HIV pre-exposure prophylaxis and opportunities for vaccination against hepatitis A virus, hepatitis B virus and human papillomavirus: an analysis of the Ontario PrEP cohort study.

OBJECTIVES: Populations who seek HIV pre-exposure prophylaxis (PrEP) are disproportionately affected by hepatitis A virus (HAV), hepatitis B virus (HBV) and human papillomavirus (HPV). We examined immunity/vaccination against these infections among participants in the Ontario PrEP cohort study (ON-PrEP). METHODS: ON-PrEP is a prospective cohort of HIV-negative PrEP users from 10 Ontario clinics. We descriptively analysed baseline immunity/vaccination against HAV (IgG reactive), HBV (hepatitis B surface antibody >10) and HPV (self-reported three-dose vaccination). We further performed multivariable logistic regression to identify characteristics associated with baseline immunity/vaccination. We used cumulative incidence functions to describe vaccine uptake among participants non-immune at baseline. RESULTS: Of 633 eligible participants, 59.1% were white, 85.8% were male and 79.6% were gay. We found baseline evidence of immunity/vaccination against HAV, HBV and HPV in 69.2%, 81.2% and 16.8% of PrEP-experienced participants and 58.9%, 70.3% and 10.4% of PrEP-naïve participants, respectively. Characteristics associated with baseline HAV immunity were greater PrEP duration (adjusted OR (aOR) 1.41/year, 95% CI 1.09 to 1.84), frequent sexually transmitted and bloodborne infection (STBBI) testing (aOR 2.38, 95% CI 1.15 to 4.92) and HBV immunity (aOR 3.53, 95% CI 2.09 to 5.98). Characteristics associated with baseline HBV immunity were living in Toronto (aOR 3.54, 95% CI 1.87 to 6.70) or Ottawa (aOR 2.76, 95% CI 1.41 to 5.40), self-identifying as racialised (aOR 2.23, 95% CI 1.19 to 4.18), greater PrEP duration (aOR 1.39/year, 95% CI 1.02 to 1.90) and HAV immunity (aOR 3.75, 95% CI 2.19 to 6.41). Characteristics associated with baseline HPV vaccination were being aged ≤26 years (aOR 9.28, 95% CI 2.11 to 40.77), annual income between CAD$60 000 and CAD$119 000 (aOR 3.42, 95% CI 1.40 to 8.34), frequent STBBI testing (aOR 7.00, 95% CI 1.38 to 35.46) and HAV immunity (aOR 6.96, 95% CI 2.00 to 24.25). Among those non-immune at baseline, overall cumulative probability of immunity/vaccination was 0.70, 0.60 and 0.53 among PrEP-experienced participants and 0.93, 0.80 and 0.70 among PrEP-naïve participants for HAV, HBV and HPV, respectively. CONCLUSIONS: Baseline immunity to HAV/HBV was common, and a sizeable proportion of non-immune participants were vaccinated during follow-up. However, HPV vaccination was uncommon. Continued efforts should be made to remove barriers to HPV vaccination such as cost, inclusion in clinical guidelines and provider recommendation.

Effects of duration of exposure, co-supplementation with iron and Nippostrongylus brasiliensis infection on accumulation of trichloroacetic acid-insoluble copper in rats given molybdate in drinking water.

Thiolation can convert molybdate (MoO4) into a series of thiomolybdates (MoSxO4-x) in the rumen, terminating in tetrathiomolybdate (MoS4), a potent antagonist of copper absorption and, if absorbed, donor of reactive sulphide in tissues. Systemic exposure to MoS4 increases trichloroacetic acid-insoluble copper (TCAI Cu) concentrations in the plasma of ruminants and induction of TCAI Cu in rats given MoO4 in drinking water would support the hypothesis that rats, like ruminants, can thiolate MoO4. Data on TCAI Cu are presented from two experiments involving MoO4 supplementation that had broader objectives. In experiment 1, plasma Cu concentrations (P Cu) tripled in female rats infected with Nippostrongylus brasiliensis after only 5 days exposure to drinking water containing 70 mg Mo L-1, due largely to an increase in TCAI Cu; activities of erythrocyte superoxide dismutase and plasma caeruloplasmin oxidase (CpOA) were unaffected. Exposure for 45-51 days did not raise P Cu further but TCA-soluble (TCAS) Cu concentrations increased temporarily 5 days post infection (dpi) and weakened the linear relationship between CpOA and TCAS Cu. In experiment 2, infected rats were given less MoO4 (10 mg Mo L-1), with or without iron (Fe, 300 mg L-1), for 67 days and killed 7 or 9 dpi. P Cu was again tripled by MoO4 but co-supplementation with Fe reduced TCAI Cu from 65 ± 8.9 to 36 ± 3.8 µmol L-l. Alone, Fe and MoO4 each reduced TCAS Cu in females and males when values were higher (7 and 9 dpi, respectively). Thiolation probably occurred in the large intestine but was inhibited by precipitation of sulphide as ferrous sulphide. Fe alone may have inhibited caeruloplasmin synthesis during the acute phase response to infection, which impacts thiomolybdate metabolism.

Development of an Automated Capillary Immunoassay to Detect Prion Glycotypes in Creutzfeldt-Jakob Disease.

