Viral cultures, cycle threshold values and viral load estimation for assessing SARS-CoV-2 infectiousness in haematopoietic stem cell and solid organ transplant patients: a systematic review.

BACKGROUND: Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant recipients due to immunosuppression, and may pose a continued transmission risk, especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation. OBJECTIVES: To investigate the relationship between serial SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value or cycle of quantification value, or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture, including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship, in transplant recipients. METHODS: LitCovid, medRxiv, Google Scholar and the World Health Organization COVID-19 database were searched from 1st November 2019 to 26th October 2022. Studies reporting relevant data (results from serial RT-PCR testing and viral culture data from the same respiratory samples) for transplant recipients with SARS-CoV-2 infection were included in this systematic review: Methodological quality was assessed using five criteria, and the data were synthesized narratively and graphically. RESULTS: Thirteen case reports and case series reporting on 41 transplant recipients (22 renal, five cardiac, one bone marrow, two liver, one bilateral lung and 10 blood stem cell) were included in this review. A relationship was observed between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for >100 days after symptom onset. Lack of standardization of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplant recipients stopped shedding replication-competent viruses when the Ct value was >30 despite differences across platforms. CONCLUSIONS: Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardized study design and reporting are essential to standardize guidance based on an increasing evidence base.

Viral cultures for assessing fomite transmission of SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: The role of fomites in the transmission of SARS-CoV-2 is unclear. AIM: To assess whether SARS-CoV-2 can be transmitted through fomites, using evidence from viral culture studies. METHODS: Searches were conducted in the World Health Organization COVID-19 Database, PubMed, LitCovid, medRxiv, and Google Scholar to December 31st, 2021. Studies that investigated fomite transmission and performed viral culture to assess the cytopathic effect (CPE) of positive fomite samples and confirmation of SARS-CoV-2 as the cause of the CPE were included. The risk of bias using a checklist modified from the modified Quality Assessment of Diagnostic Accuracy Studies - 2 (QUADAS-2) criteria was assessed. FINDINGS: Twenty-three studies were included. The overall risk of bias was moderate. Five studies demonstrated replication-competent virus from fomite cultures and three used genome sequencing to match fomite samples with human clinical specimens. The mean cycle threshold (CT) of samples with positive viral culture was significantly lower compared with cultured samples that returned negative results (standardized mean difference: -1.45; 95% confidence interval (CI): -2.00 to -0.90; I2 = 0%; P < 0.00001). The likelihood of isolating replication-competent virus was significantly greater when CT was <30 (relative risk: 3.10; 95% CI: 1.32 to 7.31; I2 = 71%; P = 0.01). Infectious specimens were mostly detected within seven days of symptom onset. One study showed possible transmission of SARS-CoV-2 from fomites to humans. CONCLUSION: The evidence from published studies suggests that replication-competent SARS-CoV-2 is present on fomites. Replication-competent SARS-CoV-2 is significantly more likely when the PCR CT for clinical specimens and fomite samples is <30. Further studies should investigate the duration of infectiousness of SARS-CoV-2 and the frequency of transmission from fomites.

Comparison of primary care doctors and dentists in the referral of oral cancer: a systematic review.

Oral cancer is referred to specialists by both general practitioners (GPs) and dentists, with varying proportions reported in different studies. However, some have noted that dentists more commonly refer oral cancer in the absence of patient-perceived symptoms and may refer at an earlier stage. Unfortunately, approximately half the UK adult population do not receive regular dental care. We have conducted a systematic review of studies that compare GPs and dentists in the referral of oral cancer and have focused on three aspects: the proportion of diagnosed oral cancers, stage on presentation, and delay. Searches of the databases Medline, Embase, Scopus, Google Scholar, Web of Science, and CINAHL, together with additional searches of reference lists, authors, and conference proceedings, found 22 studies from 10 countries, which included a total of 4953 oral cancers. The percentage of medical referrals ranged from 13% to 86%; dental referrals ranged from 15% to 80%. Random-effects meta-analysis indicated a combined relative risk of medical referral to dental referral of 1.36 (95% CI: 0.99 to 1.86). For UK-based studies, the relative risk was also 1.36 (95% CI: 1.05 to 1.76). There was considerable heterogeneity for all studies and for a subgroup of UK studies: I296.4% (95% CI 95.4 to 97.1) and 81.0% (95% CI 63.3 to 90.1), respectively. Several studies showed a lower stage for dentally-referred cancers; the combined risk for dentists and GPs referring early (stages 1 and 2) disease was 1.37 (95% CI: 1.17 to 1.60), and one cause may be the much higher number of cases referred by dentists in the absence of symptoms. No studies showed a significant difference in delay. Oral cancer is referred by both GPs and dentists, typically about 50% and 40%, respectively, although there is a wide range, probably depending on local circumstances. Both groups require skills in oral examination, recognition of lesions, and knowledge of the risk factors. Effectively, regular dental attenders are a select group that is regularly screened for oral cancer, and it is likely that screening is not delivered to those with the highest risk. We suggest that further work is required on how to access high-risk individuals both for possible screening and preventive interventions.

