Comprehensive profiling of social mixing patterns in resource poor countries: A mixed methods research protocol.

BACKGROUND: Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling. METHODS: To address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures. We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants' interactions with household members using high resolution data from the proximity sensors and calculating infants' proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member. DISCUSSION: Our qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies.

Preoperative Cervical Epidural Steroid Injections: Utilization and Postoperative Complications in ACDF, PCDF, and Decompression.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Identify factors associated with cervical epidural steroid injection (CESI) receipt before anterior cervical discectomy and fusion (ACDF), posterior cervical decompression and fusion (PCDF), or decompression; evaluate the association between CESI receipt and 90-day postoperative complications; and determine characteristics of CESI associated with complications. SUMMARY OF BACKGROUND DATA: Previous literature has suggested that a preoperative CESI may increase the risk of postoperative complications. However, these studies were limited in the procedures and complications they evaluated. METHODS: The IBM MarketScan database was queried for patients aged 18 years or older who underwent ACDF, PCDF, or cervical decompression for disc herniation, stenosis, radiculopathy, myelopathy, and/or spondylosis without myelopathy between January 1, 2014 and September 30, 2020. CESI receipt within 12 months preoperatively, injection characteristics, and postoperative complications were extracted. Multivariable logistic regression models were used to investigate associations between patient characteristics and receipt of CESI, receipt of a CESI and each 90-day postoperative complication, and CESI characteristics and each 90-day complication. RESULTS: Among the unique patients who underwent each procedure, 20,371 ACDF patients (30.93%), 1259 (22.24%) PCDF patients, and 3349 (36.30%) decompression patients received a preoperative CESI. In all 3 cohorts, increasing age, increasing comorbidity burden, smoker status, and diagnosis of myelopathy were associated with decreased odds of preoperative CESI receipt, while female sex and diagnosis of radiculopathy and spondylosis without myelopathy were associated with increased odds. There were no meaningful between-group comparisons or significant associations between preoperative CESI receipt and any 90-day postoperative complications in multivariable models (all P>0.05). CONCLUSIONS: This study elucidated the main determinants of CESI receipt and found no differences in the odds of developing 90-day postoperative complications, but did identify differential outcomes with regard to some injection characteristics. LEVEL OF EVIDENCE: Level III.

Vaccine effectiveness of 3rd generation mpox vaccines against mpox and disease severity: A systematic review and meta-analysis.

INTRODUCTION: Before the global mpox outbreak which began in 2022, the real-world vaccine effectiveness (VE) of mpox vaccines was unknown. We quantified the VE in the global population of 3rd generation or later mpox vaccines (MVA-BN, LC16m8, OrthopoxVac) compared with unvaccinated or other vaccinated states for infection, hospitalization and death. VE was stratified by 1-dose and 2-doses and post-exposure prophylaxis (PEP). METHODS: Studies were included if they measured vaccine efficacy or effectiveness in humans. Animal studies and immunogenicity studies were excluded. MEDLINE, Web of Science, Google Scholar, Embase, MedRxiv and grey literature were searched from January 1st, 1970, with the last search run on November 3, 2023 (Prospero, CRD42022345240). Risk of publication bias was assessed via funnel plots and Egger's test, and study quality via Newcastle-Ottawa scales. RESULTS: A total of 11,892 records were identified via primary search, 3,223 via citation chasing. Thirty-three studies were identified of 3rd generation vaccines, 32 of which were MVA-BN. Two additional studies were re-analysis of existing data. Most of these studies were focused on gay, bisexual, or other men who have sex with men between the ages of 18-49 in May to October of 2022. VE of 1 dose of MVA-BN was 76% (95%CI 64-88%) from twelve studies. VE of 2 doses was 82% (95%CI 72-92%) from six studies. VE of MVA-BN PEP against mpox was 20% (95%CI -24-65%) from seven studies. All VE are calculated from random effects estimates. 18/33(55%) studies were rated as poor, 3/33(9%) as fair and 12/33(36%) as good. Studies included in the meta-analysis had higher quality: 11/16 (69%) were rated as good quality. CONCLUSION: Both 1 and 2 doses of MVA-BN are highly effective at preventing mpox. Effectiveness estimates, specifically of PEP are limited by immortal time bias, predominant mode of mpox transmission, and real-world vaccine timing of administration.

Prescribing Justice: A Close Examination of Physicians Acting As Expert Witnesses in Saudi Arabia.

