Medical Education - Research Publications
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Predicting Infection Risk in Multiple Sclerosis Patients Treated with Ocrelizumab: A Retrospective Cohort Study
(ADIS INT LTD, 2021-04-13)
BACKGROUND: Ocrelizumab safety outcomes have been well evaluated in clinical trials and open-label extension (OLE) studies. However, risk factors for infection in patients with multiple sclerosis (MS) receiving ocrelizumab have not been extensively studied in the real-world setting. OBJECTIVE: The aim of this study was to examine factors determining risk of self-reported infections and antimicrobial use in patients receiving ocrelizumab for MS. METHODS: A retrospective, observational cohort study was conducted in patients receiving ocrelizumab at the Royal Melbourne Hospital. Infection type and number were reported by patients, and the associations of potential clinical and laboratory risk factors with self-reported infection and antimicrobial use were estimated using univariate and multivariable logistic regression models. RESULTS: A total of 185 patients were included in the study; a total of 176 infections were reported in 89 patients (46.1%), and antimicrobial use was identified in 47 patients (25.3%). In univariate analyses, a higher serum IgA was associated with reduced odds of infection (OR 0.44, 95% CI 0.25-0.76). In multivariable analyses, older age (OR 0.94, 95% CI 0.88-0.99), higher serum IgA (OR 0.37, 95% CI 0.17-0.80) and higher serum IgG (OR 0.81, 95% CI 0.67-0.99) were associated with reduced odds of infection. Older age (OR 0.85, 95% CI 0.75-0.96) and higher serum IgA (OR 0.23, 95% CI 0.07-0.79) were associated with reduced odds of antimicrobial use, whilst longer MS disease duration (OR 1.22, 95% CI 1.06-1.41) and higher Expanded Disability Status Scale (EDSS) score (OR 1.99, 95% CI 1.02-3.86) were associated with increased odds of antimicrobial use. CONCLUSIONS: Higher serum IgA and IgG and older age were associated with reduced odds of infection. Our findings highlight that infection risk is not uniform in patients with MS receiving ocrelizumab and substantiate the need to monitor immunoglobulin levels pre-treatment and whilst on therapy.
A designathon to co-create community-driven HIV self-testing services for Nigerian youth: findings from a participatory event
BACKGROUND: Youth are at high risk for HIV, but are often left out of designing interventions, including those focused on adolescents. We organized a designathon for Nigerian youth to develop HIV self-testing (HIVST) strategies for potential implementation in their local communities. A designathon is a problem-focused event where participants work together over a short period to create and present solutions to a judging panel. METHODS: We organized a 72-h designathon for youth (14-24 years old) in Nigeria to design strategies to increase youth HIVST uptake. Proposals included details about HIVST kit service delivery, method of distribution, promotional strategy, and youth audience. Teams pitched their proposals to a diverse seven-member judging panel who scored proposals based on desirability, feasibility, potential impact and teamwork. We examined participants' socio-demographic characteristics and summarized themes from their HIVST proposals. RESULTS: Forty-two youth on 13 teams participated in the designathon. The median team size was 3 participants (IQR: 2-4). The median age was 22.5 years (IQR: 21-24), 66.7% were male, 47.4% completed tertiary education, and 50% lived in Lagos State. Themes from proposals included HIVST integration with other health services, digital marketing and distribution approaches, and engaging students. Judges identified seven teams with exceptional HIVST proposals and five teams were supported for further training. CONCLUSIONS: The designathon provided a structured method for incorporating youth ideas into HIV service delivery. This approach could differentiate HIV services to be more youth-friendly in Nigeria and other settings.
Social network distribution of syphilis self-testing among men who have sex with men in China: study protocol for a cluster randomized control trial
BACKGROUND: Syphilis is a common sexually transmitted infection (STI) among men who have sex with men (MSM). Increasing syphilis testing is important to syphilis control. However, in low- and middle-income countries like China, syphilis testing rates remain low among MSM. We describe a randomized controlled trial protocol to examine the effectiveness of social network distribution approaches of syphilis self-testing among MSM in China. METHODS: We will recruit index and alter MSM. Indexes will be eligible if they: are born biologically male; aged 18 years or above; ever had sex with another man; are willing to distribute syphilis testing packages or referral links to their alters; and willing to provide personal contact information for future follow-up. Three hundred MSM will be recruited and randomly assigned in a 1:1:1 ratio into three arms: standard of care (control arm); standard syphilis self-testing (SST) delivery arm; and referral link SST delivery arm. Indexes will distribute SST packages or referral links to encourage alters to receive syphilis testing. All indexes will complete a baseline survey and a 3-month follow-up survey. Syphilis self-test results will be determined by photo verification via a digital platform. The primary outcome is the mean number of alters who returned verified syphilis testing results per index in each arm. DISCUSSION: The trial findings will provide practical implications in strengthening syphilis self-testing distribution and increasing syphilis testing uptake among MSM in China. This study also empowers MSM community in expanding syphilis testing by using their own social network. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000036988 . Registered 26 August 2020 - Retrospectively registered.
