Acupuncture for de Quervain's tenosynovitis: A randomized controlled trial.

BACKGROUND: Acupuncture has been an alternative approach for de Quervain's tenosynovitis (DQt), but trial evidence is still lacking. PURPOSE: This study aimed to assess the efficacy of acupuncture in patients with DQt. STUDY DESIGN: A randomized controlled trial. METHODS: A total of 68 subjects with DQt were recruited from outpatients of Department of Orthopaedics and Traumatology, and Chinese medicine clinics, The University of Hong Kong, and were randomized into the acupuncture group (n = 34) and the waitlist group (n = 34). Subjects in the acupuncture group received 5 acupuncture sessions over 2 weeks, followed by a 10-week follow-up. The waitlist control group received assessments only in the first 6 weeks of the waiting period and received the same acupuncture treatment and follow-up as the treatment group in the next 12 weeks. The primary outcome was the general pain intensity using the Visual Analogue Scale (VAS) at the end of treatment (week 2). Secondary outcomes were grip and pinch strengths of affected hands, the quick Disabilities of the Arm, Shoulder and Hand Score (Q-DASH), and the World Health Organization Quality of Life-brief Questionnaire (WHOQOL-BREF) at weeks 2 and 6. RESULTS: From baseline to 2 weeks, the mean VAS score decreased by 19.5 points in the acupuncture group and by 3.4 points in the waitlist group. The difference for acupuncture vs waitlist control was -16.2 points (95% CI, -26.7 to -5.6, p = 0.003). Acupuncture effects sustained for 10 weeks (mean difference compared with baseline, -30.6; 95% CI, -39.6 to -21.7). Secondary outcomes showed that acupuncture reduced pain intensity, improved grip and pinch strength of affected hands, and Q-DASH scores, but not the scores of WHOQOL-BREF in patients. No serious adverse event occurred during the study period. CONCLUSIONS: Our findings support that 2-week of acupuncture is safe and effective in the reduction of pain intensity, and improvement of strengths and disabilities of hand in DQt patients. Acupuncture also has long-term effects on DQt. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov (NCT03472443).

Sexual behaviour during COVID-19: a repeated cross-sectional survey in Victoria, Australia.

BACKGROUND: During 2020, the State of Victoria (Australia) experienced two COVID-19 waves. Both resulted in community lockdowns followed by eased restrictions. We examined variation of sexual behaviour in Victorians over time during COVID-19. METHODS: We conducted a repeated online survey at four timepoints corresponding with two lockdown (LD1, LD2) and two reduced restriction (RR1, RR2) periods in Victoria. A convenience sample of participants aged ≥18years was recruited via social media and asked about their recent (past 4weeks) sexual behaviour. Using multivariable logistic regression, we investigated variation in sexual behaviour between surveys. RESULTS: A total of 1828 surveys were completed; 72% identified as female, 69% were aged 18-29years, 90% were metropolitan residents. The proportion reporting recent partnered sex ranged from 54.9% (LD2) to 70.2% (RR1). Across all timepoints, the most common sexual partners were regular (81.5%, n =842) and 10.8% (n =111) reported casual partners (e.g. hook-ups). Compared with LD1, respondents were >2-fold more likely to report casual partner(s) during reduced restrictions (RR1: aOR 2.0; 95% CI 1.1-3.7; RR2: aOR 2.8; 95% CI 1.3-5.9). Across all timepoints, 26.6% (n =486) reported using dating apps. Compared with LD1, dating app use for face-to-face activities (e.g. dates, hook-ups) was >4-fold higher during reduced restrictions (RR1: aOR 4.3; 95% CI 2.3-8.0; RR2: aOR 4.1; 95% CI 1.9-8.8). App use for distanced activities (e.g. sexting, virtual dates) was highest during LD1 (48.8%) than other periods. CONCLUSIONS: In this convenience sample, self-reported sexual behaviours fluctuated between lockdowns and reduced restrictions. While dating apps may provide a mechanism for virtual connections, this may be temporary until physical connections are possible.

Rectal chlamydia infections: implications for reinfection risk, screening, and treatment guidelines.