INTRODUCTION: An expert witness is a person who provides testimony on issues that the court finds to be outside the scope of their expertise and experience. Any physician who has performed an independent medical evaluation or written medical records can and should expect to be requested as an expert witness. Medical malpractice, workers' compensation, and personal injury are the most prominent areas where medical expert witnesses participate and provide opinions and testimony. To our knowledge, this is the first study to be conducted in Saudi Arabia on physicians acting as expert witnesses. METHODS: This observational descriptive cross-sectional study conducted in Saudi Arabia from November 2022 to July 2023 aimed to assess physicians' experiences, education, training, willingness, self-competency, attitude, and perception as expert witnesses. The study population consisted of physicians working in Saudi Arabia, with at least a specialist level of professional expertise. Participants completed a self-administered online survey, utilizing a researcher-designed questionnaire. RESULTS: In total, 417 participants, with males comprising 51.3% of the sample, responded to the survey. More than half of the physicians (58.3%) had never produced a medical report for the court. Among those who had, the majority had done so one to twice. Similarly, the majority had never testified in court (77.5%), with only a small percentage having done so once or twice. Approximately 80% of participants had no prior education or training as expert witnesses, but among those who did, courses and workshops were the most common forms of education or training. Most participants expressed interest in learning or training for this role (69.1%) and were willing to provide medical reports or court testimony (73.9%). However, half of the participants did not feel competent in writing a medical report for the court, and more than half lacked confidence in giving testimony. CONCLUSION: The findings highlight the need for increased engagement, education, and training among physicians, particularly early and mid-career professionals, to enhance their confidence and competence as expert witnesses and ensure ethical practices in the medicolegal domain in Saudi Arabia.

Crafting Tomorrow's Medical Leaders: Insights from Medical Students and Interns in Saudi Arabia.

Introduction: Leadership is increasingly recognized as a crucial competency in medicine, with physicians expected to provide leadership skills throughout their careers. This study explores the perceptions, attitudes, and interests of medical students and interns in Saudi Arabia regarding medical leadership. Medical graduates are expected to "provide leadership skills that enhance team functioning, the learning environment, and the healthcare delivery system", according to the Association of American Medical Colleges (AAMC). Methods: A cross-sectional study was conducted from January to July 2023, involving 519 medical students and interns in Saudi Arabia. An online survey covered demographic data, perceptions, attitudes, interests, and self-perceived leadership skills. A pilot study was conducted to ensure the questionnaire's validity and reliability. Data were analyzed using SPSS 26, employing descriptive statistics and inferential tests. Results: Most participants had a positive perception of leadership (38.3%), with higher scores associated with medical specialties as a career choice (p < 0.001). The majority expressed average interest in medical leadership (29.1%). Communication and organizational skills were highly self-rated leadership attributes. Barriers to leadership implementation included lack of interest (49.3%), inadequate training (45.1%), and time constraints (43.2%). Only 14.6% rated leadership education in medical school as "very good". Conclusion: This study underscores the importance of leadership in medical education. Integrating comprehensive and structured leadership programs into medical curricula, addressing barriers, and promoting awareness can foster future medical leaders. Continuous evaluation and adaptation are essential for ensuring the relevance and effectiveness of leadership training.

Does Medicare Insurance Mitigate Racial/Ethnic Disparities in Access to Lumbar Spinal Surgery When Compared to Commercial Insurance?

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Compare disparities in lumbar surgical care utilization in Commercially insured versus Medicare patients. SUMMARY OF BACKGROUND DATA: While disparities in spinal surgery have been previously described, less evidence exists on effective strategies to mitigate them. Theoretically, universal health care coverage under Medicare should improve health care access. MATERIALS AND METHODS: Utilizing National Inpatient Sample data (2003-2018), we included inpatient lumbar discectomy or laminectomy/fusion cases in black, white, or Hispanic patients aged 18-74 years, with Commercial or Medicare insurance. A multivariable Poisson distribution model determined race/ethnicity subgroup-specific rate ratios (RRs) of patients undergoing lumbar surgery compared to their respective population distribution (using US Census data) based on race/ethnicity, region, gender, primary payor, and age (Commercially insured age subgroups: 18-39, 40-54, and 55-64 y; Medicare age subgroup: 65-74 y). RESULTS: Of the 2,310,956 lumbar spine procedures included, 88.9%, 6.1%, and 5.0% represented white, black, and Hispanic patients, respectively. Among Commercially insured patients, black and Hispanic (compared to white) patients had lower rates of surgical care utilization; however, these disparities decreased with increasing age: black (RR=0.37, 95% CI: 0.37-0.38) and Hispanic patients (RR=0.53, 95% CI: 0.52-0.54) aged 18-39 years versus black (RR=0.72, 95% CI: 0.71-0.73) and Hispanic patients (RR=0.64, 95% CI: 0.63-0.65) aged 55-64 years. Racial/ethnic disparities persisted in Medicare patients, especially when compared to the neighboring age subgroup that was Commercially insured: black (RR=0.61, 95% CI: 0.60-0.62) and Hispanic patients (RR=0.61, 95% CI: 0.60-0.61) under Medicare. CONCLUSIONS: Disparities in surgical care utilization among black and Hispanic patients persist regardless of health care coverage, and an expansion of Medicare eligibility alone may not comprehensively address health care disparities. LEVEL OF EVIDENCE: Level III.

