Perspectives on Injectable HIV Pre-Exposure Prophylaxis: A Qualitative Study of Health Care Providers in the United States.

The introduction of injectable HIV pre-exposure prophylaxis (PrEP) has the potential to significantly change the biomedical HIV prevention landscape. However, effective implementation will require health care providers to adopt, prescribe, and administer injectable PrEP within clinical settings. This study qualitatively examined challenges and benefit of injectable PrEP implementation from the perspective of health care providers. From April to August 2022, we conducted 19 in-depth interviews with current PrEP-prescribing health care providers in New York State, including 3 physician assistants, 5 physicians, and 11 nurse practitioners. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed to report semantic-level themes regarding injectable PrEP implementation. More than half of participants (61%) were aware of injectable PrEP; only 21% had experience prescribing it. Qualitative findings highlighted five themes. Three themes represented implementation challenges, including speculative concerns about side effects, appointment compliance, and practical and logistical considerations. The remaining two themes described benefits of injectable PrEP relative to oral PrEP, which included greater convenience and enhanced privacy. Findings from this qualitative study make significant applied contributions to the sparse knowledge on health care provider perspectives of injectable PrEP post-US Food and Drug Administration approval and their concerns and considerations regarding implementation in real-world clinical settings.

Doxycycline as Postsexual Exposure Prophylaxis: Use, Acceptability, and Associated Sexual Health Behaviors Among a Multi-Site Sample of Clinical Trial Participants.

Doxycycline postexposure prophylaxis (doxy-PEP) reduces sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW). In a clinical trial of doxy-PEP, we sought to assess acceptability, impact, and meaning of doxy-PEP use among MSM/TGW. We conducted semistructured, in-depth 1:1 interviews with MSM and TGW enrolled in the intervention arm of the Doxy-PEP study. We queried motivations for and meaning of use, attitudes, beliefs, adherence, effect on sexual behaviors, and partner, community, and structural factors related to use. We coded interview transcripts into content areas, followed by thematic analysis. We interviewed 44 participants (median age 38), 2% were TGW, 17% Black, 61% White, 30% Hispanic, and 45% persons with HIV. We identified three overarching themes. First, participants found doxy-PEP acceptable, and believed it was effective based on their history of STIs, easy to adhere to, and acceptable to sex partners. Second, doxy-PEP benefited their quality of life and mental health, offering "peace of mind" by reducing their anxiety about acquisition or unwitting transmission of STIs. Participants reported feeling more "in control" of preventing STIs, and positive about supporting their personal, partner, and community health. Third, impact on sexual behavior was variable, with most reporting no change or a brief initial change. Participants in a multi-site clinical trial of doxycycline for STI prevention perceived it to be efficacious, and that it provided quality-of-life benefits, including reduced anxiety and sense of control over sexual health. Doxy-PEP had limited impact on sexual behavior. Clinicaltrials.gov: NCT03980223.

Rapid Initiation of Antiretroviral Therapy Under the Treat-All Policy Reduces Loss to Follow-Up and Virological Failure in Routine Human Immunodeficiency Virus Care Settings in China: A Retrospective Cohort Study (2016-2022).

Following the World Health Organization's guidelines for rapid antiretroviral therapy (ART) initiation [≤7 days after human immunodeficiency virus (HIV) diagnosis], China implemented Treat-All in 2016 and has made significant efforts to provide timely ART since 2017. This study included newly diagnosed HIV adults from Tianjin, China, between 2016 and 2022. Our primary outcome was loss to follow-up (LTFU) at 12 months after enrollment. The secondary outcome was 12-month virological failure. The association between rapid ART and LTFU, as well as virological failure, was assessed via Cox regression and logistic regression. A total of 896 (19.1%) of 4688 participants received ART ≤7 days postdiagnosis. The rate of rapid ART has increased from 7.5% in 2016 to 33.3% by 2022. The rapid ART group had an LTFU rate of 3.3%, as opposed to 5.0% in the delayed group. The rapid ART group had a much reduced virological failure rate (0.6% vs. 1.8%). Rapid ART individuals had a reduced likelihood of LTFU [adjusted hazard ratio: 0.65, 95% confidence intervals (CI): 0.44-0.96] and virological failure (adjusted odds ratio: 0.35, 95% CI: 0.12-0.80). The real-world data indicated that rapid ART is practicable and beneficial for Chinese people with HIV, providing evidence for its widespread implementation and scaling up.

Understanding Attitudes of Postpartum Cisgender Women Toward Integration of HIV Prevention Services into Routine Prenatal and Postpartum Sexual Health Discussions.