PURPOSE OF REVIEW: Rectal chlamydia is a prevalent sexually transmissible infection in both men who have sex with men (MSM) and in women. Screening is recommended for MSM but remains controversial for women. The optimal treatment for rectal chlamydia is now conclusive but interpreting and managing positive results remains challenging. Infections among MSM are increasing and strategies are needed to reduce incident infections. This review summarizes recent developments for the screening and management of rectal chlamydia and its implications on reinfection. RECENT FINDINGS: Reinfections in MSM may be occurring due to resumption of sex soon after treatment whereas repeat infections in women may occur due to autoinoculation in the absence of sex. Doxycycline is now first-line treatment but its role in chemoprophylaxis remains unclear. False positive results remain an issue, but the development of viability assays may prove useful in future to determine true infections. SUMMARY: Doxycycline is the first-line treatment for rectal chlamydia and in women may prevent infections at the urogenital site. Viability assays can help to reduce antibiotic use once developed. The role of routine screening of rectal chlamydia in women remains unclear and this debate may soon include asymptomatic infections in MSM.

Metabolic Plasticity and Combinatorial Radiosensitisation Strategies in Human Papillomavirus-Positive Squamous Cell Carcinoma of the Head and Neck Cell Lines.

BACKGROUND: A major objective in the management of human papillomavirus (HPV)-positive squamous cell carcinoma of the head and neck (SCCHN) is to reduce long-term functional ramifications while maintaining oncological outcomes. This study examined the metabolic profile of HPV-positive SCCHN and the potential role of anti-metabolic therapeutics to achieve radiosensitisation as a potential means to de-escalate radiation therapy. METHODS: Three established HPV-positive SCCHN cell lines were studied (UM-SCC-104, UPCI:SCC154, and VU-SCC-147), together with a typical TP53 mutant HPV-negative SCCHN cell line (UM-SCC-81B) for comparison. Metabolic profiling was performed using extracellular flux analysis during specifically designed mitochondrial and glycolytic stress tests. Sensitivity to ionising radiation (IR) was evaluated using clonogenic assays following no treatment, or treatment with: 25 mM 2-deoxy-D-glucose (glycolytic inhibitor) alone; 20 mM metformin (electron transport chain inhibitor) alone; or 25 mM 2-deoxy-D-glucose and 20 mM metformin combined. Expression levels of p53 and reporters of p53 function (MDM2, p53, Phospho-p53 [Ser15], TIGAR and p21 [CDKN1A]) were examined by western blotting. RESULTS: HPV-positive SCCHN cell lines exhibited a diverse metabolic phenotype, displaying robust mitochondrial and glycolytic reserve capacities. This metabolic profile, in turn, correlated with IR response following administration of anti-metabolic agents, in that both 2-deoxy-D-glucose and metformin were required to significantly potentiate the effects of IR in these cell lines. CONCLUSIONS: In contrast to our recently published data on HPV-negative SCCHN cells, which display relative glycolytic dependence, HPV-positive SCCHN cells can only be sensitised to IR using a complex anti-metabolic approach targeting both mitochondrial respiration and glycolysis, reflecting their metabolically diverse phenotype. Notionally, this may provide an attractive platform for treatment de-intensification in the clinical setting by facilitating IR dose reduction to minimise the impact of treatment on long-term function.

Trust and Trade-Offs in Sharing Data for Precision Medicine: A National Survey of Singapore.

BACKGROUND: Precision medicine (PM) programs typically use broad consent. This approach requires maintenance of the social license and public trust. The ultimate success of PM programs will thus likely be contingent upon understanding public expectations about data sharing and establishing appropriate governance structures. There is a lack of data on public attitudes towards PM in Asia. METHODS: The aim of the research was to measure the priorities and preferences of Singaporeans for sharing health-related data for PM. We used adaptive choice-based conjoint analysis (ACBC) with four attributes: uses, users, data sensitivity and consent. We recruited a representative sample of n = 1000 respondents for an in-person household survey. RESULTS: Of the 1000 respondents, 52% were female and majority were in the age range of 40-59 years (40%), followed by 21-39 years (33%) and 60 years and above (27%). A total of 64% were generally willing to share de-identified health data for IRB-approved research without re-consent for each study. Government agencies and public institutions were the most trusted users of data. The importance of the four attributes on respondents' willingness to share data were: users (39.5%), uses (28.5%), data sensitivity (19.5%), consent (12.6%). Most respondents found it acceptable for government agencies and hospitals to use de-identified data for health research with broad consent. Our sample was consistent with official government data on the target population with 52% being female and majority in the age range of 40-59 years (40%), followed by 21-39 years (33%) and 60 years and above (27%). CONCLUSIONS: While a significant body of prior research focuses on preferences for consent, our conjoint analysis found consent was the least important attribute for sharing data. Our findings suggest the social license for PM data sharing in Singapore currently supports linking health and genomic data, sharing with public institutions for health research and quality improvement; but does not support sharing with private health insurers or for private commercial use.