HIV self-testing partially filled the HIV testing gap among men who have sex with men in China during the COVID-19 pandemic: results from an online survey
(JOHN WILEY & SONS LTD, 2021-05-01)
INTRODUCTION: HIV self-testing (HIVST) is a useful strategy to promote HIV testing among key populations. This study aimed to understand HIV testing behaviours among men who have sex with men (MSM) and specifically how HIVST was used during the coronavirus disease 2019 (COVID-19) measures in China when access to facility-based testing was limited. METHODS: An online cross-sectional study was conducted to recruit men who have sex with men (MSM) in China from May to June of 2020, a period when COVID-19 measures were easing. Data on socio-demographic characteristics, sexual behaviours and HIV testing in the three months before and during COVID-19 measures (23 January 2020) were collected. Chi-square test and logistic regression were used for analyses. RESULTS: Overall, 685 MSM were recruited from 135 cities in 30 provinces of China, whose mean age was 28.8 (SD: 6.9) years old. The majority of participants self-identified as gay (81.9%) and had disclosed their sexual orientation (66.7%). In the last three months, 69.6% ever had sex with men, nearly half of whom had multiple sexual partners (47.2%). Although the overall HIV testing rates before and during COVID-19 measures were comparable, more MSM self-tested for HIV during COVID-19 measures (52.1%) compared to before COVID-19 measures (41.6%, p = 0.038). Fewer MSM used facility-based HIV testing during COVID-19 measures (42.9%) compared to before COVID-19 measures (54.1%, p = 0.038). Among 138 facility-based testers before COVID-19 measures, 59.4% stopped facility-based testing during COVID-19 measures. Among 136 self-testers during COVID-19 measures, 58.1% had no HIV self-testing before COVID-19 measures. Multivariable logistic regression showed that having sex with other men in the last three months (adjusted odds ratio, aOR = 2.04, 95% CI: 1.38 to 3.03), self-identifying as gay (aOR = 2.03, 95% CI: 1.31 to 3.13), ever disclosing their sexual orientation (aOR = 1.72, 95% CI: 1.19 to 2.50) and tested for HIV in three months before COVID-19 measures (aOR = 4.74, 95% CI: 3.35 to 6.70) were associated with HIV testing during COVID-19 measures. CONCLUSIONS: Facility-based HIV testing decreased and HIVST increased among MSM during COVID-19 measures in China. MSM successfully accessed HIVST as substitute for facility-based testing, with no overall decrease in HIV testing rates.
Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study
(PUBLIC LIBRARY SCIENCE, 2021-05-01)
BACKGROUND: In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study. METHODS AND FINDINGS: We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient's tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients' tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/- adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing. CONCLUSIONS: We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM. TRIAL REGISTRATION: ACTRN12612000345886.
Appropriate Tourniquet Types in the Pediatric Population: A Systematic Review
(CUREUS INC, 2021-04-13)
Trauma is the leading cause of mortality in those aged 1-19, with hemorrhage accounting for up to 40% of all trauma deaths. Manufactured tourniquets are recommended for the control of life-threatening extremity hemorrhage in adults but their use in the pediatric population requires further investigation. We performed a systematic review to evaluate the most appropriate tourniquet design for use in the pediatric population. A literature search of Embase and the Cochran databases of trials and systematic reviews on October 1, 2020 identified 454 unique references, of which 15 were included for full-text screening. Two single-arm observational studies with a high risk of bias evaluated the use of windlass tourniquets in the pediatric population (73 patients, age 2-16 years). The certainty of the evidence was very low. In both studies, conducted on uninjured extremities, the use of a manufactured windlass tourniquet, specifically the Combat Application Tourniquet (C-A-T®) Generation 7, led to the cessation of Doppler detected pulses in 71/71 (100%) of upper extremities and 69/73 (94.5%) of lower extremities. Of the four failures, one participant withdrew due to pain and three tourniquet applications failed to occlude pulses after three turns of the windlass. No controls were used for comparison. In conclusion, two observational studies demonstrated that windlass tourniquets were able to abolish distal pulses in children as young as two years of age and with a minimum limb circumference of 13 cm. These preliminary findings may be helpful for organizations in the creation of guidelines for the management of life-threatening extremity bleeding in children.
