Efficacy and safety of dolutegravir/lamivudine in virologically suppressed female participants: week 48 data from the pooled TANGO and SALSA studies.

OBJECTIVES: Women represent >50% of people with HIV globally but have historically been underrepresented in clinical trials. We evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) vs continuing their current antiretroviral regimen (CAR) by sex assigned at birth (female and male) in virologically suppressed adults with HIV-1 without prior virological failure in a pooled analysis of two randomized controlled trials. METHODS: This analysis included 48-week data from the phase 3 TANGO and SALSA studies. Primary and key secondary endpoints included proportions of participants with HIV-1 RNA ≥50 and <50 copies/mL at week 48, respectively. Safety was also assessed. RESULTS: Of 1234 participants, 250 (DTG/3TC, n = 133; CAR, n = 117) were female at birth. Week 48 proportions of participants with Snapshot HIV-1 RNA ≥50 copies/mL were similar regardless of sex at birth (DTG/3TC vs CAR: female, <1% [1/133] vs 2% [2/117]; male, <1% [1/482] vs <1% [3/502]). Proportions with HIV-1 RNA <50 copies/mL were high across sexes and treatment groups (DTG/3TC vs CAR: female, 91% [121/133] vs 89% [104/117]; male, 94% [455/482] vs 94% [471/502]). Immunological response with DTG/3TC was slightly higher in female participants. Incidences of adverse events leading to withdrawal and serious adverse events were low and comparable between treatment groups and across sexes. Weight gain was higher with DTG/3TC than with CAR among female participants aged ≥50 years (treatment difference 2.08 kg [95% confidence interval 0.40-3.75]). CONCLUSIONS: Results confirm the robustness of DTG/3TC as a switch option in virologically suppressed females with HIV-1, with outcomes similar to those in males.

Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.

If you build it, will they come? Is test site availability a root cause of geographic disparities in COVID-19 testing?

OBJECTIVES: The purpose of this study was to examine the relationship between test site availability and testing rate within the context of social determinants of health. STUDY DESIGN: A retrospective ecological investigation was conducted using statewide COVID-19 testing data between March 2020 and December 2021. METHODS: Ordinary least squares and geographically weighted regression were used to estimate state and ZIP code level associations between testing rate and testing sites per capita, adjusting for neighbourhood-level confounders. RESULTS: The findings indicate that site availability is positively associated with the ZIP code level testing rate and that this association is amplified in communities of greater economic deprivation. In addition, economic deprivation is a key factor for consideration when examining ethnic differences in testing in medically underserved states. CONCLUSION: The study findings could be used to guide the delivery of testing facilities in resource-constrained states.

Shoe microclimate: An objective characterisation and subjective evaluation.

Shoe microclimate (temperature and humidity) has been suggested to contribute to perceptions of foot thermal comfort. However, limited data is available for perceptual responses in relation to shoe microclimate development both over time and within different areas of the shoe. This study evaluates perceptions of foot thermal comfort for two running shoes different in terms of air permeability in relation to temporal and spatial characteristics of shoe microclimate. The temporal characteristics of shoe microclimate development were similar for both shoes assessed. However, higher temperatures and humidity were observed for the less permeable shoe. Changes to shoe microclimate over time and differences between shoes were perceivable by the users. This study provides the most detailed assessment of shoe microclimate in relation to foot thermal comfort to date, providing relevant information for footwear design and evaluation.

The use of zygomatic implants for the retention of nasal prosthesis following rhinectomy: the Morriston experience.

Reconstruction and rehabilitation following rhinectomy remains controversial and presents a complex problem. Although reconstruction with local and microvascular flaps is a valid option, the aesthetic results may not always be satisfactory. The aesthetic results achieved with a nasal prosthesis are excellent; however patient acceptance relies on a secure method of retention. The technique used and results obtained in a large series of patients undergoing rhinectomy and receiving zygomatic implants for the retention of a nasal prosthesis are described here. A total of 56 zygomatic implants (28 patients) were placed, providing excellent retention and durability with the loss of only one implant in 15 years.

