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Journal of the International AIDS... Feb 2023Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a... (Review)
Review
INTRODUCTION
Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV.
METHODS
We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0-19 years.
RESULTS AND DISCUSSION
Overall 3626 abstracts and 371 full papers were screened. Four single-arm, innovator-funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment-experienced and virally suppressed children or adolescents. One trial also included treatment-naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment-naïve participants were virally suppressed (one trial). Among treatment-experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug-related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug-related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z-score (height- and age-adjusted) from baseline to 48 weeks was -0.12 (interquartile range [IQR] -0.46, 0.17) to 0.05 (IQR not reported) for spine, and -0.09 (IQR -0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight-for-age z-scores increased by 0.25 from baseline to 48 weeks.
CONCLUSIONS
Four single-arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF-containing regimens over 24-48 weeks. However, further comparative and longer-term safety data are needed in children and adolescents, including on weight and metabolic changes.
Topics: Infant; Humans; Child; Adolescent; Tenofovir; HIV Infections; Anti-HIV Agents; HIV-1; Adenine; Emtricitabine
PubMed: 36823283
DOI: 10.1002/jia2.26037 -
Molecules (Basel, Switzerland) Sep 2021We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models.... (Review)
Review
We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.
Topics: Animals; Antineoplastic Agents; Brain Diseases; Deoxyadenosines; Humans; Inflammation; Metabolic Diseases; Neoplasms; Signal Transduction
PubMed: 34641429
DOI: 10.3390/molecules26195886 -
Current Oncology (Toronto, Ont.) May 2023Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have expanded these options for subsets with specific molecular alterations, such as microsatellite instability (MSI)-high cancers, but additional treatments and combinations are in urgent need to improve outcomes and improve survival of this incurable disease. The fluoropyrimidine-derivative trifluridine, in combination with tipiracil, has been introduced as a third-line treatment, and more recently, it was studied in combination with bevacizumab. This meta-analysis reports on studies with this combination in clinical practice outside clinical trials.
METHODS
A literature search in the Medline/PubMed and Embase databases was executed for finding series of trifluridine/tipiracil with bevacizumab in metastatic colorectal cancer. Criteria for inclusion in the meta-analysis were English or French language of the report, inclusion of twenty or more patients with metastatic colorectal cancer treated with trifluridine/tipiracil in combination with bevacizumab outside of a trial and containing information regarding response rates, progression-free survival (PFS), and overall survival (OS). Information on the demographics of the patients and on adverse effects of treatment was also collected.
RESULTS
Eight series with a total of 437 patients were eligible for the meta-analysis. The performed meta-analysis discovered a summary response rate (RR) of 2.71% (95% confidence interval (CI): 1.11-4.32%) and a disease control rate (DCR) of 59.63% (95% CI: 52.06-67.21%). Summary PFS was 4.56 months (95% CI: 3.57-5.55 months), and summary OS was 11.17 months (95% CI: 10.15-12.19 months). Common adverse effects identified mirrored the adverse-effect profile of the two components of the combination.
CONCLUSION
The current systematic review and meta-analysis reports the efficacy of trifluridine/tipiracil with bevacizumab in advanced lines of therapy for metastatic colorectal cancer in the setting of clinical practice outside clinical trials. Discovery of predictive biomarkers of response to trifluridine/tipiracil with bevacizumab will promote the tailoring of this treatment to individual patients to maximize clinical benefit.
Topics: Humans; Bevacizumab; Uracil; Colorectal Neoplasms; Trifluridine; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Rectal Neoplasms
PubMed: 37366880
DOI: 10.3390/curroncol30060397 -
Biomedical Papers of the Medical... Mar 2024Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation... (Meta-Analysis)
Meta-Analysis Review
Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.
Topics: Child; Animals; Humans; Aged; 8-Hydroxy-2'-Deoxyguanosine; Creatinine; DNA Damage; Comet Assay; Hypertension
PubMed: 37916467
DOI: 10.5507/bp.2023.044 -
Multiple Sclerosis and Related Disorders Mar 2023The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low- to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies.
METHODS
We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost.
RESULTS
Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59-0.83]; p < 0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38-9.72]; p = 0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model.
DISCUSSION
EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline.
Topics: Adult; Humans; Multiple Sclerosis; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Cladribine
PubMed: 36848839
DOI: 10.1016/j.msard.2023.104581 -
The Cochrane Database of Systematic... Mar 2022Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75%... (Review)
Review
BACKGROUND
Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care.
OBJECTIVES
To assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021.
