Repercussions of the COVID-19 pandemic on the HIV care continuum and related factors in economically disadvantaged nations: an integrated analysis using mixed-methods systematic review.

BACKGROUND: The COVID-19 pandemic affected the self-management and care of people living with HIV, requiring adaptations in the way health services are provided. However, it is unclear how these changes impacted HIV care in low-income countries. METHODS: A systematic review including the current evidence related to changes in HIV care continuum during COVID-19 was conducted through a systematic search in the online databases including CINAHL, OVID-Medline, CAB Direct, and OVID-Embase. A two-step screening process was carried out to include eligible papers and reports according to inclusion criteria. RESULTS: From the searches we identified 21 total studies published between 2021 and 2024, the studies revealed mostly negative impacts on all stages of the HIV care continuum in low-income countries. There were impacts related to the blocking measures due to COVID-19, fear of contracting the disease, difficulties in providing resources such as income, food and transports, reductions in the provision of care from prevention to viral suppression. CONCLUSION: Overall, researchers identified several negative impacts of COVID-19 restrictions on HIV care continuum during pandemic; however, some observations indicated indirect positive impacts on some aspects of HIV care. Decline in HIV care practices during pandemic compared to before pandemic were observed including using preventative methods, counseling and testing, receiving HIV healthcare services, HIV medical appointments, antiretroviral adherence, engagement with treatment, and poor viral suppression. However, in some evidence improvement in ART adherence and PrEP use were observed.

Unveiling the gut-eye axis: how microbial metabolites influence ocular health and disease.

The intricate interplay between the gut microbiota and ocular health has surpassed conventional medical beliefs, fundamentally reshaping our understanding of organ interconnectivity. This review investigates into the intricate relationship between gut microbiota-derived metabolites and their consequential impact on ocular health and disease pathogenesis. By examining the role of specific metabolites, such as short-chain fatty acids (SCFAs) like butyrate and bile acids (BAs), herein we elucidate their significant contributions to ocular pathologies, thought-provoking the traditional belief of organ sterility, particularly in the field of ophthalmology. Highlighting the dynamic nature of the gut microbiota and its profound influence on ocular health, this review underlines the necessity of comprehending the complex workings of the gut-eye axis, an emerging field of science ready for further exploration and scrutiny. While acknowledging the therapeutic promise in manipulating the gut microbiome and its metabolites, the available literature advocates for a targeted, precise approach. Instead of broad interventions, it emphasizes the potential of exploiting specific microbiome-related metabolites as a focused strategy. This targeted approach compared to a precision tool rather than a broad-spectrum solution, aims to explore the therapeutic applications of microbiome-related metabolites in the context of various retinal diseases. By proposing a nuanced strategy targeted at specific microbial metabolites, this review suggests that addressing specific deficiencies or imbalances through microbiome-related metabolites might yield expedited and pronounced outcomes in systemic health, extending to the eye. This focused strategy holds the potential in bypassing the irregularity associated with manipulating microbes themselves, paving a more efficient pathway toward desired outcomes in optimizing gut health and its implications for retinal diseases.

Exploring LGBTQ+ cultural competency and DEI in continuing education: A cross-sectional review of U.S. pharmacy legislation.