Venues for Meeting Sex Partners and Partner HIV Risk Characteristics: HIV Prevention Trials Network (HPTN064) Women's HIV Seroincidence Study (ISIS).

Identifying venues where women meet sexual partners, particular partners who increase women's risk of acquiring HIV, could inform prevention efforts. We categorized venues where women enrolled in HPTN 064 reported meeting their last three sex partners as: (1) Formal, (2) Public, (3) Private, and (4) Virtual spaces. We used multinomial logistic regression to assess the association between these venues and women's individual characteristics and reports of their partners' HIV risk characteristics. The 2099 women reported meeting 3991 partners, 51 % at Public, 30 % Private, 17 % Formal and 3 % at Virtual venues. Women meeting partners at Formal venues reported more education and condom use than women meeting partners at other venues. Fewer partners met through Formal venues had "high" risk characteristics for HIV than through other venues and hence may pose less risk of HIV transmission. HIV prevention interventions can help women choose partners with fewer risk characteristics across all venue types.

Conductive and evaporative precooling lowers mean skin temperature and improves time trial performance in the heat.

Self-paced endurance performance is compromised by moderate-to-high ambient temperatures that are evident in many competitive settings. It has become common place to implement precooling prior to competition in an attempt to alleviate perceived thermal load and performance decline. The present study aimed to investigate precooling incorporating different cooling avenues via either evaporative cooling alone or in combination with conductive cooling on cycling time trial performance. Ten trained male cyclists completed a time trial on three occasions in hot (35 °C) ambient conditions with the cooling garment prepared by (a) immersion in water (COOL, evaporative); (b) immersion in water and frozen (COLD, evaporative and conductive); or (c) no precooling (CONT). COLD improved time trial performance by 5.8% and 2.6% vs CONT and COOL, respectively (both P < 0.05). Power output was 4.5% higher for COLD vs CONT (P < 0.05). Mean skin temperature was lower at the onset of the time trial following COLD compared with COOL and CONT (both P < 0.05) and lasted for the first 20% of the time trial. Thermal sensation was perceived cooler following COOL and COLD. The combination of evaporative and conductive cooling (COLD) had the greatest benefit to performance, which is suggested to be driven by reduced skin temperature following cooling.

Mild evaporative cooling applied to the torso provides thermoregulatory benefits during running in the heat.

We investigated the effects of mild evaporative cooling applied to the torso, before or during running in the heat. Nine male participants performed three trials: control-no cooling (CTR), pre-exercise cooling (PRE-COOL), and during-exercise cooling (COOL). Trials consisted of 10-min neutral exposure and 50-min heat exposure (30 °C; 44% humidity), during which a 30-min running protocol (70% VO2max ) was performed. An evaporative cooling t-shirt was worn before the heat exposure (PRE-COOL) or 15 min after the exercise was started (COOL). PRE-COOL significantly lowered local skin temperature (Tsk ) (up to -5.3 ± 0.3 °C) (P < 0.001), mean Tsk (up to -2 ± 0.1 °C) (P < 0.001), sweat losses (-143 ± 40 g) (P = 0.002), and improved thermal comfort (P = 0.001). COOL suddenly lowered local Tsk (up to -3.8 ± 0.2 °C) (P < 0.001), mean Tsk (up to -1 ± 0.1 °C) (P < 0.001), heart rate (up to -11 ± 2 bpm) (P = 0.03), perceived exertion (P = 0.001), and improved thermal comfort (P = 0.001). We conclude that the mild evaporative cooling provided significant thermoregulatory benefits during exercise in the heat. However, the timing of application was critical in inducing different thermoregulatory responses. These findings provide novel insights on the thermoregulatory role of Tsk during exercise in the heat.

Sexual Behaviors of US Women at Risk of HIV Acquisition: A Longitudinal Analysis of Findings from HPTN 064.