SELECTION CRITERIA
We included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune-modulating therapy was compared with placebo, an active control, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
We identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years. Study characteristics and risk of bias In most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains. Findings We included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid-containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone-iodine [PVP-I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP-I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP-I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56). Four studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP-I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA-I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP-I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP-I or PVA-I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty. Adverse effects Antiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty.
AUTHORS' CONCLUSIONS
The evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP-I alone resolves signs and symptoms by seven days relative to artificial tears. PVP-I or PVA-I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high-level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short- and long-term outcomes.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Conjunctivitis; Conjunctivitis, Viral; Cyclosporine; Dexamethasone; Female; Fluorometholone; Ganciclovir; Humans; Keratoconjunctivitis; Levofloxacin; Lubricant Eye Drops; Male; Middle Aged; Povidone-Iodine; Tacrolimus; Trifluridine; Young Adult
PubMed: 35238405
DOI: 10.1002/14651858.CD013520.pub2 -
AIDS (London, England) Aug 2022Assess adverse perinatal outcomes in pregnant women living with HIV (WLHIV) receiving HAART or zidovudine (ZDV) monotherapy, compared with antiretroviral therapy... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Assess adverse perinatal outcomes in pregnant women living with HIV (WLHIV) receiving HAART or zidovudine (ZDV) monotherapy, compared with antiretroviral therapy (ART)-naive WLHIV and HIV-negative women.
DESIGN
Systematic review and meta-analysis.
METHODS
We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, and EMBASE for studies published between 1 January 1980 and 20 April 2020. We included studies reporting on the association of pregnant WLHIV receiving HAART or ZDV monotherapy with 11 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB (sPTB), low birth weight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Random-effects meta-analyses were conducted.
RESULTS
Sixty-one cohort studies assessing 409 781 pregnant women were included. WLHIV receiving ZDV monotherapy were associated with a decreased risk of PTB [relative risk 0.70, 95% confidence interval (CI) 0.62-0.79] and LBW (0.77, 0.67-0.88), and comparable risk of SGA, compared with ART-naive WLHIV. WLHIV receiving ZDV monotherapy had a comparable risk of PTB and LBW, and an increased risk of SGA (1.16, 1.04-1.30) compared with HIV-negative women. In contrast, WLHIV receiving HAART were associated with a comparable risk of PTB and LBW, and increased risk of SGA (1.38, 1.09-1.75), compared with ART-naive WLHIV. WLHIV receiving HAART were associated with an increased risk of PTB (1.55, 1.38-1.74), sPTB (2.09, 1.48-2.96), LBW (1.79, 1.51-2.13), term LBW (1.88, 1.23-2.85), SGA (1.80,1.34-2.40), and VSGA (1.22, 1.10-1.34) compared with HIV-negative women.
CONCLUSION
Pregnant WLHIV receiving HAART have an increased risk of a wide range of perinatal outcomes compared with HIV-negative women.
Topics: Antiretroviral Therapy, Highly Active; Female; HIV Infections; Humans; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Zidovudine
PubMed: 35608111
DOI: 10.1097/QAD.0000000000003248 -
Reviews in Medical Virology Jul 2023WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of long-acting cabotegravir versus oral tenofovir disoproxil fumarate-emtricitabine as HIV pre-exposure prophylaxis: A systematic review and meta-analysis.
WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection. However, due to social, psychological and other reasons, the compliance with daily oral TDF-FTC in real life is low. Long-acting cabotegravir is currently the only long-acting drug approved by the U.S. Food and Drug Administration (FDA) for HIV PrEP. Due to the long dosing interval (8 weeks), long-acting cabotegravir has low compliance requirements for people at high risk of HIV infection. We aimed to discuss the feasibility of long-acting cabotegravir to replace TDF-FTC as HIV PrEP based on efficacy and safety analyses. Randomized controlled trials were retrieved, and R software was used for meta-analysis after data extraction. and discussion: Results of the meta-analysis showed that compared with TDF-FTC, long-acting cabotegravir was associated with a lower risk of HIV infection (HR = 0.22, 95% CI: 0.08-0.59, p < 0.01), less decreased creatinine clearance (RR = 0.96, 95% CI: 0.93-0.99, p < 0.01), but more tolerated injection sites adverse events (p < 0.01). No statistically significant differences were found between long-acting cabotegravir and oral placebo in non-injection-related adverse events (creatine phosphokinase, headache, nasopharyngitis, upper respiratory tract infection and gastroenteritis) (p > 0.05). Long-acting cabotegravir has a manageable safety profile and is more effective than TDF-FTC in preventing HIV infection. Interestingly, decreased creatinine clearance occurred less frequently with long-acting cabotegravir than with TDF-FTC. Long-acting cabotegravir is very promising to replace TDF-TFC in the future, which requires more large-sample, high-quality RCTs to verify.