BACKGROUND: Lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, or other sexual orientations or gender identities (LGBTQ+) cultural competency training is offered in pharmacy curricula to variable extents. State legislation directly dictates pharmacist training through continuing pharmacy education (CPE) requirements. OBJECTIVES: This study aimed to identify the U.S. states and the District of Columbia (D.C.) that require CPE or training on topics related to LGBTQ+ cultural competency or topics related to diversity, equity, and inclusion (DEI) in general. In addition, this study quantified and compared each state's CPE hours required for each renewal period. METHODS: This cross-sectional study retrospectively examined pharmacy legislation on CPE requirements for each of the 50 U.S. states and D.C. Only state legislation that was signed into law and related to pharmacy practice was included. Official websites for each board of pharmacy were identified to locate lawbooks, laws, rules, regulations, and statutes specific to pharmacy practice. Search terms included "lgbt," "lgbtq," "cultural," "cultural competency," "equity," "health equity," "implicit," and "implicit bias." Two study investigators independently collected data from March 2023 to April 2023. Data were re-reviewed for accuracy in January 2024. Discrepancies were resolved through discussion until a consensus was reached. The total number of required CPE hours, years for each pharmacist license renewal, required LGBTQ+ cultural competency CPE hours, and required DEI-focused CPE hours were described using descriptive statistics. RESULTS: A total of 44 of 51 states and D.C. required 30 CPE hours for each 2-year renewal cycle or 15 CPE hours for each 1-year renewal cycle. California and D.C. had LGBTQ+ cultural competency CPE requirements of 1 CPE hour or 2 CPE hours per cycle, respectively. Five additional states, Illinois, Maryland, Michigan, Oregon, and Washington, required training or CPE on topics related to DEI as a whole. CONCLUSION: Few U.S. states require CPE on LGBTQ+ cultural competency. This study highlights the need for standardized pharmacist training in LGBTQ+ health care.

Age-associated H3K9me2 loss alters the regenerative equilibrium between murine lung alveolar and bronchiolar progenitors.

The lung contains multiple progenitor cell types, but how their responses are choreographed during injury repair and whether this changes with age is poorly understood. We report that histone H3 lysine 9 di-methylation (H3K9me2), mediated by the methyltransferase G9a, regulates the dynamics of distal lung epithelial progenitor cells and that this regulation deteriorates with age. In aged mouse lungs, H3K9me2 loss coincided with fewer alveolar type 2 (AT2) cell progenitors and reduced alveolar regeneration but increased the frequency and activity of multipotent bronchioalveolar stem cells (BASCs) and bronchiolar progenitor club cells. H3K9me2 depletion in young mice decreased AT2 progenitor activity and impaired alveolar injury repair. Conversely, H3K9me2 depletion increased chromatin accessibility of bronchiolar cell genes, increased BASC frequency, and accelerated bronchiolar cell injury repair. These findings indicate that during aging, the epigenetic regulation that coordinates lung progenitor cells' regenerative responses becomes dysregulated, aiding our understanding of age-related susceptibility to lung disease.

Decreased Length of Stay and Opioid Usage After Liver Cancer Surgery With Enhanced Recovery Pathway Implementation.

BACKGROUND AND OBJECTIVES: Enhanced recovery after surgery (ERAS) pathways are associated with better postoperative recovery; however, evidence is lacking in liver cancer surgery. This study aimed to evaluate the impact of an ERAS pathway in US veterans undergoing liver cancer surgery. METHODS: We initiated an ERAS pathway for liver cancer surgery with preoperative, intraoperative, and postoperative interventions, which included a novel regional anesthesia technique, erector spinae plane block, for multimodal analgesia management. A retrospective quality improvement study was conducted with patients undergoing elective open hepatectomy or microwave ablation of liver tumors before and after ERAS pathway implementation. RESULTS: With 24 patients in the post-ERAS group and 23 patients in the pre-ERAS group, we found a significant decreased length of stay in the ERAS group (4.1 days ± 3.9) compared with traditional care (8.6 days ± 7.1, P = .01) and decreased perioperative opioid consumption including intraoperative opioids (post-ERAS 49.8 mg ± 28.5 vs pre-ERAS 98 mg ± 42.3, P = 4.1E-5), postoperative opioids (post-ERAS 65.3 mg ± 59.9 vs pre-ERAS 175.7 mg ± 210.6, P = .018), and patient-controlled analgesia requirements (post-ERAS 0% vs pre-ERAS 50%, P < .001). CONCLUSION: The implementation of ERAS for liver cancer surgery in our veteran population translates into decreased length of stay and perioperative opioid consumption. Although this study is limited as a quality improvement project implemented at one institution with a small sample size, our results are clinically and statistically significant and sufficient to warrant further investigation into the efficacy of ERAS as the surgical needs of the US veteran population increase.