The prevalence of oropharyngeal squamous cell carcinoma in patients admitted with symptoms of peritonsillar abscess or cellulitis: A retrospective multicentre study.

OBJECTIVES: Anecdotal evidence suggests that oropharyngeal squamous cell carcinoma (OPSCC) should be suspected in patients presenting with symptoms of peritonsillar abscess (PTA) or cellulitis (PTC). The aim of this study was to estimate the prevalence of OPSCC in patients presenting with symptoms of PTA/PTC. METHOD, SETTING AND PARTICIPANTS: We retrospectively identified all adults with a coded diagnosis of PTA or PTC who presented between 2012 and 2016 inclusive, across six ENT units in Merseyside. Records were compared to that of the centralised regional head and neck cancer database. The clinical records of a subset of patients were reviewed for the purposes of data validation. RESULTS: A total of 1975 patients with PTA/PTC were identified. Three patients were subsequently diagnosed with OPSCC. None of the three actually had an objective underlying diagnosis of PTA/PTC on the same side. The prevalence of OPSCC in patients admitted with symptoms of PTA/PTC was 0.15% or approximately 1:650 admissions. The records of 510 patients who presented over a one-year period (2016) were reviewed in even greater detail. There were 298 patients with PTA (59.4%) and 151 with PTC (29.1%) and 61 had an alternative diagnosis (11.9%). High-risk features (age ≥40, tonsillar asymmetry or tonsillar lesion) were present in 106 patients (24%). Urgent follow-up was expedited for 77 patients (73%). CONCLUSION: This study estimates the risk of OPSCC in patients with peritonsillar symptoms. The prevalence is low, even in a region with a relatively heavy disease burden. Clinicians should, however, retain a high level of suspicion in patients with persistent symptoms.

Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).

Engineering Pseudomonas putida for efficient aromatic conversion to bioproduct using high throughput screening in a bioreactor.

Pseudomonas putida KT2440 is an emerging biomanufacturing host amenable for use with renewable carbon streams including aromatics such as para-coumarate. We used a pooled transposon library disrupting nearly all (4,778) non-essential genes to characterize this microbe under common stirred-tank bioreactor parameters with quantitative fitness assays. Assessing differential fitness values by monitoring changes in mutant strain abundance identified 33 gene mutants with improved fitness across multiple stirred-tank bioreactor formats. Twenty-one deletion strains from this subset were reconstructed, including GacA, a regulator, TtgB, an ABC transporter, and PP_0063, a lipid A acyltransferase. Thirteen deletion strains with roles in varying cellular functions were evaluated for conversion of para-coumarate, to a heterologous bioproduct, indigoidine. Several mutants, such as the ΔgacA strain improved fitness in a bioreactor by 35 fold and showed an 8-fold improvement in indigoidine production (4.5 g/L, 0.29 g/g, 23% of maximum theoretical yield) from para-coumarate as the carbon source.

Contraceptive use and pregnancy plans among women of reproductive age during the first Australian COVID-19 lockdown: findings from an online survey.

PURPOSE: Australia introduced 'lockdown' measures to control COVID-19 on 22 March 2020 which continued for a period of two months. We aimed to investigate the impact this had on sexual and reproductive health (SRH). MATERIALS AND METHODS: Australians aged 18+ were eligible to participate in an online survey from 23 April to 11 May 2020. We report on the experiences of 518 female participants aged <50 years. Pregnancy intentions and contraceptive use were analysed using descriptive statistics. Odds ratios and 95% confidence intervals were calculated to investigate difficulty accessing SRH products and services. Qualitative data were analysed using conventional content analysis. RESULTS: Most participants were aged 18-24 years, and indicated they were trying to avoid pregnancy. The oral contraceptive pill was the most common single method used however nearly 20% reported they were not using contraception. Women who were employed had less trouble accessing contraception during lockdown. Participants reported delaying childbearing or deciding to remain childfree due to COVID-19. CONCLUSION: COVID-19 lockdown impacted the SRH of Australian women. Findings highlight the importance of continued access to SRH services and products during global emergencies.

Early versus late oral feeding following total (pharyngo)laryngectomy: Systematic review and meta-analysis.