We describe the sexual behaviors of women at elevated risk of HIV acquisition who reside in areas of high HIV prevalence and poverty in the US. Participants in HPTN 064, a prospective HIV incidence study, provided information about individual sexual behaviors and male sexual partners in the past 6 months at baseline, 6- and 12-months. Independent predictors of consistent or increased temporal patterns for three high-risk sexual behaviors were assessed separately: exchange sex, unprotected anal intercourse (UAI) and concurrent partnerships. The baseline prevalence of each behavior was >30 % among the 2,099 participants, 88 % reported partner(s) with >1 HIV risk characteristic and both individual and partner risk characteristics decreased over time. Less than high school education and food insecurity predicted consistent/increased engagement in exchange sex and UAI, and partner's concurrency predicted participant concurrency. Our results demonstrate how interpersonal and social factors may influence sustained high-risk behavior by individuals and suggest that further study of the economic issues related to HIV risk could inform future prevention interventions.

Warm temperature stimulus suppresses the perception of skin wetness during initial contact with a wet surface.

BACKGROUND/PURPOSE: In the absence of humidity receptors in human skin, the perception of skin wetness is considered a somatosensory experience resulting from the integration of temperature (particularly cold) and mechanical inputs. However, limited data are available on the role of the temperature sense. METHODS: Wet and dry stimuli at 4°C and 8°C above local skin temperature were applied on the back of seven participants (age 21 ± 2 years) while skin temperature and conductance, thermal and wetness perceptions were recorded. RESULTS: Resting local skin temperature was always increased by the application of the stimuli (+0.5-+1.4°C). No effect of stimulus wetness was found on wetness perceptions (P > 0.05). The threshold (point '-2 slightly wet' on the wetness scale) to identify a clearly perceived wetness was never reached during any stimulations and participants did not perceive that some of the stimuli were wet. Overall, warm temperature stimuli suppressed the perception of skin wetness. CONCLUSION: We conclude that it is not the contact of the skin with moisture per se, but rather the integration of particular sensory inputs (amongst which coldness seems dominant) which drives the perception of skin wetness during the initial contact with a wet surface.

Thermal and tactile interactions in the perception of local skin wetness at rest and during exercise in thermo-neutral and warm environments.

The central integration of thermal (i.e. cold) and mechanical (i.e. pressure) sensory afferents is suggested as to underpin the perception of skin wetness. However, the role of temperature and mechanical inputs, and their interaction, is still unclear. Also, it is unknown whether this intra-sensory interaction changes according to the activity performed or the environmental conditions. Hence, we investigated the role of peripheral cold afferents, and their interaction with tactile afferents, in the perception of local skin wetness during rest and exercise in thermo-neutral and warm environments. Six cold-dry stimuli, characterized by decreasing temperatures [i.e. -4, -8 and -15 °C below the local skin temperature (T(sk))] and by different mechanical pressures [i.e. low pressure (LP): 7 kPa; high pressure (HP): 10 kPa], were applied on the back of 8 female participants (age 21 ± 1 years), while they were resting or cycling in 22 or 33 °C ambient temperature. Mean and local Tsk, thermal and wetness perceptions were recorded during the tests. Cold-dry stimuli produced drops in Tsk with cooling rates in a range of 0.06-0.4 °C/s. Colder stimuli resulted in increasing coldness and in stimuli being significantly more often perceived as wet, particularly when producing skin cooling rates of 0.18 °C/s and 0.35 °C/s. However, when stimuli were applied with HP, local wetness perceptions were significantly attenuated. Wetter perceptions were recorded during exercise in the warm environment. We conclude that thermal inputs from peripheral cutaneous afferents are critical in characterizing the perception of local skin wetness. However, the role of these inputs might be modulated by an intra-sensory interaction with the tactile afferents. These findings indicate that human sensory integration is remarkably multimodal.

Rilpivirine versus efavirenz in HIV-1-infected subjects receiving emtricitabine/tenofovir DF: pooled 96-week data from ECHO and THRIVE Studies.

OBJECTIVES: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies. METHODS: ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated. RESULTS: At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities. CONCLUSIONS: The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.

Subgroup analysis of virological response rates with once- and twice-daily darunavir/ritonavir in treatment-experienced patients without darunavir resistance-associated mutations in the ODIN trial.