Implementation of an organ space infection prevention bundle reduces the rate of organ space infection after elective colorectal surgery.
BACKGROUND: Surgical site infections (SSIs) are morbid and costly complications after elective colorectal surgery. SSI prevention bundles have been shown to reduce SSI in colorectal surgery, but their impact on organ space infections (OSI) is variable. Adoption of an evidence-based practice without an implementation strategy is often unsuccessful. Our aim was to successfully implement an OSI prevention bundle and to achieve a cost-effective reduction in OSI following elective left-sided colorectal operations. METHODS: The Translating Research into Practice model was used to implement an OSI prevention bundle in all patients undergoing elective left-sided colorectal resections by a single unit from November 2018 to September 2019. The new components included oral antibiotics with mechanical bowel preparation, when required, and use of impermeable surgical gowns. Other standardised components included alcoholic chlorhexidine skin preparation, glove change after bowel handling prior to wound closure with clean instruments. The primary outcome was OSI. Secondary outcomes included bundle compliance, unintended consequences and total patient costs. Outcomes were compared with all patients undergoing elective left-sided colorectal resections at the same institution in 2017. RESULTS: Elective colorectal resections were performed in 173 patients across two cohorts. The compliance rate with bundle items was 63% for all items and 93% for one omitted item. There was a reduction in OSI from 12.9% (11 of 85) to 3.4% (3 of 88, p<0.05) after implementation of the OSI prevention bundle. The average cost of an OSI was $A36 900. The estimated savings for preventing eight OSIs by using the OSI bundle in the second cohort was $A295 198. CONCLUSION: Successful implementation of an OSI prevention bundle was associated with a reduced rate of OSI after elective colorectal surgery. The OSI bundle and its implementation were cost-effective. Further study is required to investigate the sustainability of the OSI prevention bundle.
De-Sexualizing Partner Notification: A Qualitative Study on Chinese Young Adults with Chlamydia
BACKGROUND: Chlamydia is common amongst the sexually active population in Hong Kong. As most cases are asymptomatic, partner notification may be helpful in controlling chlamydia. This study examined attitudes towards partner notification for chlamydia among Hong Kong Chinese youths in order to inform a culturally appropriate, patient-empowering sexual health service. METHODS: Sixteen individuals (aged 20 to 31) who received a confirmed diagnosis of chlamydia within the previous twelve months of data collection were recruited from two community-based organizations between June and December 2017. Semi-structured individual interviews were conducted by a health psychologist. RESULTS: Nine participants notified a total of eleven current and ex-partners. Seven participants did not notify their sexual partner(s). Our findings revealed how participants struggled with the discrediting sexual aspect of their infection, and how de-sexualizing the infection and selected disclosure facilitated partner notification and social acceptance. Perceived stigma regarding chlamydia however did not dissipate with their disclosure. Participants did not perceive lasting impact of chlamydia on their well-being as they thought they have much control over whether and how to disclose to their (future) partners. All participants agreed there was a pressing need to raise public awareness on this silent but highly prevalent sexually transmitted infection. CONCLUSIONS: Our findings illustrate the complex struggle behind communicating about chlamydia to one's sexual partner and how strategizing the disclosure process served to circumvent embarrassment and foster testing of sexual partners.
The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China
(JOHN WILEY & SONS LTD, 2021-04-01)
INTRODUCTION: The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China, over a one- and five-year time horizon. METHODS: Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6-month disruption periods, starting from 1 January 2020. RESULTS: Our model predicted new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions (25% virally suppressed MSM stop taking ART) for a three-month period increasing HIV infections by 5% to 14% over one year and deaths by 7% to 12%. Observed reductions in condom use increased HIV infections by 5% to 14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility HIV testing and ART initiation, but reduced partner numbers resulted in 11% to 23% fewer infections and 0.4% to 1.0% fewer deaths. Longer disruption periods (4/6 months) amplified the impact of disruption scenarios. When realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections occurred over one year (3% to 17%), but not for five years (1% increase to 4% decrease), whereas deaths mostly increased over one year (1% to 2%) and five years (1.2 increase to 0.3 decrease). CONCLUSIONS: The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19-related disruption on HIV transmission and control among MSM in China.
