Perspectives on long-acting formulations of pre-exposure prophylaxis (PrEP) among men who have sex with men who are non-adherent to daily oral PrEP in the United States.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. RESULTS: Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. CONCLUSION: Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.

Adherence to Daily Oral TDF/FTC for PrEP in Community Health Center Populations: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) Study.

The prevention effectiveness of oral preexposure prophylaxis (PrEP) is highly dependent on medication adherence but no validated longer term PrEP adherence measures are readily available for use by primary care clinicians caring for diverse populations. We compared two self-report measures (number of doses missed in past 7 days and day-by-day past week pill taking) to results of tenofovir concentrations in dried blood spot (DBS) samples at quarterly visits over the first 12 months of PrEP use. 1420 men and women in five US community health centers enrolled in a medication adherence substudy. For 3, 6, 9 and 12 months, the respective percentages of persons with self-report vs DBS levels consistent having taken all 7 doses in the week prior were 71% (51%), 70% (47%), 71% (46%) and 69% (44%). Conversely, the percentage of participants reporting taking 0-1 doses in the week prior by self-report vs DBS drug levels at 3, 6, 9 and 12 months consistent with this level of nonadherence of 6% (9%), 5% (10%), 8% (9%), and 9% (15%). The estimated risk of low adherence (estimated 0-1 doses in the week prior) was higher for participants of Black (RR 1.60, CI 1.09-2.34) or "Other" race (RR 1.62, CI 0.99-2.65) compared with participants of White race; being a transgender female (RR 2.31, CI 1.33-4.02) compared to men who have sex with men; or enrollment at a study site with less experience in the provision of PrEP. The estimated risk of low adherence by DBS was lower for participants with a higher number of sex partners in the past 3 months and those having a bachelor's degree or higher. More work is needed to provide clinicians with measures to assess medication adherence in diverse US populations being prescribed PrEP to support its effective use in reducing HIV acquisition in individuals and at the community level.

Facilitators for retaining men who have sex with men in pre-exposure prophylaxis care in real world clinic settings within the United States.

BACKGROUND: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings. METHODS: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence. RESULTS: Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief). DISCUSSION: In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health.

Laparoscopic vs open approach for acute cholecystitis in octogenarians. A prospective multicenter observational nationwide study.

BACKGROUND: The world population is aging, with octogenarians expected to reach over 400 million by 2050. Acute cholecystitis is a serious complication in the elderly. Age is not a contraindication for emergency cholecystectomy, an option that can both save lives and preserve quality of life. METHODS: The present study aimed to compare open and laparoscopic surgical approaches. Over six months, 38 emergency surgery units enrolled all consecutive octogenarians with acute cholecystitis undergoing cholecystectomy. Postoperative outcomes were compared after propensity score matching analysis. RESULTS: The study included 212 patients (84 years [81-86], 47.2% women). The open approach was used in 32.1% of patients, and the laparoscopic approach in 67.9%. After propensity score matching, a decrease in hospital stays (open, 8 days [6-13]; laparoscopic, 5 days [4-8]; P < .001), 30-day morbidity (open, 48.5%; laparoscopic, 26.5%; P = .01), and 30-day mortality (open, 13.2%, laparoscopic, 1.5%; P = .02) was found. Among the specific postoperative complications, a decrease in septicemia (open, 14.7%; laparoscopic, 0%; P = .001) was observed. CONCLUSIONS: Laparoscopic approach was used in two out of three octogenarians. After propensity score matching, octogenarians undergoing laparoscopic approach had shorter length of hospital stay, fewer 30-day postoperative complications, fewer episodes of septicemia, and less 30-day mortality than octogenarians undergoing open approach. These findings suggest that the laparoscopic approach may be the preferred choice for octogenarians with acute cholecystitis undergoing cholecystectomy.

Prediction of peritoneal soiling in acute appendicitis with simple clinical and laboratory data. Prospective, multicenter, cohort study of 2,645 adult patients nationwide.