Referrals for head and neck cancer in England and The Netherlands: an international qualitative study of the views of secondary-care surgical specialists.

One-year survival after head and neck cancer in England has been reported to be worse than that in Europe, despite five-year conditional survival being similar, which implies that patients present later in England. One country with better rates is The Netherlands. There are many possible causes, one of which may be the system of referral from primary to secondary care. We have compared the views of secondary care specialists in the two countries about their systems for referral, and identified aspects that might have an impact on outcomes. We organised semistructured qualitative interviews of surgical specialists in head and neck cancer in England and The Netherlands (n=12 in each). The most common theme was communication between primary care and specialists. Surgeons in England identified this as the aspect most lacking under the English "two-week" rule, while Dutch specialists felt that the good communication in their system was one of its best points. Other themes included the educational needs of primary care practitioners, criticism of "tick box" referrals in England, and too many patients referred who do not have cancer. Overall, specialists in both countries identified good aspects of their respective referral systems, but those in England felt strongly that the "two-week" rule/NICE guidance system could be improved with better direct communication between primary and secondary care, which might improve the speed and quality of referrals, reduce unnecessary ones, and assist in educating primary care physicians. It is not clear whether such improvements would improve survival, but further research and piloting of such a system should be considered in England.

Decline in adolescent treatment admissions for methamphetamine use in Cape Town.

BACKGROUND AND OBJECTIVES: The purpose of this report is to describe the changing trends in adolescent treatment admissions for methamphetamine in Cape Town, and to discuss possible implications. METHOD: Data were collected on admissions for drug abuse treatment through a regular monitoring system involving drug treatment centres and programmes in Cape Town, every 6 months as part of the South African Community Epidemiology Network on Drug Use (SACENDU). A one-page form was completed by treatment centre personnel for each patient to collect demographic and substance abuse data. RESULTS: The results indicate that between 2004 and 2006, a significant increase in the proportion of adolescent treatment admissions for methamphetamine abuse occurred, while a significant decrease occurred between 2006 and 2011. CONCLUSIONS: The initial increase in adolescent treatment admissions for methamphetamine abuse from 2004 to 2006, and subsequent decrease between 2006 and 2011, may suggest a change in methamphetamine abuse patterns among adolescents in Cape Town.

Monitoring the prevalence of methamphetamine-related presentations at psychiatric hospitals in Cape Town, South Africa.

OBJECTIVE: This study aimed to determine a demographic profile of methamphetamine (MA)-related admissions to major psychiatric services in Cape Town, obtain a substance use profile from admitted patients, a profile of common MA-related symptoms encountered during the assessment of the patients presenting with MA-related problems, and a brief profile of the psychiatric diagnoses made. METHOD: Staff in six psychiatric hospitals or wards in Cape Town collected data on methamphetamine related admissions between July and December 2008 using a one-page record review form. The data collection form consisted of the patient's demographic details, presenting symptoms, previous admission details, current MA and other substance use information, and DSM-IV diagnosis. RESULTS: A total of 235 forms were completed. Most patients were male (69%) and the mean age was 25 years. The most common presenting symptoms were aggressive behaviour (74%), followed by delusions (59%) and hallucinations (57%). Males were two times more likely to present with aggression as compared to females, while females were significantly more likely to present with depressed mood or euphoric/elevated mood. The majority of patients had substance-induced psychotic disorder (41%), followed by schizophrenia (31%). Twelve percent (12%) had bipolar mood disorder. CONCLUSION: MA-related psychiatric admissions pose serious challenges to all health services dealing with these patients. Further training and treatment protocol development and distribution is indicated.

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). METHODS: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Methamphetamine use and sexual risk behaviour in Cape Town, South Africa: a review of data from 8 studies conducted between 2004 and 2007.

OBJECTIVE: Community studies and studies of admissions to drug treatment centers indicate a dramatic increase in the prevalence of methamphetamine use in Cape Town since 2003. There has also been a substantial increase over this time period in the prevalence of HIV infection among women attending public antenatal clinics in the Western Cape province. This study aimed to review research conducted in Cape Town on the link between methamphetamine use and sexual risk behaviour. METHOD: A review of published research conducted in Cape Town between 2004 and 2007 was undertaken using PubMed, EBSCOhost and Science Direct. RESULTS: Eight studies were identified, both quantitative and qualitative, and focusing on diverse populations, such as learners in school, out of school youth, adults in the community, men who have sex with men and sex workers. The total sample across the studies was 8153. Across multiple studies methamphetamine was fairly consistently associated with early vaginal sex, condom use during sex, having casual sex and other HIV risk behaviours. For some sub-groups the direction of the relationship was in an unexpected direction. CONCLUSION: The consistency of the findings across studies highlights the increased risk for contracting HIV among methamphetamine users, and reinforces the importance of interventions addressing both methamphetamine use and unsafe sexual behaviour among young people and other sectors of the population. The need for further research is also considered, particularly research that will explain some of the racial differences that were found.