Impact of screening on the prevalence and incidence of Mycoplasma genitalium and its macrolide resistance in men who have sex with men living in Australia: A mathematical model
Background: Mycoplasma genitalium (MG) causes a sexually transmitted infection (STI) with a rising rate of antimicrobial resistance. Currently, guidelines do not recommend screening asymptomatic men who have sex with men (MSM). We developed a mathematical model of MG transmission to examine the impact of various screening strategies on the incidence and prevalence of MG among MSM attending a sexual health clinic. Methods: A compartmental mathematical model of MG transmission among MSM was constructed and calibrated using data from the Melbourne Sexual Health center, where resistance-guided therapy provides high treatment effectiveness (92-95%). The model stratified men by symptom status, sexual risk behaviours and whether or not they had MG with macrolide resistance. We simulated the impact on endemic steady-state MG prevalence and incidence of the following screening scenarios, namely screening: 1) no MSM; 2) only symptomatic MSM (the current recommendation); 3) all symptomatic and high-risk asymptomatic MSM; and 4) all MSM. Our base case analysis assumed a treatment effectiveness of 92-95% using resistance-guided therapy. We also examined the impact of treatment effectiveness (i.e. the proportion of detected MG that were cured) and screening coverage (i.e. testing rate) on MG prevalence. Findings: The model predicts that the overall endemic MG prevalence is 9.1% (95% CI: 7.9-10.0) in the current situation where screening is only offered to symptomatic MSM (base-case). This would increase to 11·4% (95% confidence intervals (CI): 10.2-13.7) if no MSM are offered screening, but would decrease to 7.3% (95% CI: 5.7-8.4) if all symptomatic and high-risk asymptomatic MSM were offered screening and 6.4% (95% CI: 4.7-7·7) if all MSM were offered screening. Increasing coverage of MSM screening strategies shows a similar effect on decreasing endemic MG incidence. When evaluating the simultaneous impact of treatment effectiveness and screening coverage, we found that offering screening to more MSM may reduce the overall prevalence but leads to a higher proportion of macrolide-resistant MG, particularly when using treatment regimens with lower effectiveness. Interpretation: Based on the available treatment options, offering screening for MG to other MSM (beyond the currently recommended group of symptomatic MSM) could slightly reduce the prevalence and incidence of MG. However, further increasing screening coverage must be weighed against the impact of lower treatment effectiveness (i.e. when not using resistance-guided therapy), increasing the selection of macrolide resistance, and other negative consequences related to AMR and management (e.g. unnecessary psychological morbidity from infections that do not need treatment).
HIV incidence among men who have sex with men using geosocial networking smartphone application in Beijing, China: an open cohort study
BACKGROUND: Sexual transmission among men who have sex with men (MSM) is the dominant route of HIV transmission in China. Extensive use of geosocial networking (GSN) smartphone application (app) has dramatically changed the pattern of sexual behaviors and HIV risk among MSM, but data on HIV incidence and the changing risk behaviors of GSN app-using MSM are limited. We aims to assess the HIV incidence and its correlates among gay GSN app-using MSM in China. METHODS: We constructed an open cohort which was initiated and maintained using a GSN app to assess the HIV incidence among app-using MSM, recruited from June 2017 to December 2018. MSM completed an online questionnaire on their sociodemographic characteristics, sexual behaviors, recreational drug use and sexually transmitted infections status. Then each man had an HIV test, and those tested negatives were enrolled into the cohort. Participants completed follow-ups with additional HIV tests though the app during the study period, and were censored at HIV seroconversion or study end date. HIV incidence was calculated by dividing the sum of observed HIV seroconversions by the observed person-time. Univariate (Chi-square test and Fisher's exact test) and multivariate (proportional hazards regression) analyses were used to examine correlates of HIV incidence. RESULTS: A total of 6957 HIV negative MSM were enrolled in the open cohort, 37 seroconversions occurred among 1937 men contributing 1065 observed person-years: HIV incidence was 3.47 per 100 person-years [95% confidence interval (CI): 2.37-4.57]. More than five sexual partners [hazard ratio (HR) = 2.65, 95% CI: 1.04-6.67], and sex with HIV positive partners (HR = 3.82, 95% CI: 1.16-12.64) in the preceding six months were positively associated with HIV seroconversion. Consistent condom use for anal sex (HR = 0.27, 95% CI: 0.07-0.96), and reporting insertive anal sex only (HR = 0.23, 95% CI: 0.08-0.62) in the preceding six months were protective factors for HIV seroconversion. CONCLUSIONS: Tailored interventions targeting app-using MSM are urgently needed given their high risk of HIV. As a new tool for accessing MSM at higher HIV risk, GSN smartphone app could play an important role in HIV research among MSM.