Oral pre-exposure prophylaxis (PrEP) is an effective, user-controlled method for HIV prevention. However, awareness, uptake, and adherence to PrEP remain low among cisgender women (CGW). The prenatal and postpartum periods present an opportunity for delivery of comprehensive sexual health services that include HIV prevention education and services. However, little is known about postpartum CGW's attitudes toward integration of HIV prevention education and services into obstetric care in the US. We conducted semistructured interviews with 20 postpartum CGW in the Bronx, NY from July to November 2022 to explore their experiences with prenatal and postpartum sexual health care, examine their attitudes toward integration of HIV prevention services into obstetric sexual health care, and identify components of future implementation strategies. Transcripts were analyzed thematically using a framework approach. Among CGW interviewed, fewer than half reported prior knowledge of PrEP. Ten participants preferred long-acting injectable PrEP relative to six who preferred daily oral PrEP. Most participants reported no discussion of sex with their provider during pregnancy, and when discussions occurred, they focused on permission or prohibition of sexual activity. Participants described a reliance on providers to lead prenatal sexual health discussions. Even when not perceived as personally relevant, most respondents valued education on HIV prevention and PrEP services. In the postpartum period, sexual health discussions were similarly limited despite participants describing complex experiential sexual health concerns. This study supports the potential for integration of HIV prevention education and services into routine prenatal and postpartum sexual health discussions in an area of high HIV prevalence in the US.

Prebiotic utilisation provides Lactiplantibacillus plantarum a competitive advantage in vitro, but is not reflected by an increased intestinal fitness.

Synbiotics combine the concepts of probiotics and prebiotics to synergistically enhance the health-associated effects of both components. Previously, we have shown that the intestinal persistence of inulin-utilizing L. plantarum Lp900 is significantly increased in rats fed an inulin-supplemented, high-calcium diet. Here we employed a competitive population dynamics approach to demonstrate that inulin and GOS can selectively enrich L. plantarum strains that utilize these substrates for growth during in vitro cultivation, but that such enrichment did not occur during intestinal transit in rats fed a GOS or inulin-supplemented diet. The intestinal persistence of all L. plantarum strains increased irrespective of their prebiotic utilization phenotype, which was dependent on the calcium level of the diet. Analysis of fecal microbiota and intestinal persistence decline rates indicated that prebiotic utilization capacity did not selectively stimulate intestinal persistence in prebiotic supplemented diets. Moreover, microbiota and organic acid profile analyses indicate that the prebiotic utilizing probiotic strains are vastly outcompeted by the endogenous prebiotic-utilizing microbiota, and that the collective enhanced persistence of all L. plantarum strains is most likely explained by their well-established tolerance to organic acids.

Oral administration of PEDV-dissolved Alg-CS gel induces high and sustained mucosal immunity in mice.

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.

755-nm picosecond laser plus topical 20% azelaic acid compared to topical 20% azelaic acid alone for the treatment of melasma: a randomized, split-face and controlled trial.

PURPOSE: Melasma remains a refractory skin condition that needs to be actively explored. Azelaic acid has been used for decades as a topical agent to improve melasma through multiple mechanisms, however, there is a lack of research on its combination with laser therapy. This study evaluated the effectiveness of isolated treatment with topical 20% azelaic acid and its combination with 755-nm picosecond laser in facial melasma patients. METHODS: A randomized, evaluator-blinded, controlled study was conducted on 30 subjects with facial melasma in a single center from October 2021 to April 2022. All subjects received topical 20% azelaic acid cream (AA) for 24 weeks, and after 4 weeks, a hemiface was randomly assigned to receive 755-nm picosecond (PS) laser therapy once every 4 weeks for 3 treatments. Treatment efficacy was determined by mMASI score evaluations, dermoscopic assessment, reflectance confocal microscopy (RCM) assessments and patient's satisfaction assessments (PSA). RESULTS: Treatment with 20% azelaic acid, with or without picosecond laser therapy, significantly reduced the hemi-mMASI score (P < 0.0001) and resulted in higher patient satisfaction. Improvements in dermoscopic and RCM assessments were observed in both sides of the face over time, with no difference between the two sides. RCM exhibited better dentritic cell improvement in the combined treatment side. No patients had serious adverse effects at the end of treatment or during the follow-up period. CONCLUSION: The additional use of picosecond laser therapy showed no clinical difference except for subtle differences detected by RCM assessments.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051294; 18 September 2021).

Adverse events related to drug-drug interactions in COVID-19 patients. A persistent concern in the post-pandemic era: a systematic review.