Timing of oral feeding following total laryngectomy is a contentious issue with highly varied practices. Multiple database search was performed to identify studies comparing outcomes of early (≤5 days) versus late (>5 days) oral feeding. Bias assessment was carried out using Cochrane bias tool. Random-effects meta-analysis was used. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The rate of pharyngocutaneous fistula (PCF) in randomized control trials (RCTs) in early versus late feeding was 15.2% versus 11.7% (RR 1.35, 95%CI [0.68-2.7], p = 0.40). The rate of PCF in the cohort studies was 14.1% versus 20.5% (RR 1.0, 95%CI [0.76-1.3], p = 0.98). The length of hospital stay was significantly shorter in the early feeding group (mean difference (days) -4.68 (-6.2 to -3.1, p < 0.0001). Early oral feeding appears to be safe and is associated with shorter hospital stay. However, the quality of evidence is low and the patient characteristics are not representative of current practices.

A prospective multicentre external validation study of the Liverpool Peritonsillar abscess Score (LPS) with a no-examination COVID-19 modification.

OBJECTIVES: Our primary aim was to validate the Liverpool Peritonsillar abscess Score (LPS) externally in a new patient cohort. Our secondary aim was to modify the LPS in the light of the COVID-19 pandemic to produce a no-examination variant for use in this instance. DESIGN: Prospective multicentre external validation study. SETTING: Six different secondary care institutions across the United Kingdom. PARTICIPANTS: Patients over 16 years old who were referred to ENT with any uncomplicated sore throat such a tonsillitis or peritonsillar abscess (PTA). MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value and negative predictive value for both the original LPS model and the modified model for COVID-19. RESULTS: The LPS model had sensitivity and specificity calculated at 98% and 79%, respectively. The LPS has a high negative predictive value (NPV) of 99%. The positive predictive value (PPV) was slightly lower at 63%. Receiver operating characteristic (ROC) curve, including the area under the curve (AUROC), was 0.888 which indicates very good accuracy. CONCLUSIONS: External validation of the LPS against an independent geographically diverse population yields high NPV. This may support non-specialist colleagues who may have concerns about mis-diagnosing a PTA. The COVID-19 modification of the LPS has a similar NPV, which may be of use where routine oral examination is to be avoided during the COVID-19 pandemic.

Love during lockdown: findings from an online survey examining the impact of COVID-19 on the sexual health of people living in Australia.

INTRODUCTION: Australia recorded its first case of COVID-19 in late January 2020. On 22P March 2020, amid increasing daily case numbers, the Australian Government implemented lockdown restrictions to help 'flatten the curve'. Our study aimed to understand the impact of lockdown restrictions on sexual and reproductive health. Here we focus on sexual practices. METHODS: An online survey was open from the 23PP April 2020 to 11P May 2020. Participants were recruited online via social media and other networks and were asked to report on their sexual practices in 2019 and during lockdown. Logistic regression was used to calculate the difference (diff) (including 95% CIs) in the proportion of sex practices between time periods. RESULTS: Of the 1187 who commenced the survey, 965 (81.3%) completed it. Overall, 70% were female and 66.3% were aged 18-29 years. Most (53.5%) reported less sex during lockdown than in 2019. Compared with 2019, participants were more likely to report sex with a spouse (35.3% vs 41.7%; diff=6.4%; 95% CI 3.6 to 9.2) and less likely to report sex with a girl/boyfriend (45.1% vs 41.8%; diff=-3.3%; 95% CI -7.0 to -0.4) or with casual hook-up (31.4% vs 7.8%; 95% CI -26.9 to -19.8). Solo sex activities increased; 14.6% (123/840) reported using sex toys more often and 26.0% (218/838) reported masturbating more often. Dating app use decreased during lockdown compared with 2019 (42.1% vs 27.3%; diff= -14.8%; 95% CI -17.6 to -11.9). Using dating apps for chatting/texting (89.8% vs 94.5%; diff=4.7%; 95% CI 1.0 to 8.5) and for setting up virtual dates (2.6% vs 17.2%; diff=14.6%; 95% CI 10.1 to 19.2) increased during lockdown. CONCLUSION: Although significant declines in sexual activity during lockdown were reported, people did not completely stop engaging in sexual activities, highlighting the importance of ensuring availability of normal sexual and reproductive health services during global emergencies.

Genome-scale metabolic rewiring improves titers rates and yields of the non-native product indigoidine at scale.