Environmental surveillance for COVID-19 using SARS-CoV-2 RNA concentration in wastewater - a study in District East, Karachi, Pakistan.

Background: Wastewater-based surveillance is used to track the temporal patterns of the SARS-CoV-2 virus in communities. Viral RNA particle detection in wastewater samples can indicate an outbreak within a catchment area. We describe the feasibility of using a sewage network to monitor SARS-CoV-2 trend and use of genomic sequencing to describe the viral variant abundance in an urban district in Karachi, Pakistan. This was among the first studies from Pakistan to demonstrate the surveillance for SARS-CoV-2 from a semi-formal sewage system. Methods: Four sites draining into the Lyari River in District East, Karachi, were identified and included in the current study. Raw sewage samples were collected early morning twice weekly from each site between June 10, 2021 and January 17, 2022, using Bag Mediated Filtration System (BMFS). Secondary concentration of filtered samples was achieved by ultracentrifugation and skim milk flocculation. SARS-CoV-2 RNA concentrations in the samples were estimated using PCR (Qiagen ProMega kits for N1 & N2 genes). A distributed-lag negative binomial regression model within a hierarchical Bayesian framework was used to describe the relationship between wastewater RNA concentration and COVID-19 cases from the catchment area. Genomic sequencing was performed using Illumina iSeq100. Findings: Among the 151 raw sewage samples included in the study, 123 samples (81.5%) tested positive for N1 or N2 genes. The average SARS-CoV-2 RNA concentrations in the sewage samples at each lag (1-14 days prior) were associated with the cases reported for the respective days, with a peak association observed on lag day 10 (RR: 1.15; 95% Credible Interval: 1.10-1.21). Genomic sequencing showed that the delta variant dominated till September 2022, while the omicron variant was identified in November 2022. Interpretation: Wastewater-based surveillance, together with genomic sequencing provides valuable information for monitoring the community temporal trend of SARS-CoV-2. Funding: PATH, Bill & Melinda Gates Foundation, and Global Innovation Fund.

Incorporating Efficacy Data from Initial Trials Into Subsequent Evaluations: Application to Vaccines Against Respiratory Syncytial Virus.

BACKGROUND: When a randomized controlled trial fails to demonstrate statistically significant efficacy against the primary endpoint, a potentially costly new trial would need to be conducted to receive licensure. Incorporating data from previous trials might allow for more efficient follow-up trials to demonstrate efficacy, speeding the availability of effective vaccines. METHODS: Based on the outcomes from a failed trial of a maternal vaccine against respiratory syncytial virus (RSV), we simulated data for a new Bayesian group-sequential trial. We analyzed the data either ignoring data from the previous trial (i.e., weakly informative prior distributions) or using prior distributions incorporating the historical data into the analysis. We evaluated scenarios where efficacy in the new trial was the same, greater than, or less than that in the original trial. For each scenario, we evaluated the statistical power and type I error rate for estimating the vaccine effect following interim analyses. RESULTS: When we used a stringent threshold to control the type I error rate, analyses incorporating historical data had a small advantage over trials that did not. If control of type I error is less important (e.g., in a postlicensure evaluation), the incorporation of historical data can provide a substantial boost in efficiency. CONCLUSIONS: Due to the need to control the type I error rate in trials used to license a vaccine, incorporating historical data provides little additional benefit in terms of stopping the trial early. However, these statistical approaches could be promising in evaluations that use real-world evidence following licensure.

Nirmatrelvir/Ritonavir Use and Hospitalizations or Death in a Previously Uninfected Nonhospitalized High-Risk Population With COVID-19: A Matched Cohort Study.