INTRODUCTION: Since COVID-19 patients are often polytreated, monitoring drug-drug interaction (DDIs) is necessary. We evaluated whether drugs used after the second COVID-19 pandemic wave were associated with DDI-related adverse events and the role of drug interaction checkers in identifying them. METHODS: The study (PROSPERO-ID: CRD42024507634) included: 1) consulting the drug interaction checkers Drugs.com, Liverpool COVID-19 Interactions, LexiComp, Medscape, and Micromedex; 2) systematic review; 3) reviewed studies analysis; 4) evaluating drug interaction checkers potential to anticipate DDI-related adverse events.The systematic review was performed searching PubMed, Scopus, ScienceDirect, and Cochrane databases from 1 March 2022 to 11 November 2023. Observational studies, and clinical trials were included. Article without reporting direct association between DDIs and adverse events were excluded. The risk of bias was assessed by Newcastle-Ottawa scale. RESULTS: The most frequent DDIs involved nirmatrelvir/ritonavir (N/R) and fluvoxamine. Fifteen studies, including 150 patients and 35 DDI-related outcomes, were analyzed. The most frequent DDIs involved tacrolimus with N/R, resulting in creatinine increase.Eighty percent of reported DDI-related adverse events would have been identified by all drug-interaction checkers, while the remaining 20% by at least 2 of them. CONCLUSIONS: Drug interaction checkers are useful but show inconsistencies. Multiple sources are needed to tailor treatment in the context of COVID-19.

A Quality Improvement Project to Increase Compliance With a Facility Protocol on Surgical Antimicrobial Prophylaxis.

Surgical site infections (SSIs) contribute to negative outcomes for patients and health care organizations. Compliance with clinical practice guidelines likely can help prevent SSIs. An interdisciplinary team at a regional referral center in Michigan sought to reduce SSIs by improving compliance with the facility's preoperative antibiotic selection, dosing, timing, and redosing protocol. The interventions for the quality improvement project included adding the preprocedural antibiotics and doses to the master OR schedule; holding an education session for all preoperative nurses, intraoperative nurses, and anesthesia professionals; and posting a reference guide in the preoperative and intraoperative areas. Compliance with the facility's protocol for antibiotic selection, dosing, and timing significantly improved. However, SSI rates and compliance with redosing recommendations did not change significantly. The team decided to add the antibiotic order information to the master OR schedule permanently. The team plans to consider providing education sessions on administering preprocedural antibiotics outside the OR.

Frequency of diabetic remission, predictors of remission and survival in cats using a low-cost, moderate-intensity, home-monitoring protocol and twice-daily glargine.

OBJECTIVES: The aim of the present study was to retrospectively assess remission rates and survival in diabetic cats managed using a moderate-intensity, low-cost protocol of home blood glucose measurements and insulin adjustment by clients of a cat-only practice, and to determine if predictors of remission, relapse or survival could be identified. METHODS: The records of a cat-only practice were used to identify 174 cats with newly diagnosed diabetes managed using only pre-insulin home blood glucose measurements for insulin dose adjustments based on a protocol provided to clients aimed at maintaining pre-insulin blood glucose in the range of 6.5-11.9 mmol/l (117-214 mg/dl). Cats were excluded for the following reasons: insufficient follow-up in the records; a lack of owner compliance was recorded; they were receiving ongoing corticosteroids for the management of other conditions; they were euthanased at the time of diagnosis; or they were diagnosed with acromegaly or hyperadrenocorticism. RESULTS: Using only pre-insulin blood glucose measurements at home to adjust the insulin dose to maintain glucose in the range of 6.5-11.9 mmol/l, 47% of cats achieved remission, but 40% of those cats relapsed. A minority (16%) of cats were hospitalised for hypoglycaemia. The survival time was significantly longer in cats in remission and Burmese cats. CONCLUSIONS AND RELEVANCE: The cost and time burden of treating diabetic cats may cause some clients to choose euthanasia over treatment. While the highest rates of diabetic remission have been reported in studies of newly diagnosed cats treated with intensive long-acting insulin protocols and low carbohydrate diets, these protocols may not be suitable for all clients. Nearly 50% of cats with newly diagnosed diabetes achieved remission with this low-cost, moderate-intensity, insulin dosing protocol. As remission was significantly associated with survival time, discussing factors in treatment to optimise remission is important, but it is also important to offer clients a spectrum of options. No cats that started treatment in this study were euthanased because the owner did not wish to continue the diabetes treatment.

Sex similarities and dopaminergic differences in interval timing.