High titer, rate, yield (TRY), and scalability are challenging metrics to achieve due to trade-offs between carbon use for growth and production. To achieve these metrics, we take the minimal cut set (MCS) approach that predicts metabolic reactions for elimination to couple metabolite production strongly with growth. We compute MCS solution-sets for a non-native product indigoidine, a sustainable pigment, in Pseudomonas putida KT2440, an emerging industrial microbe. From the 63 solution-sets, our omics guided process identifies one experimentally feasible solution requiring 14 simultaneous reaction interventions. We implement a total of 14 genes knockdowns using multiplex-CRISPRi. MCS-based solution shifts production from stationary to exponential phase. We achieve 25.6 g/L, 0.22 g/l/h, and ~50% maximum theoretical yield (0.33 g indigoidine/g glucose). These phenotypes are maintained from batch to fed-batch mode, and across scales (100-ml shake flasks, 250-ml ambr®, and 2-L bioreactors).

Promoting Quality Improvement in Primary Care Through a Longitudinal, Project-Based, Interprofessional Curriculum.

Introduction: Health professionals must demonstrate competencies in quality improvement (QI) and interprofessional (IP) practice. Yet few curricula are designed to address these competencies in an integrated, longitudinal way. Our experiential IP QI curriculum addresses this gap. Methods: The IP QI curriculum was part of a San Francisco VA Health Care System training program for second-year internal medicine residents and adult gerontology primary care nurse practitioner students, pharmacy residents, and postdoctoral psychology fellows. Trainees worked in mentored IP teams to select, design, implement, evaluate, and present a project as part of a 9-month curriculum. Teaching methodologies included didactics and project-based skills application. Curriculum evaluation included trainees' QI knowledge and skills self-assessments, trainee satisfaction, mentor appraisals, and project results and impact assessments. Results: From 2011-2012 to 2017-2018, 242 trainees completed the curriculum and 41 QI projects. Trainees reported high satisfaction with the introductory sessions (M = 4.4, SD = 0.7). They also reported improvement in comfort with QI knowledge and skills by the curriculum's completion. QI mentors (n = 23) observed growth in trainees' QI knowledge and skills, felt confident in trainees' ability to orchestrate a QI initiative, and believed their mentored QI projects added value to the organization. Thirty-eight projects resulted in system modifications. Discussion: This IP QI curriculum offers team-based, workplace experiences for trainees to learn and apply QI knowledge and skills. Leading factors for successful implementation included attention to team-building and faculty development. Challenges included reliably collecting evaluation data, accurately measuring ongoing systems changes, and variable trainee engagement.

Practitioner perspectives on building capacity for evidence-based public health in state health departments in the United States: a qualitative case study.

BACKGROUND: Public health agencies are responsible for implementing effective, evidence-based public health programs and policies to reduce the burden of chronic diseases. Evidence-based public health can be facilitated by modifiable administrative evidence-based practices (A-EBPs) (e.g., workforce development, organizational climate), yet little is known about how practitioners view A-EBPs. Thus, the purpose of this qualitative study was to understand state health department practitioners' perceptions about how A-EBPs are implemented and what facilitators and barriers exist to using A-EBPs. METHODS: Chronic disease prevention and health promotion program staff who were members of the National Association of Chronic Disease Directors were recruited to participate in telephone interviews using a snowball sampling technique. Interviews were transcribed verbatim, and transcripts were analyzed using a common codebook and the a priori method in NVivo. RESULTS: Twenty seven interviews were conducted with practitioners in four states (5-8 interviews per state). All practitioners felt that their work unit culture is positive and that leadership encouraged and expected staff to use evidence-based processes. Participants discussed the provision of trainings and technical assistance as key to workforce development and how leaders communicate their expectations. Access to evidence, partnerships, and funding restrictions were the most commonly discussed barriers to the use of A-EBPs and EBDM. CONCLUSIONS: Results of this study highlight practitioners' perspectives on promoting evidence-based public health in their departments. Findings can inform the development and refinement of resources to improve A-EBP use and organizational and leadership capacity of state health departments.