OBJECTIVE: To determine the association of nirmatrelvir/ritonavir (NMV/r) with hospitalization or death within 30 days as compared with untreated controls previously uninfected and nonhospitalized. METHODS: We used a matched cohort design using inverse probability of treatment weight (IPTW). Individuals prescribed NMV/r within 3 days of COVID-19 diagnosis were compared with IPTW-based untreated controls. Variables for IPTW included age, race, sex, body mass index, geographic location, vaccination status, and multiple comorbidities. Additional analyses were conducted on NMV/r-treated and propensity score-matched untreated controls. RESULTS: Among 7615 individuals prescribed NMV/r and 62 077 controls identified between 1 January 2022 and 25 February 2023, the risk of hospitalization/death was lower among NMV/r-treated persons vs untreated controls (243 vs 3468 events; absolute risk difference [ARD], -2.36 [95% CI, -2.57 to -2.14]). The difference was significant for those >60 and ≤60 years old (ARD, -3.86 [95% CI, -4.19 to -3.54] vs -0.27 [95% CI, -0.51 to -0.03]) and for persons asymptomatic and symptomatic (ARD, -7.09 [95% CI, -7.62 to -6.55] vs -1.46 [95% CI, -1.66 to -1.25]). Significant benefit was observed among individuals unvaccinated and vaccinated, with or without a booster dose. CONCLUSIONS: NMV/r is associated with a significant reduction in 30-day hospitalization or death among individuals previously uninfected and nonhospitalized.

Postmortem minimally invasive tissue sampling in communities: exploring perceptions of families, funeral workers, religious and community leaders and healthcare providers from Pakistan.

BACKGROUND: Minimally invasive tissue sampling (MITS) has increasingly been used to improve the diagnosis of disease and identification of the cause of death, particularly in underserved areas. However, there are multiple barriers to accessing those who die within the community, our study aimed to explore the perceptions and insights of community members and healthcare providers regarding the feasibility of implementing MITS in community settings. METHODS: A qualitative exploratory study was conducted. A total of twenty one in-depth interviews were conducted with deceased infants' parents, elders of the family, religious leaders, community leaders, and funeral workers. Focus group discussions were conducted with health care providers (n = 14) in two peri-urban slum areas of Karachi, Pakistan. The duration of this study was from August to October 2020. Data was analyzed using thematic analysis and was coded and merged into categories forming eight major themes. RESULTS: In general, participants viewed minimally invasive tissue sampling (MITS) as beneficial for improving child health, though some had concerns about disrespecting the deceased during sample collection. Misinformation, fear of needles, and medical procedures were major barriers to MITS implementation. To enhance acceptance, community and religious leaders suggested using religious rulings, obtaining parental consent, ensuring confidentiality, and increasing efforts of community engagement. Community healthcare providers, along with funeral workers, recommended providing community members with grief counseling to increase study participation. Besides concerns about sampling interfering with respect for the decease, community members also raised concerns about misinformation. Further, participants provided feedback on the design and appearance of the mobile van used to collect MITS samples from children under the age of five. CONCLUSION: This study is critical for understanding the challenges associated with implementation of community-based MITS sampling in Pakistan. Integrating the use of a mobile van for sample collection, grief counseling along with community engagement sessions and advocacy will help address community-based misinformation and develop community trust.

Comprehensive profiling of social mixing patterns in resource poor countries: a mixed methods research protocol.

Background: Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling. Methods: To address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures.We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants' interactions with household members using high resolution data from the proximity sensors and calculating infants' proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member. Discussion: Our qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies.

Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model.

Background: Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model. Methods: Ten skeletally mature sheep (4-5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1-L2, L2-L3, and L3-L4 lumbar IVDs. L4-L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin-crosslinked fibrin (FibGen), (4) carboxymethylcellulose-methylcellulose (C-MC), or (5) C-MC and FibGen (FibGen + C-MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology. Results: All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C-MC) and combination repair (i.e., FibGen + C-MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C-MC showed signs of herniation via biomaterial expulsion. Conclusions: All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C-MC and FibGen + C-MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury-induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.

Changing social contact patterns among US workers during the COVID-19 pandemic: April 2020 to December 2021.