Rodent behavioral studies have largely focused on male animals, which has limited the generalizability and conclusions of neuroscience research. Working with humans and rodents, we studied sex effects during interval timing that requires participants to estimate an interval of several seconds by making motor responses. Interval timing requires attention to the passage of time and working memory for temporal rules. We found no differences between human females and males in interval timing response times (timing accuracy) or the coefficient of variance of response times (timing precision). Consistent with prior work, we also found no differences between female and male rodents in timing accuracy or precision. In female rodents, there was no difference in interval timing between estrus and diestrus cycle stages. Because dopamine powerfully affects interval timing, we also examined sex differences with drugs targeting dopaminergic receptors. In both female and male rodents, interval timing was delayed after administration of sulpiride (D2-receptor antagonist), quinpirole (D2-receptor agonist), and SCH-23390 (D1-receptor antagonist). By contrast, after administration of SKF-81297 (D1-receptor agonist), interval timing shifted earlier only in male rodents. These data illuminate sex similarities and differences in interval timing. Our results have relevance for rodent models of both cognitive function and brain disease by increasing representation in behavioral neuroscience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Lrp8 knockout mice fed a selenium-replete diet display subtle deficits in their spatial learning and memory function.

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Vaccine Attitudes and Uptake Among Latino Residents of a Former COVID-19 Hotspot.

Early in the COVID-19 pandemic, the Centers for Disease Control and Prevention identified Prince William County (PWC), Va. as a hotspot with a high disease rate among Latinos. This study uses spatial, survey, and qualitative data to understand attitudes towards vaccine uptake among PWC Latinos. A quantitative analysis (n=266) estimates the association for vaccine acceptance among Latinos. Next, qualitative interviews with Latinos (n=37) examine vaccine attitudes. Finally, a spatial analysis identifies clusters of social vulnerability and low vaccine uptake in PWC and adjacent counties. Our findings show that a substantial proportion of PWC Latinos had low vaccination rates as of December 2022, two years after the vaccine's release. Side effects and safety and approval concerns were cited in both the quantitative and qualitative studies. Persistent vaccine disparities are concerning given the high hospitalization and mortality rates that prevailed among Latinos early in the pandemic.

Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.

HELLP Syndrome at 20 Gestational Weeks Managed Using the Mississippi Protocol: A Case Report.

Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP syndrome occurring before 22 gestational weeks (GWs) is extremely rare, and patients prevalently exhibit underlying maternal diseases or fetal abnormalities. Here, we report the case of a pregnant woman who had HELLP syndrome at 20 GWs without any obvious underlying maternal diseases or fetal abnormalities. A 38-year-old pregnant woman was referred to Kobe University Hospital from another hospital at 19 + 5/7 GWs for hypertension, proteinuria, generalized edema, and fetal growth restriction. She was diagnosed with partial HELLP syndrome according to the Mississippi classification at 20 + 2/7 GWs. The patient was managed following the Mississippi protocol, including intravenous dexamethasone, magnesium sulfate, and antihypertensive drugs. She received intensive blood pressure and laboratory data monitoring using an arterial line and additional treatments, including platelet transfusion, intravenous haptoglobin infusion, and human atrial natriuretic peptide. The pregnancy ended in an induced delivery at 20 + 3/7 GWs, and she was discharged without complications 10 days postnatal. We performed laboratory tests for diagnosing underlying diseases but identified no obvious underlying diseases. This report indicates that early and intensive treatment of patients with HELLP syndrome occurring before 22 GWs according to the Mississippi protocol may enable clinicians to complete pregnancy termination without maternal complications and provide useful information to clinical practitioners in perinatal medicine.

[A Case of Stage â £ Gastric Cancer with Multiple Liver Metastases, Resected Primary Tumor after Chemotherapy, and Alive for 3.5 Years without Recurrence].

A 67-year-old man visited our hospital for epigastric pain. Esophagogastroduodenoscopy(EGD)revealed type 2 gastric cancer from the cardia to the gastric angle, and histopathological examination revealed papillary adenocarcinoma(pap), HER2-positive. Contrast-enhanced CT showed wall thickening mainly in the posterior wall of the gastric body, enlarged lymph nodes that were lumped together with the main lesion, and 8 low-absorption areas with ring shaped contrast effects in both lobes of the liver. The patient was diagnosed as gastric cancer cT4aN(+)M1[HEP], clinical Stage ⅣB. Six courses of capecitabine plus cisplatin plus trastuzumab(XP plus Tmab)therapy and 17 courses of capecitabine plus trastuzumab(X plus Tmab)therapy were performed. After chemotherapy, liver and lymph node metastases disappeared on CT and MRI. EGD showed residual gastric cancer, and the policy was to resect the primary tumor. Laparoscopic total gastrectomy with D2 lymph node dissection was performed. Pathological results showed T1b(SM)depth, no lymph node metastasis, and histologic response was Grade 2a. Six courses of X plus Tmab were administered as postoperative adjuvant chemotherapy, but were discontinued at the patient's request. Currently, 5 years have passed since the first chemotherapy and 3.5 years have passed since the surgery, and the patient is alive without recurrence, suggesting that the conversion surgery may have contributed to the prolonged survival.