Impact of the COVID-19 pandemic on the HIV care continuum: a mixed methods systematic review protocol.

OBJECTIVE: The objective of this systematic review is to synthesize evidence on the impact of the COVID-19 pandemic on the HIV care continuum for persons living with or at risk of living with HIV. INTRODUCTION: The COVID-19 pandemic affected the self-management and care of people living with HIV. Self-regulation to acquire recurring treatment for HIV is essential for managing symptoms as well as viral suppression. Therefore, this review will systematically appraise and synthesize primary literature on the impact of the COVID-19 pandemic on all phases of the HCC for people living with, or at risk of acquiring, HIV. INCLUSION CRITERIA: This systematic review will include quantitative, qualitative, and mixed methods studies. The search will be limited to studies reporting findings from March 2020. Selected studies must focus on one or more steps of the HIV care continuum, which are diagnosis of HIV infection, linkage to care, retention in care, adherence to antiretroviral therapy, and viral suppression. There are no age, gender, or geographic location restrictions for this review. Studies that examined the impact on other diseases as well as HIV will be included only if the data for HIV can be extracted separately. METHODS: The JBI methodology for convergent integrated mixed methods systematic reviews will guide this review. The following databases will be searched: MEDLINE (Ovid), CINAHL (EBSCOhost), CAB Direct, and Embase. Articles will be screened by 2 independent reviewers. In the case of a disagreement between reviewers, a third independent reviewer will resolve the conflict. Articles will be appraised for methodological quality and their data extracted using an original extraction tool created for the study's purpose. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021285677.

Acute Vulvar Aphthous Ulceration After COVID-19 Vaccination: 3 Cases.

OBJECTIVE: We present a case series of acute vulvar aphthosis immediately following COVID-19 vaccination. MATERIALS AND METHODS: We describe 3 cases of acute vulvar aphthosis following Pfizer Comirnaty BNT162b2 mRNA and AstraZeneca (Vaxzevria) ChAdOx1 nCoV-19 COVID-19 vaccination in adolescent girls. RESULTS: All patients developed vulvar aphthosis within a few days after receiving COVID-19 vaccination. The onset of vulvar aphthosis was observed to correlate with the dosing schedule known to produce the highest likelihood of adverse effects, first dose in AstraZeneca (Vaxzevria) ChAdOx1 nCoV-19 and second dose in Pfizer Comirnaty BNT162b2 mRNA COVID-19 vaccine. Two patients required oral prednisolone and hospital admission for indwelling urinary catheterization due to urinary retention. Full disease resolution with no sequalae was achieved in all three patients. CONCLUSIONS: Clinicians should be aware of the possible risk of vulvar aphthosis after COVID-19 vaccine administration. Nevertheless, its occurrence should not prevent affected patients from receiving future doses of COVID-19 vaccines, as the mortality and morbidity of COVID-19 infection significantly outweigh the risk of vulvar aphthosis recurrence.

Lichen sclerosus in pregnancy: A review of 33 cases.

Vulval lichen sclerosus (VLS) is a chronic inflammatory skin condition affecting the anogenital area in women. Serious long-term consequences of VLS include the risk of developing squamous cell carcinoma of the vulva as well as of scarring and alteration of vulval architecture. The treatment of choice for genital lichen sclerosus in females is potent to very potent topical corticosteroids. There are few published data on the course of VLS in pregnancy. We present our experience of managing 33 pregnancies in 29 women with VLS.

Chronic vulvovaginal candidiasis in patients using a levonorgestrel-containing intrauterine device.

Chronic vulvovaginal candidiasis is usually responsive to therapy with oral antifungals. We present a case series of 13 patients with this condition who were also using a levonorgestrel intrauterine system (LNG-IUS). All cases responded to ongoing oral fluconazole therapy while the LNG-IUS was in situ. The LNG-IUS was removed in six patients and of these, two experienced clinical improvement with lower fluconazole dosage requirements and three experienced complete resolution of symptoms. One remains on fluconazole 100 mg daily.

Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis.

Oestrogen hypersensitivity vulvovaginitis is a rare chronic cyclical vulvovaginitis responsive to oestrogen suppression or antagonism. We present a case series of 16 patients with refractory cyclical vulvovaginitis, all of whom responded to oestrogen suppression with cyproterone acetate.

Management of chronic vulvovaginal candidiasis: a long term retrospective study.

BACKGROUND: Chronic vulvovaginal candidiasis (CVVC) is an unremitting condition causally associated with species of Candida. Limited data are available on its management and long-term outcomes. This retrospective study aimed to explore the long-term outcomes of patients who had experienced symptom remission after a course of oral antifungals. METHODS: Retrospective study conducted over 1 year from data obtained from a vulval dermatology outpatient clinic in Sydney, Australia. Data from 208 patients satisfying presumptive or definitive criteria for CVVC who had been successfully treated with oral azole antifungal medication were collected from a database, including drugs, induction and maintenance treatment regimes, results and adverse effects. RESULTS: Altogether 208 patients commenced an induction regime of oral fluconazole 50-100 mg daily for up to 12 weeks. All patients demonstrated a clinical improvement within 12 weeks. Of the 208 patients, subsequently 95% remained on oral fluconazole for maintenance treatment, 3% changed to other antifungals due to adverse effects and 2% ceased treatment. The most common maintenance regime was oral fluconazole 50 mg twice weekly (46%). Of the study cohort 99% remained on treatment with antifungal therapy for symptom suppression with the mean duration of follow up 26.2 months (range, 5 months to 8.5 years). CONCLUSIONS: Long-term symptom remission was possible in this subset of women with CVVC using fluconazole 50-100 mg or itraconazole 50-100 mg. However, most were unable to cease treatment without experiencing relapse. Adverse effects in this cohort were minimal and there were no cases of drug-induced hepatitis.

Quality of life in patients with chronic vulvovaginal candidiasis: A before and after study on the impact of oral fluconazole therapy.

BACKGROUND/OBJECTIVE: Chronic vulvovaginal candidiasis (CVVC) is a disorder characterised by the signs and symptoms of vulvovaginal inflammation and causally associated with the presence of Candida spp. in the vagina. This study aimed to establish the impact of treatment with fluconazole in CVVC on patients' quality of life (QoL). METHODS: This was a before and after study conducted in vulval dermatology clinics in Sydney, Australia. Patients were assessed at baseline by the dermatology life quality index (DLQI) and visual analogue scale (VAS) grading of erythema at baseline and at 12 weeks after an oral fluconazole regime. The primary outcome measures were a change in their DLQI score and VAS grading. The secondary outcome measures were its tolerability and adverse events. RESULTS: A total of 82 of 91 patients (90%) completed the study. The mean drop in their DLQI score was 11.6 [95% CI (10.1, 13.0)] (P < 0.001). The post-treatment VAS scores were significantly lower than the pretreatment scores (P < 0.001). Adverse effects requiring cessation of fluconazole occurred in 4% of patients. CONCLUSIONS: Fluconazole treatment at a dose of 50-100 mg daily achieved a significant observable and improvement in the QoL of 96% of patients with CVVC within 12 weeks of treatment. Adverse effects were minimal.

Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair.

Ctp1 (also known as CtIP or Sae2) collaborates with Mre11-Rad50-Nbs1 to initiate repair of DNA double-strand breaks (DSBs), but its functions remain enigmatic. We report that tetrameric Schizosaccharomyces pombe Ctp1 contains multivalent DNA-binding and DNA-bridging activities. Through structural and biophysical analyses of the Ctp1 tetramer, we define the salient features of Ctp1 architecture: an N-terminal interlocking tetrameric helical dimer-of-dimers (THDD) domain and a central intrinsically disordered region (IDR) linked to C-terminal 'RHR' DNA-interaction motifs. The THDD, IDR and RHR are required for Ctp1 DNA-bridging activity in vitro, and both the THDD and RHR are required for efficient DSB repair in S. pombe. Our results establish non-nucleolytic roles of Ctp1 in binding and coordination of DSB-repair intermediates and suggest that ablation of human CtIP DNA binding by truncating mutations underlie the CtIP-linked Seckel and Jawad syndromes.