BACKGROUND AND AIMS: In order to facilitate the preoperative prediction of complicated appendicitis, we propose a complementary approach by selecting an endpoint defined by the intraoperative finding of peritoneal soiling (PS). METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending emergency general surgery patients on a 24-h, 7-days a week basis, enrolled consecutive adult patients requiring appendectomy. Patients were stratified according to the absence or the finding of PS during the surgical procedure. RESULTS: A total of 2645 patients were included; median age (IQR) was 35 (22-51) years, 44.3% were female. The laparoscopic approach was used in 70.8% of appendectomies. In a third of patients (31.7%), there was PS with pus around the appendix, or bowel contents, free pus, or blood in the peritoneal cavity. To develop the prediction model, 1764 patients were randomly selected for the derivation cohort and the remaining 881 patients were assigned to the validation cohort. On multivariable logistic regression analysis of all patients, two clinical variables (age, and pulse) and three laboratory variables (serum urea, serum sodium, and white blood cell count) were individually associated (P < .05) with a greater probability of having PS (Hosmer-Lemeshow chi, 1.63; P = .99; C-statistic, 0.7). Based on the multivariable regression model, both static and dynamic nomograms were developed for the prediction of PS in patients with acute appendicitis. CONCLUSIONS: The entry of simple clinical and laboratory variables in the dynamic nomogram may be useful in guiding the initial management of patients with acute appendicitis in resource-limited settings.

Characterization and application of a coating of starch extracted from avocado (Persea americana L. cv. Hass) seeds as an alternative to reduce acrylamide content in French fries.

The starch extracted from avocado (Persea americana L. cv. Hass) seeds was characterized and used in the preparation of an edible coating to reduce the oil uptake and acrylamide content in French fries. Starch characterization was carried out using Differential Scanning Calorimetry, Fourier transform infrared spectrophotometry, gelatinization, and scanning electron microscopy. Uncoated (UFF) and coated (CFF) French fries were compared and evaluated for moisture, water activity (Aw), fat, color, firmness, acrylamide content, and sensorial analysis. The extracted starch presented a high crystalline structure and good stability to mechanical work and heat treatments. The CFF French fries showed significantly higher Aw, color parameter a*, but lower luminosity and acrylamide content than UFF samples. Similarly, the CFF samples tended to decrease the fat content, although without statistical differences. Avocado seed starch can be an economical and technically feasible alternative to the food industry as an effective coating to reduce acrylamide content in French fries.

Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

Screening for chronic kidney disease in the ambulatory HIV population.

BACKGROUND: In 2005, the Infectious Disease Society of America published a guideline recommending that all patients with human immunodeficiency virus (HIV) be screened for kidney disease. We initiated a screening program for kidney disease in a dedicated HIV clinic that follows 1,631 patients. METHODS: The screening consisted of a serum creatinine, an estimated glomerular filtration rate (eGFR) as defined by the abbreviated Modification of Diet in Renal Disease equation, and a standard urinalysis for proteinuria. Subjects were identified as having a positive screen if they had 1+ proteinuria or greater on a standard urinalysis or an eGFR of less than 60 ml/min/ 1.73 m2. After 1 year of screening, a retrospective chart review was conducted to determine the efficacy of screening. Bivariate associations were assessed for each outcome. A multiple logistic regression analysis was conducted first with main effects models and then for all variables and interactions. RESULTS: 941 subjects that did not have previously documented chronic kidney disease were screened and 96 (10.2%) met the definition of CKD. 9% of subjects had proteinuria and 2.4% had a qualifying eGFR. In multivariate analysis diabetes, hypertension, and low CD4 count (< 200 cells per mm3), low viral load (< 400 copies/ml) displayed strong associations with proteinuria. In the case of reduced eGFR, diabetes and age retained strong associations while the association with hypertension had borderline significance. CONCLUSION: This study emphasizes the potential of similar screening programs to identify early or mild CKD in an ambulatory population of patients with HIV.

Is celiac disease better identified through HLA-DQ8 than through HLA-DQ2 in Mexican subjects? / ¿Es posible una mejor identificación de la enfermedad celiaca en sujetos mexicanos por medio de HLA-DQ8 que de HLA-DQ2?

INTRODUCTION AND AIMS: A strong genetic association between celiac disease (CD) and the human leukocyte antigen (HLA) has been widely demonstrated. In Europe, the HLA-DQ2 allele is predominant. However, studies in Latin America indicate that HLA-DQ8 could be more frequent. In Mexico, the frequency of those alleles has not been reported in subjects with CD. Therefore, the aim of the present study was to evaluate the distribution of HLA-DQ2 and HLA-DQ8 in Mexican individuals with CD. MATERIAL AND METHODS: An exploratory study was conducted on a cohort of 49 subjects with chronic diarrhea. Autoantibodies for CD, duodenal atrophy, and HLA haplotypes were determined. RESULTS: Thirty individuals had CD (23 women, mean age 54.2 ± 15.5 years), 24 (80%) of whom expressed HLA-DQ8, 15 (50%) expressed HLA-DQ2, and 11 (37%) presented with both alleles. However, neither the HLA-DQ2 nor the HLA-DQ8 allele was found in 5 (10%) individuals. In subjects with chronic diarrhea that did not have CD, 12 (63%) presented with HLA-DQ2, and 7 (37%) with HLA-DQ8. Individuals with CD expressed the combinations of the HLA-DQ8/DQ2 alleles (37 vs. 5%) and the HLA-DR4/DQ8 alleles (60 vs. 26%) more frequently than the subjects without CD. CONCLUSIONS: In Mexican subjects with CD, HLA-DQ8 distribution was more frequent than that of HLA-DQ2, indicating a possible similarity to the frequency reported in other Latin American countries. However, given the nature of the present study and its sample size, further conclusions could not be reached.