BACKGROUND: ODIN (once-daily darunavir in treatment-experienced patients) was a 48-week, phase III, randomized, open-label trial comparing once-daily (qd) darunavir/ritonavir (DRV/r) 800/100 mg with twice-daily (bid) DRV/r 600/100 mg, both with an optimized background regimen [OBR; at least two nucleoside reverse transcriptase inhibitors (NRTIs)], in treatment-experienced, HIV-1-infected adults with no DRV resistance-associated mutations (RAMs) at screening. Week 48 analyses of virological response by subgroups are reported. METHODS: A total of 590 patients were randomized to receive qd (n=294) or bid (n=296) DRV/r. Virological response (HIV-1 RNA <50 copies/mL) was assessed according to: screening HIV-1 RNA (≥ or <50000 copies/mL), CD4 cell count, prior protease inhibitor (PI) use, number of active NRTIs in the OBR, presence of mutations (primary PI mutations, PI RAMs or M184V/I), gender, age, race, HIV-1 clade and adherence. RESULTS: Baseline characteristics were well balanced between arms and across subgroups. Response rates were comparable between qd and bid DRV/r treatments for all subgroups examined. Response rates were 78.4 and 76.8% in the qd and bid treatment arms, respectively, in patients with baseline HIV-1 RNA ≤ 50000 copies/mL and 52.8% in both arms in those with > 50000 copies/mL. Response rates for the qd and bid treatment arms by baseline CD4 cell count were also similar (69.6 vs. 65.2% for <200 cells/µL; 72.2 vs. 74.8% for 200- <350 cells/µL; 77.0 vs. 74.3% for ≥ 350 cells/µL). CONCLUSIONS: DRV/r administered either qd or bid provided effective treatment for antiretroviral treatment-experienced patients with no DRV RAMs, with comparable response rates across all subgroups studied. Low patient numbers in specific subgroups may limit interpretation of these specific subgroup results.

Effect of gender and race on the week 48 findings in treatment-naïve, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE.

OBJECTIVES: A week 48 efficacy and safety analysis with respect to gender and race was conducted using pooled data from the phase III, double-blind, double-dummy efficacy comparison in treatment-naïve, HIV-infected subjects of TMC278 and efavirenz (ECHO) and TMC278 against HIV, in a once-daily regimen versus efavirenz (THRIVE) trials. METHODS: Treatment-naïve, HIV-1-infected adults were randomized to receive rilpivirine (RPV; TMC278) 25 mg once a day (qd), or efavirenz (EFV) 600 mg qd, plus tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine (THRIVE). RESULTS: A total of 1368 participants (76% male and 61% White, of those with available race data) were randomized and treated. No gender-related differences in response rate (percentage of patients with HIV-1 viral load < 50 HIV-1 RNA copies/mL, using an intent-to-treat, time-to-loss-of-virological-response algorithm) were observed (RPV: men, 85%; women, 83%; EFV: men, 82%; women, 83%). Response rates were lower in Black compared with Asian and White participants (RPV: 75% vs. 95% and 85%, respectively; EFV: 74% vs. 93% and 83%, respectively); this finding was mostly a result of higher discontinuation and virological failure rates in Black patients. Safety findings were generally similar across race and gender subgroups. However, nausea occurred more commonly in women than in men in both treatment groups. In men, diarrhoea was more frequent in the EFV group, and abnormal dreams/nightmares were more frequent in men in both the EFV and RPV groups. CONCLUSIONS: Overall response rates were high for both RPV and EFV. No gender differences were observed. However, response rates were lower among Black patients, regardless of treatment group. Gender appeared to influence the incidence of gastrointestinal adverse events and abnormal dreams/nightmares for both treatments.

A randomised controlled trial comparing fixation of mandibular angle fractures with a single miniplate placed either transbuccally and intra-orally, or intra-orally alone.

This study compared fixation of simple mandibular angle fractures with a single miniplate either placed from a combined transbuccal and intra-oral approach, or intra-orally alone. 140 consecutive patients were randomly allocated to the two treatment groups. Complications were noted and compared. An email questionnaire to all the participating surgeons examined their personal preferences between the two methods. 20% of plates needed to be removed during the 3 month study period in the combined transbuccal/intra-oral group compared with 36% in the intra-oral alone group (p

Impact of perioperative hyperbaric oxygen therapy on the quality of life of maxillofacial patients who undergo surgery in irradiated fields.