Topics: Humans; Tenofovir; Emtricitabine; HIV Infections; Anti-HIV Agents; Creatinine; Pre-Exposure Prophylaxis
PubMed: 37198721
DOI: 10.1002/rmv.2460 -
HIV Medicine Jul 2023Prevention of HIV transmission is fundamental to ending the HIV epidemic. Pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine (TDF-FTC) is an established... (Review)
Review
BACKGROUND
Prevention of HIV transmission is fundamental to ending the HIV epidemic. Pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine (TDF-FTC) is an established HIV-prevention method; however, most PrEP services in Europe have been targeted at men who have sex with men (MSM). A survey in 2021 by Women Against Viruses in Europe (WAVE) showed considerable variation in PrEP access and guidance for women throughout Europe. WAVE therefore commissioned this systematic review to provide insight into PrEP provision and barriers to uptake for women in Europe.
METHODS
PubMed, Embase, and Scopus were searched for studies (January 2013-May 2021) that reported on actual (e.g., efficacy and safety) or hypothetical (e.g., awareness, barriers, PrEP impact models) use of oral PrEP involving women (including cis, transgender, pregnant, migrant, and breastfeeding women). Search terms included HIV, pre-exposure prophylaxis (specifically TDF-FTC), and women. Studies performed outside of the World Health Organization European region were excluded.
RESULTS
The search identified 4716 unique citations, and 45 peer-reviewed articles (44 studies) were included. The majority of these studies (34/44 [77%]) included recipients or potential recipients of PrEP, representing 4699 women (243 transgender women). However, few studies were women focused (4/34 [12%]) or took place outside of Western Europe (3/34 [9%]). Across the three clinical studies that reported women-specific outcomes (60 transgender women, 13 pregnant, and 19 cis women), no breakthrough infections were recorded during the use of PrEP. Lack of awareness of PrEP, low self-estimation of HIV acquisition risk, concerns about stigma, lack of protection against other sexually transmitted infections, and PrEP interaction with hormones (for transgender women) were identified as barriers to use. The remaining studies examined healthcare professionals' perceptions of PrEP (9/44 [20%]), asked for public opinion (2/44 [5%]), or modelled the potential of PrEP for HIV prevention (1/44 [2%]).
CONCLUSIONS
This review revealed a notable lack of literature on PrEP for cis and transgender women in Europe. This is synonymous with a lack of PrEP provision for women in this region. Barriers to PrEP uptake are complex and rooted in institutional and societal stigma, which must be addressed at policy level. HIV prevention with PrEP is not 'one size fits all' and requires a nuanced gender-responsive approach. Further research into the use of PrEP in cis, pregnant, breastfeeding, and transgender women is essential if we are to stop HIV transmission by 2030.
Topics: Male; Pregnancy; Humans; Female; Homosexuality, Male; HIV Infections; Anti-HIV Agents; Sexual and Gender Minorities; Tenofovir; Emtricitabine; Pre-Exposure Prophylaxis
PubMed: 37088558
DOI: 10.1111/hiv.13458 -
International Journal of Biometeorology Nov 2022Thermal stress has a direct effect on various types of DNA damage, which depends on the stage of the cell cycle when the cell is exposed to different climate conditions.... (Review)
Review
Thermal stress has a direct effect on various types of DNA damage, which depends on the stage of the cell cycle when the cell is exposed to different climate conditions. A literature review was conducted to systematically investigate and assess the overall effect of heat stress and DNA damage following heat exposure. In this study, electronic databases including PubMed, Scopus, and Web of Science were searched to find relevant literature on DNA damage in different ambient temperatures. Outcomes included (1) measurement of DNA damage in heat exposure, (2) three different quantification methods (comet assay, 8-hydroxy-2-deoxyguanosine (8-OHdG), and γ-H2AX), and (3) protocols used for moderate (31) and high temperatures (42). The evidence shows that long exposure and very high temperature can induce an increase in DNA damage through aggregate in natural proteins, ROS generation, cell death, and reproductive damage in hot-humid and hot-dry climate conditions. A substantial increase in DNA damage occurs following acute heat stress exposure, especially in tropical and subtropical climate conditions. The results of this systematic literature review showed a positive association between thermal stress exposure and inhibition of repair of DNA damage.
Topics: Humans; DNA Damage; 8-Hydroxy-2'-Deoxyguanosine; Heat Stress Disorders; Heat-Shock Response; Hot Temperature
PubMed: 36178536
DOI: 10.1007/s00484-022-02351-w