Non-pharmaceutical interventions minimize social contacts, hence the spread of respiratory pathogens such as influenza and SARS-CoV-2. Globally, there is a paucity of social contact data from the workforce. In this study, we quantified two-day contact patterns among USA employees. Contacts were defined as face-to-face conversations, involving physical touch or proximity to another individual and were collected using electronic self-kept diaries. Data were collected over 4 rounds from 2020 to 2021 during the COVID-19 pandemic. Mean (standard deviation) contacts reported by 1456 participants were 2.5 (2.5), 8.2 (7.1), 9.2 (7.1) and 10.1 (9.5) across round 1 (April-June 2020), 2 (November 2020-January 2021), 3 (June-August 2021), and 4 (November-December 2021), respectively. Between round 1 and 2, we report a 3-fold increase in the mean number of contacts reported per participant with no major increases from round 2-4. We then modeled SARS-CoV-2 transmission at home, work, and community settings. The model revealed reduced relative transmission in all settings in round 1. Subsequently, transmission increased at home and in the community but remained exceptionally low in work settings. To accurately parameterize models of infection transmission and control, we need empirical social contact data that capture human mixing behavior across time.

Social contact patterns among employees in U.S. long-term care facilities during the COVID-19 pandemic, December 2020 to June 2021.

OBJECTIVE: We measured contact patterns using social contact diaries for 157 U.S. long-term care facility employees from December 2020 - June 2021. These data are crucial for analyzing mathematical transmission models and for informing healthcare setting infection control policy. RESULTS: The median number of daily contacts was 10 (IQR 8-11). Household contacts were more likely partially masked than fully masked, more likely to involve physical contact, and longer in duration compared to facility contacts.

Moral foundations and HPV vaccine acceptance in the United States: State, parental, and individual factors.

RATIONALE: Appeals to intuitive morality may present a novel approach to addressing vaccine hesitancy. OBJECTIVE: To better understand the relationship between morality and vaccination by employing Moral Foundations Theory to studies surrounding the HPV vaccination at multiple different levels of decision making. METHOD: We employed three different study modalities which examined moralities link to vaccination by employing Moral Foundations Theory. A state-wide ecological study aimed to understand population level trends. Two randomized control interventional studies were then created to understand the effects of Moral Foundations Theory based interventions on both parents of children and individual decision makers. RESULTS: We demonstrated a negative association at the state level between the purity moral foundations and HPV vaccination rates (ß = -.75, SE 0.23; p < .01) and a positive association between loyalty and HPV vaccination rates (ß = 0.62 SE 0.24; p < .05). The parental study built upon this by demonstrating negative association between higher moral purity scores and attitudes towards the HPV vaccine and intention to vaccinate their children (ß = -0.27 SE 0.07; p < .001). Our final study demonstrated a Moral Foundations Theory based intervention was associated with an increase in the odds of indicating an intention to receive the HPV vaccination (adjusted Odds Ratio (aOR) 2.59, 95% Confidence Interval (CI) 1.62-4.14). This equates to a 20% increase in the predicted probability of the intention to receive an HPV vaccine (39% CI (36%-42%) vs 60% CI (57%-63%). CONCLUSIONS: Together, these studies demonstrate that moral foundations, specifically the purity foundation, appear to have a strong and consistent relationship with HPV vaccination. They also demonstrate the how moral values-based interventions may serve as a novel approach to increase HPV vaccine uptake with potential to be employed to target vaccine hesitancy more broadly.

Kindergarten Vaccination Status in California After Changes to Medical Exemption Policy.

This study evaluates changes in medical exemptions and geographic distribution of kindergarteners in California not up to date on vaccination after changes to state legislation.

Behavioral interventions for vaccination uptake: A systematic review and meta-analysis.

BACKGROUND: Human behavior and more specifically behavioral insight-based approaches to vaccine uptake have often been overlooked. While there have been a few narrative reviews indexed in Medline on behavioral interventions to increase vaccine uptake, to our knowledge, none have been systematic reviews and meta-analyses covering not just high but also low-and-middle income countries. METHODS: We included 613 studies from the Medline database in our systematic review and meta-analysis categorizing different behavioral interventions in 9 domains: education campaigns, on-site vaccination, incentives, free vaccination, institutional recommendation, provider recommendation, reminder and recall, message framing, and vaccine champion. Additionally, considering that there is variability in the acceptance of vaccines among different populations, we assessed studies from both high-income countries (HICs) and low- to middle-income countries (LMICs), separately. FINDINGS: Our results showed that behavioral interventions can considerably improve vaccine uptake in most settings. All domains that we examined improved vaccine uptake with the highest effect size associated with provider recommendation (OR: 3.4 (95%CI: 2.5-4.6); Domain: motivation) and on-site vaccination (OR: 2.9 (95%CI: 2.3-3.7); Domain: practical issues). While the number of studies conducted in LMICs was smaller, the quality of studies was similar with those conducted in HICs. Nevertheless, there were variations in the observed effect sizes. INTERPRETATION: Our findings indicate that "provider recommendation" and "on-site vaccination" along with other behavioral interventions can be employed to increase vaccination rates globally.