Treatment efficacy for pharyngeal Neisseria gonorrhoeae: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Rising gonorrhoea rates require highly effective treatments to reduce transmission and prevent development of antimicrobial resistance. Currently the most effective treatments for pharyngeal gonorrhoea remain unclear. This review aimed to estimate treatment efficacy for pharyngeal gonorrhoea. METHODS: Online bibliographic databases were searched for the period 1 January 2000 to 17 September 2019 for treatments of gonorrhoea. All randomized controlled trials (RCTs) with data on pharyngeal gonorrhoea among participants aged 15 years or above, published in English, were included. Meta-analyses (random effects) were used to estimate the treatment efficacy, defined as microbiological cure, among currently recommended monotherapies and dual therapies, previously recommended but no longer used regimens and emerging drugs under evaluation. Side effects were also summarized. The study protocol was registered on PROSPERO (CRD42020149278). RESULTS: There were nine studies that included 452 participants studying 19 treatment regimens. The overall treatment efficacy for pharyngeal gonorrhoea was 98.1% (95% CI: 93.8%-100%; I2 = 57.3%; P < 0.01). Efficacy was similar for single (97.1%; 95% CI: 90.8%-100.0%; I2 = 15.6%; P = 0.29) and dual therapies (98.0%; 95% CI: 91.4%-100%; I2 = 79.1%; P < 0.01). Regimens containing azithromycin 2 g or ceftriaxone were similarly efficacious. The summary efficacy estimate for emerging drugs was 88.8% (95% CI: 76.9%-97.5%; I2 = 11.2%; P = 0.34). Small sample sizes in each trial was a major limitation. CONCLUSIONS: Regimens containing ceftriaxone or azithromycin 2 g, alone or as part of dual therapies are the most efficacious for pharyngeal gonorrhoea. Further pharyngeal-specific RCTs with adequate sample sizes are needed.

Factors Associated With Early Resumption of Condomless Anal Sex Among Men Who Have Sex With Men After Rectal Chlamydia Treatment.

BACKGROUND: The resumption of sexual activity shortly after commencing treatment for sexually transmitted infections (STIs) is poorly described despite contributing to onward transmission. With azithromycin remaining an option for rectal Chlamydia trachomatis, resuming sex too early after treatment may contribute to antimicrobial resistance because of exposure of newly acquired STIs to subinhibitory concentrations. METHODS: Clinical and sexual behavioral data were collected from men participating in a trial assessing treatment efficacy for rectal chlamydia. Data were collected at recruitment and weekly for 3 weeks after commencing treatment. Outcome measures were resumption of any sexual activity or condomless receptive anal sex within 1, 2, or 3 weeks after commencing treatment. Generalized linear regression was used to calculate adjusted risk ratios (aRR) to identify associated factors. RESULTS: Almost 1 in 10 men (9.5%; 95% confidence interval [CI], 7.2-12.1) resumed condomless receptive anal sex within 1 week of commencing treatment. This was associated with current preexposure prophylaxis use (aRR, 3.4; 95% CI, 2.5-4.8]) and having 9 or more sexual partners in the last 3 months (aRR, 3.2; 95% CI, 1.6-5.0). Most men (75.0%; 95% CI, 71.3-78.5) resumed any sexual activity within 3 weeks; this was associated with a greater number of sexual partners (4-8 partners; aRR, 1.2; 95% CI, 1.1-1.5; ≥9 partners; aRR, 1.5; 95% CI, 1.3-1.7). CONCLUSIONS: Resuming condomless receptive anal sex early after treatment may facilitate onward transmission and promote antimicrobial resistance for STIs. Although azithromycin remains a treatment option, this analysis highlights the need for new health promotion messages regarding early resumption of sex and continued surveillance for antimicrobial resistance.

TP53 mutations in head and neck cancer cells determine the Warburg phenotypic switch creating metabolic vulnerabilities and therapeutic opportunities for stratified therapies.

Patients with mutated TP53 have been identified as having comparatively poor outcomes compared to those retaining wild-type p53 in many cancers, including squamous cell carcinomas of the head and neck (SCCHN). We have examined the role of p53 in regulation of metabolism in SCCHN cells and find that loss of p53 function determines the Warburg effect in these cells. Moreover, this metabolic adaptation to loss of p53 function creates an Achilles' heel for tumour cells that can be exploited for potential therapeutic benefit. Specifically, cells lacking normal wild-type p53 function, whether through mutation or RNAi-mediated downregulation, display a lack of metabolic flexibility, becoming more dependent on glycolysis and losing the ability to increase energy production from oxidative phosphorylation. Thus, cells that have compromised p53 function can be sensitised to ionizing radiation by pre-treatment with a glycolytic inhibitor. These results demonstrate the deterministic role of p53 in regulating energy metabolism and provide proof of principle evidence for an opportunity for patient stratification based on p53 status that can be exploited therapeutically using current standard of care treatment with ionising radiation.