From 2001 to 2005, 66 patients referred for perioperative hyperbaric oxygen therapy (HBO2) for debridement of necrotic tissue or prevention of radionecrosis were assessed with quality of life measures, before and after completion of HBO2 and surgery. The Medical Outcomes Short Form 36 (SF-36) and Hospital Anxiety and Depression Scale (HADS) showed no significant changes. The European Organisation for Research and Treatment of Cancer Core (EORTC-C30) questionnaire showed significant improvement in pain, global health, and dyspnoea (p=0.011; p=0.027; p=0.008, respectively). The Head and Neck sub-module (H&N35) identified significant improvements in teeth, dry mouth and social contact (p=0.002; p=0.038; p=0.029, respectively). The University of Washington Scale (UW), showed significant changes in relation to chewing and shoulders (p=0.031; p=0.047). When sub-group analysis using 'osteoradionecrosis' and 'dental extraction or implants' was performed on the EORTC and UW data, variations in the patterns of significance were found. Adjunctive HBO2 should be considered for the treatment and prevention of some of the long-term complications of radiotherapy.

Acute perioperative normovolaemic haemodilution in major maxillofacial surgery.

Extensive blood loss can occur when patients have major operations for head and neck neoplasia. The risks and costs of allogeneic blood transfusion have been well documented. Acute perioperative normovolaemic haemodilution (APNH) is a method of saving blood and autologous transfusion. The purpose of this study was to compare a group of patients having major head and neck operations who had APNH, with a historical group, to assess the need for allogeneic transfusion. Of the 21 patients who had APNH only one patient required allogeneic blood. In the historical group of 24 patients, 15 patients had required allogeneic blood (p=0.0001). APNH is an economic, safe and practical way of saving blood.

Mitochondrial DNA mutations in oral squamous cell carcinoma.

It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations within the ND2 gene of histologically normal parotid salivary gland tissue of smokers may be molecular biomarkers for smoking-induced mtDNA damage. Oral squamous cell carcinoma (SCC) is strongly related to cigarette smoking; therefore, we used PCR and direct sequencing to establish whether mtDNA mutations were also present in oral SCC which could be used as additional biomarkers for smoking-associated DNA damage. In addition to searching for mutations in the ND2 gene, the mitochondrial D-Loop was also analysed. Three mutation hotspots were observed in the D-Loop at nt 146, 152 and 186, two of which (nt 146 and 152) have also been implicated in oesophageal SCC, another smoking-related cancer. The mutation hotspot observed at nt 186 has not previously been reported in other tumours. Furthermore, we show that the mutations previously reported within the ND2 gene in normal parotid tissue of smokers were not evident in these samples, but that a mutation hotspot occurs at nucleotide 4917 in oral SCC. We also show that D-Loop mutations occur predominantly in male smokers and female non-smokers and that this association with gender is statistically significant (P = 0.003). We conclude that the mtDNA mutation hotspots found in this study, in particular nt 186, are potential biomarkers for oral SCC. However, owing to gender-specific differences in occurrence in smokers and non-smokers, and a lack of environmental smoking history, in general, it is difficult to associate these mutations with mtDNA damage induced by smoking. If the mutations observed in the subset of male patients are smoking induced, given our previous findings, mutation hotspots in the ND2 gene may be tissue specific suggesting the causative mutagens for mtDNA damage within these tissues are likely to be different.

Titanium plate reconstruction of the osseous defect after harvest of a composite free flap using the deep circumflex iliac artery.

Hernia formation following harvest of bicortical iliac crest bone occurs infrequently as a late complication and may lead to chronic pain at the donor site and rarely to obstruction and strangulation of bowel. We describe the use of a custom-made titanium plate used to reconstruct the iliac donor site following harvest of a DCIA composite free flap. A pre-operative 3D CT and stereolithography model of the ilium are used to fabricate a titanium plate of the desired shape and size. This plate is used to reconstruct the donor site defect at the time of primary surgery. This technique may reduce late complications following DCIA composite free flap harvest.