Persuasive COVID-19 vaccination campaigns on Facebook and nationwide vaccination coverage in Ukraine, India, and Pakistan.

Social media platforms have a wide and influential reach, and as such provide an opportunity to increase vaccine uptake. To date, there is no large-scale, robust evidence on the offline effects of online messaging campaigns. We aimed to test whether pre-tested, persuasive messaging campaigns from UNICEF, disseminated on Facebook, influenced COVID-19 vaccine uptake in Ukraine, India, and Pakistan. In Ukraine, we deployed a stepped-wedge randomized controlled trial (RCT). Half of the 24 oblasts (provinces) received five weeks of the intervention, the other half ten weeks of the intervention. In India, an RCT with an augmented synthetic control was conducted in five states (Bihar, Chhattisgarh, Jharkhand, Madhya Pradesh, Rajasthan), whereby 40 out of 174 districts were randomized to receive six weeks of intervention. In Pakistan we deployed a pre-post design, whereby 25 city districts received six weeks of the intervention. Weekly COVID-19 vaccination data was sourced through government databases. Using Poisson regression models, the association between the intervention and vaccine uptake was estimated. In Ukraine we conducted a survey among Facebook users at three time points during the RCT, to ascertain vaccination intentions and trust in vaccines. The campaigns reached more than 110 million Facebook users and garnered 2.9 million clicks. In Ukraine, we found that the intervention did not affect oblast-level vaccination coverage (Relative Risk (RR): 0.93, 95% Confidence Interval (CI) 0.86-1.01). Similarly, in India and Pakistan we found no effect of our intervention (India: RR 0.85, 95% CI 0.70-1.04; Pakistan: RR 0.64, 95% CI 0.01-29.9). The survey among Facebook users in Ukraine showed that trust in vaccines and information sources was an important predictor of vaccination status and intention to get vaccinated. Our campaigns on Facebook had a wide reach, which did not translate in shifting behaviours. Timing and external events may have limited the effectiveness of our interventions.

Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

Barriers to research productivity amongst postgraduate trainees: results from a survey of 333 medical and surgical residents.

PURPOSE: We aimed to determine the perceptions of, barriers to, and predictors of research engagement amongst residents at a national level in Pakistan. METHODS: This cross-sectional study used REDCap for online survey dissemination to residents from 12 institutes accredited by the national accreditation body (College of Physicians and Surgeons Pakistan) for core medical and surgical specialties. Logistic regression was used to estimate associations between likelihood of publications and participant characteristics. RESULTS: The response rate was 79% (333/423), with 171 (51%) medical and 162 (49%) surgical residents. The mean ± standard deviation age was 28.8 ± 2.7 years; 137 (41%) were males and 195 (59%) females. More than half the residents, 202 (61%), had received research training, but 189 (57%) scored <33% on basic research knowledge. While most residents agreed on the positive impact of research on their careers (P = .012) and realized that they should be involved in it (P = .33), they also strongly believed that it was difficult to engage in research during training (P < .01). Only 60 (18%) trainees had published a paper in local and 37 (11%) in international journals, respectively. The most significant barriers to conducting research included time limitation due to clinical work, lack of financial support, and unavailability of data (P < .01). CONCLUSION: Residents have a positive attitude towards research. However, research engagement among residents is low. Improving research mentorship and creating systems that enable protected time and institutional access to data are needed to increase research output of postgraduate trainees. Key messages What is already known on this topic Postgraduate trainees benefit academically from research conducted during residency training. However, in low- and middle-income countries like Pakistan, research output among residents has remained low over the years. The nation has consistently produced very little research. What this study adds The current study helped shed light on the reasons for low research productivity amongst medical and surgical residents in Pakistan. How this study might affect research, practice, or policy The potential predictors for low research involvement highlighted in this study necessitate modification of the existing national residency curriculum to increase research engagement and productivity among residents. Not only can the potential factors be improved, but the study also helps in bringing stakeholders' attention to increasing research opportunities in Pakistan.