy and safety of restrictive versus liberal transfusion strategies in patients with cancer. METHODS: A literature search using MEDLINE, PUBMED and EMBASE identified all controlled studies comparing the use of restrictive with liberal transfusion in adult oncology participants up to August 10, 2015. Two review authors independently assessed studies for inclusion, extracted data and appraised the quality of the included studies. The primary outcomes of interest were blood utilization and all-cause mortality. RESULTS: Out of 4241 citations, six studies (3 randomized and 3 non-randomized) involving a total of 983 patients were included in the final review. The clinical context of the studies varied with 3 chemotherapy and 3 surgical studies. The overall risk of bias in all studies was moderate to high. Restrictive transfusion strategies were associated with a 36% reduced risk of receiving a perioperative transfusion (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.49-0.83). There was no difference in mortality between the strategies (RR 1.00, 95% CI 0.32-3.18). There were no differences in adverse events reported between the restrictive and liberal transfusion strategies. CONCLUSION: Restrictive strategy appears to decrease blood utilization without increasing morbidity or mortality in oncology. This review is limited by a paucity of high quality studies on this topic. Better designed studies are warranted.

Cost Effectiveness of Chemotherapeutic Agents and Targeted Biologics in Ovarian Cancer: A Systematic Review.

BACKGROUND: Adjuvant chemotherapy is a key component of advanced ovarian cancer treatment, when surgery alone is not sufficient. Recurrence is common in ovarian cancer patients and most women require prolonged second-line and higher-line chemotherapy. With newer targeted therapies, modest improvements in survival and quality of life may be attained at substantial cost, but the relative economic efficiency of these newer agents remains unknown. OBJECTIVE: We undertook this systematic review to comprehensively evaluate the cost-effectiveness of various chemotherapeutic and targeted therapy alternatives for ovarian cancer. METHODS: We searched Medline, PubMed, and Embase databases to identify economic evaluations published over the last 18 years (1996-2014). From the 2513 unique papers retrieved, 74 full texts were selected for full-text review based on a priori eligibility criteria. Two authors independently reviewed these articles to determine eligibility for final review. The quality of the included studies was assessed using the Quality of Health Economic Studies (QHES). RESULTS: A total of 28 studies were included for reporting. Administration of intravenous cisplatin-paclitaxel combination chemotherapy for first-line treatment was the most cost-effective alternative (2014 US dollars [USD] equivalent incremental cost-effectiveness ratio [ICER] ~US$17,000-US$27,000 per life year gained [LYG]), while the use of bevacizumab did not demonstrate similar value for money (2014 USD equivalent ICER was greater than US$200,000 per quality-adjusted life-year [QALY]). For second-line treatment, the use of platinum-paclitaxel combination or platinum monotherapy was cost-effective compared with platinum monotherapy or best supportive care, respectively, in women with recurrent platinum-sensitive disease. For patients with partial platinum sensitivity, pegylated liposomal doxorubicin (PLD) plus trabectedin may be cost-effective (2014 USD equivalent ICER was ~US$57,000-US$62,000 per QALY) compared with PLD alone. For recurrent platinum-resistant cases, there was limited evidence to conclude the most valuable treatment; though one study showed that best supportive care was most cost-effective, while second-line monotherapy with doxorubicin (2014 USD equivalent ICER was ~US$90,000 per LYG) may also be cost-effective compared with best supportive care. CONCLUSIONS: Despite varying methodological approaches and multiple sources for cost and effectiveness inputs, this systematic review demonstrated that standard platinum-taxane combination chemotherapy for first-line treatment was most cost-effective. There was unanimous agreement that bevacizumab was not a cost-effective front-line therapy compared with platinum-taxane combination for the overall ovarian cancer population, though its use in the high-use population may yield better value. For second-line treatment, platinum-based chemotherapy remained cost-effective among patients with recurrent platinum-sensitive disease, while there was limited evidence to conclude the most valuable treatment alternative among patients with recurrent platinum-resistant disease. Future research incorporating real-world data is essential to corroborate findings from trial-based economic evaluations. In addition, for improving consistency in reporting and quality of studies, incorporating QALYs in this population is important, especially since chemotherapy is administered for lengthy periods of time.

Comparison of the accuracy of Hybrid Capture II and polymerase chain reaction in detecting clinically important cervical dysplasia: a systematic review and meta-analysis.

The effectiveness of screening programs for cervical cancer has benefited from the inclusion of Human papillomavirus (HPV) DNA assays; which assay to choose, however, is not clear based on previous reviews. Our review addressed test accuracy of Hybrid Capture II (HCII) and polymerase chain reaction (PCR) assays based on studies with stronger designs and with more clinically relevant outcomes. We searched OvidMedline, PubMed, and the Cochrane Library for English language studies comparing both tests, published 1985-2012, with cervical dysplasia defined by the Bethesda classification. Meta-analysis provided pooled sensitivity, specificity, and 95% confidence intervals (CIs); meta-regression identified sources of heterogeneity. From 29 reports, we found that the pooled sensitivity and specificity to detect high-grade squamous intraepithelial lesion (HSIL) was higher for HCII than PCR (0.89 [CI: 0.89-0.90] and 0.85 [CI: 0.84-0.86] vs. 0.73 [CI: 0.73-0.74] and 0.62 [CI: 0.62-0.64]). Both assays had higher accuracy to detect cervical dysplasia in Europe than in Asia-Pacific or North America (diagnostic odd ratio - dOR = 4.08 [CI: 1.39-11.91] and 4.56 [CI: 1.86-11.17] for HCII vs. 2.66 [CI: 1.16-6.53] and 3.78 [CI: 1.50-9.51] for PCR) and accuracy to detect HSIL than atypical squamous cells of undetermined significance (ASCUS)/ low-grade squamous intraepithelial lesion (LSIL) (HCII-dOR = 9.04 [CI: 4.12-19.86] and PCR-dOR = 5.60 [CI: 2.87-10.94]). For HCII, using histology as a gold standard results in higher accuracy than using cytology (dOR = 2.87 [CI: 1.31-6.29]). Based on higher test accuracy, our results support the use of HCII in cervical cancer screening programs. The role of HPV type distribution should be explored to determine the worldwide comparability of HPV test accuracy.

Canine rabies vaccination and domestic dog population characteristics in the developing world: a systematic review.

BACKGROUND: Human rabies remains a significant problem in many developing countries, where canine rabies is the most common means of transmission. Although vaccination of dogs has been shown to be the most effective method of prevention in humans, dog vaccination is often lacking. METHODS: This systematic review examined dog rabies vaccination coverage achieved following mass vaccination campaigns and dog ecology/management factors relevant to rabies control in the developing world. We searched a variety of electronic databases for published articles pertaining to dog rabies vaccination or dog ecology where data were collected utilizing a household cluster survey. We reviewed studies published between January 1, 1980 and present and identified 29 articles for inclusion. RESULTS: We found the majority of vaccination campaigns were able to achieve the WHO recommended vaccination coverage of ≥ 70% and calculated weighted mean post-campaign vaccination coverage of 76.5% in urban areas and 73.7% in rural areas. However, we found an absence of studies related to dog vaccination/dog ecology from countries with the greatest burden of rabies such as India, China, and Pakistan. In addition, the majority of dogs in the developing world are very young and short-lived, reducing the effectiveness of vaccination campaigns. CONCLUSIONS: Future studies on canine ecology should be undertaken in countries with high endemic canine rabies. New methods for improving the longevity of dogs and reducing high dog population turnover need to be investigated. Programs which encourage good dog management and promote responsible pet ownership are essential to eliminating canine and human rabies.