Donitriptan, but not sumatriptan, inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors.

BACKGROUND AND PURPOSE: It has been suggested that during a migraine attack capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception; hence, trigeminal inhibition may prevent this vasodilatation and abort migraine headache. This study investigated the effects of the agonists sumatriptan (5-HT(1B/1D) water-soluble), donitriptan (5-HT(1B/1D) lipid-soluble), PNU-142633 (5-HT(1D) water-soluble) and PNU-109291 (5-HT(1D) lipid-soluble) on vasodilator responses to capsaicin, alpha-CGRP and acetylcholine in dog external carotid artery. EXPERIMENTAL APPROACH: 59 vagosympathectomized dogs were anaesthetized with sodium pentobarbitone. Blood pressure and heart rate were recorded with a pressure transducer, connected to a cannula inserted into a femoral artery. A precalibrated flow probe was placed around the common carotid artery, with ligation of the internal carotid and occipital branches, and connected to an ultrasonic flowmeter. The thyroid artery was cannulated for infusion of agonists. KEY RESULTS: Intracarotid infusions of capsaicin, alpha-CGRP and acetylcholine dose-dependently increased blood flow through the carotid artery. These responses remained unaffected after intravenous (i.v.) infusions of sumatriptan, PNU-142633, PNU-109291 or physiological saline; in contrast, donitriptan significantly attenuated the vasodilator responses to capsaicin, but not those to alpha-CGRP or acetylcholine. Only sumatriptan and donitriptan dose-dependently decreased the carotid blood flow. Interestingly, i.v. administration of the antagonist, SB224289 (5-HT(1B)), but not of BRL15572 (5-HT(1D)), abolished the inhibition by donitriptan. CONCLUSIONS AND IMPLICATIONS: Our results suggest that the inhibition produced by donitriptan of capsaicin-induced external carotid vasodilatation is mainly mediated by 5-HT(1B), rather than 5-HT(1D), receptors, probably by a central mechanism.

Decrease in plasma levels of vasoactive intestinal polypeptide in short bowel syndrome: experimental study.

To investigate the behaviour of the vasoactive intestinal polypeptide (VIP) in short bowel syndrome (SBS), an experimental model of massive intestinal resection (MIR) was developed. For this purpose, 20 'minipigs' were divided into two experimental groups: A (control) and B (MIR). The parameters determined were the mean plasma levels of VIP and the degree of steatorrhea at four different times: T1 (basal), T2 (one week after surgery), T3 (two weeks after surgery), and T4 (24 weeks after surgery). The results indicated that, after MIR, a progressive decrease in the mean plasma levels of VIP takes place, with statistical significance in T3 (p < 0.05) and T4 (p < 0.01). This situation seems to be a direct result of the massive loss of intestinal tissue, and could lead to the use of this peptide to mark the evolution of the intestinal adaptation process.

[Takotsubo syndrome. Usefulness of nuclear medicine studies]. / Síndrome de Takotsubo. Utilidad de los estudios de Medicina Nuclear.

Takotsubo syndrome can mimic an acute myocardial infarction. It is characterized by anginal chest pain with ST elevation in precordial leads, no coronary obstruction on angiography, and typical and reversible deformation of the left ventricular due to antero-apical ballooning with basal hyperkinesis. The pathophysiology of this syndrome is uncertain. It is probably multifactorial, cardiac adrenergic nervous dysfunction standing out in the acute phase. We report two cases performed within the diagnostic context of Takotsubo syndrome. Cardiac SPECT was performed using (123)I Metaiodobenzylguanidine (MIBG) and (99m)Tc-Tetrofosmin and the results of two cases were adrenergic denervation in the anterior wall without alterations in myocardial perfusion study. Identification of Takotsubo syndrome is of clinical importance because its management and prognosis differ significantly from that of acute myocardial infarction.