Filtration improves the performance of a high-throughput screen for anti-mycobacterial compounds.

The tendency for mycobacteria to aggregate poses a challenge for their use in microplate based assays. Good dispersions have been difficult to achieve in high-throughput screening (HTS) assays used in the search for novel antibacterial drugs to treat tuberculosis and other related diseases. Here we describe a method using filtration to overcome the problem of variability resulting from aggregation of mycobacteria. This method consistently yielded higher reproducibility and lower variability than conventional methods, such as settling under gravity and vortexing.

The role of platelet factor 4 in radiation-induced thrombocytopenia.

PURPOSE: Factors affecting the severity of radiation-induced thrombocytopenia (RIT) are not well described. We address whether platelet factor 4 (PF4; a negative paracrine for megakaryopoiesis) affects platelet recovery postradiation. METHODS AND MATERIALS: Using conditioned media from irradiated bone marrow (BM) cells from transgenic mice overexpressing human (h) PF4 (hPF4+), megakaryocyte colony formation was assessed in the presence of this conditioned media and PF4 blocking agents. In a model of radiation-induced thrombocytopenia, irradiated mice with varying PF4 expression levels were treated with anti-hPF4 and/or thrombopoietin (TPO), and platelet count recovery and survival were examined. RESULTS: Conditioned media from irradiated BM from hPF4+ mice inhibited megakaryocyte colony formation, suggesting that PF4 is a negative paracrine released in RIT. Blocking with an anti-hPF4 antibody restored colony formation of BM grown in the presence of hPF4+ irradiated media, as did antibodies that block the megakaryocyte receptor for PF4, low-density lipoprotein receptor-related protein 1 (LRP1). Irradiated PF4 knockout mice had higher nadir platelet counts than irradiated hPF4+/knockout litter mates (651 vs. 328 × 106/mcL, p = 0.02) and recovered earlier (15 days vs. 22 days, respectively, p <0.02). When irradiated hPF4+ mice were treated with anti-hPF4 antibody and/or TPO, they showed less severe thrombocytopenia than untreated mice, with improved survival and time to platelet recovery, but no additive effect was seen. CONCLUSIONS: Our studies show that in RIT, damaged megakaryocytes release PF4 locally, inhibiting platelet recovery. Blocking PF4 enhances recovery while released PF4 from megakaryocytes limits TPO efficacy, potentially because of increased release of PF4 stimulated by TPO. The clinical value of blocking this negative paracrine pathway post-RIT remains to be determined.

Platelet factor 4 regulates megakaryopoiesis through low-density lipoprotein receptor-related protein 1 (LRP1) on megakaryocytes.

Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis, but its mechanism of action had not been addressed. Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) has been shown to mediate endothelial cell responses to PF4 and so we tested this receptor's importance in PF4's role in megakaryopoiesis. We found that LRP1 is absent from megakaryocyte-erythrocyte progenitor cells, is maximally present on large, polyploidy megakaryocytes, and near absent on platelets. Blocking LRP1 with either receptor-associated protein (RAP), an antagonist of LDL family member receptors, or specific anti-LRP1 antibodies reversed the inhibition of megakaryocyte colony growth by PF4. In addition, using shRNA to reduce LRP1 expression was able to restore megakaryocyte colony formation in bone marrow isolated from human PF4-overexpressing mice (hPF4(High)). Further, shRNA knockdown of LRP1 expression was able to limit the effects of PF4 on megakaryopoiesis. Finally, infusion of RAP into hPF4(High) mice was able to increase baseline platelet counts without affecting other lineages, suggesting that this mechanism is important in vivo. These studies extend our understanding of PF4's negative paracrine effect in megakaryopoiesis and its potential clinical implications as well as provide insights into the biology of LRP1, which is transiently expressed during megakaryopoiesis.