Creutzfeldt-Jakob disease (CJD) comprises a group of transmissible neurodegenerative diseases with vast phenotypic diversity. Sporadic CJD heterogeneity is predominantly influenced by the genotype at codon 129 of the prion-encoding gene and the molecular weight of PrPSc fragments after protease digestion, resulting in a classification of 6 subtypes of CJD (MM1, MM2, MV1, MV2, VV1, and VV2). The majority of cases with CJD can be distinguished using this classification system. However, a number of reported CJD cases are phenotypically unique from others within their same subtype, such as variably protease-sensitive prionopathies, or exist as a mixture of subtypes within the same patient. Western blotting of brain tissue, along with the genotyping of codon 129 of the prion-encoding gene, is considered the "gold standard" for the biochemical characterization of CJD. Western blotting requires a significant amount of prion protein for detection, is labor-intensive, and is also associated with high interassay variability. In addition to these limitations, a growing body of research suggests that unique subtypes of CJD are often undetected or misdiagnosed using standard diagnostic western blotting protocols. Consequently, we successfully optimized and developed a capillary-based western assay using the JESS Simple Western (ProteinSimple) to detect and characterize prion proteins from patients with CJD. We found that this novel assay consistently differentiated CJD type 1 and type 2 cases with a limit of detection 10 to 100× higher than traditional western blotting. Cases with CJD in which type 1 and type 2 coexist within the same brain region can be detected using type 1-specific and type 2-specific antibodies, and we found that there was remarkable specificity for the detection of cases with variably protease-sensitive prionopathy. The assay presented displays outstanding sensitivity, allowing for the preservation of valuable samples and enhancing current detection methods.

Effects of Molybdate and Tetrathiomolybdate Supplementation of Drinking Water on Immature Rats Infected with Nippostrongylus brasiliensis. 2. Copper Status and Tissue Molybdenum Accretion.

Molybdate (MoO4) and tetrathiomolybdate (MoS4) supplementation of rats via drinking water had opposite effects on the establishment of Nippostrongylus brasiliensis larvae but both induced hypercupraemia, temporarily inhibited activities of superoxide dismutase in liver and duodenum after infection and enlarged the femoral head. Effects of MoO4 and MoS4 on activities of caeruloplasmin oxidase (CpO) in plasma, erythrocyte superoxide dismutase (ESOD) and tissue copper (Cu) and molybdenum (Mo) were compared to test the hypothesis that species lacking a rumen can thiolate MoO4. Three groups of 18 immature Wistar rats were given Mo (70 mg/L as MoO4) or MoS4 (5 mg/L) via drinking water or remained untreated; all received a commercial, cubed diet and 12 from each group were infected with larvae of N. brasiliensis. Rats were killed 7-9 days later and liver, kidney, spleen, heart, muscle (quadriceps), brain and bone (femur) removed for Cu and Mo analysis. Plasma Cu was greatly increased by MoO4 and MoS4, without changing CpO activity, but the effect was more variable with MoO4 and accompanied by a smaller decrease in ESOD. Tissue Cu and Mo were increased by MoS4 in all tissues examined except brain and bone, correlating with plasma Cu and with each other; relationships were strongest in spleen, followed by kidney. MoO4 also increased soft tissue Cu and Mo but increases were generally smaller than those induced by MoS4 and correlations between the two elements and with plasma Cu generally weaker. Since hypercupraemia and correlated increases in liver and kidney Cu and Mo are characteristic of systemic thiomolybdate (TM) exposure, we conclude that MoO4 was partially thiolated to give a different TM profile from that produced by MoS4. The pathophysiological significance of systemic exposure to di- and tri-TM merits investigation in non-ruminants as agents of chelation therapy and in ruminants as agents of short-lived TM toxicity on Mo-rich pastures.

Clinical Considerations in the Selection of Preexposure Prophylaxis for HIV Prevention in Canada.

According to the Public Health Agency of Canada, approximately 62,050 people were living with HIV in Canada in 2018, and of those, 13% were undiagnosed. Currently, no single strategy provides complete protection or is universally effective across all demographic groups at risk for HIV. However, HIV preexposure prophylaxis (PrEP) is the newest HIV prevention strategy that shows promise. To date, two products have received an indication for PrEP by Health Canada: emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) and emtricitabine/tenofovir alafenamide (Descovy®; FTC/TAF). Despite the high efficacy of these PrEP intervention methods, access to PrEP in Canada remains low. Identifying and addressing barriers to PrEP access, especially in high-risk groups, are necessary to reduce HIV transmission in Canada. While guidelines published by the Center for Disease Control and Prevention (CDC) include FTC/TAF information, the efficacy of FTC/TAF for PrEP has not yet been considered in Canada's clinical practice guidelines. Thus, the current paper reviews data regarding the use of FTC/TDF and FTC/TAF for PrEP, which may be useful for Canadian healthcare providers when counseling and implementing HIV prevention methods. The authors highlight these data in relation to various at-risk populations and review ongoing clinical trials investigating novel PrEP agents. Overall, FTC/TDF PrEP is effective for many populations, including men who have sex with men, transgender women, heterosexuals with partners living with HIV, and people who use drugs. While there is fewer data reported on the efficacy of FTC/TAF to date, recent clinical trials have demonstrated noninferiority of FTC/TAF in comparison to FTC/TDF. Notably, as studies have shown that FTC/TAF maintains renal function and bone mineral density to a greater extent than FTC/TDF, FTC/TAF may be a safer option for patients experiencing renal and/or bone dysfunction, for those at risk of renal and bone complications, and for those who develop FTC/TDF-related adverse events.

Effects of Chronic Exposure to Molybdate and Tetrathiomolybdate Supplementation of Water on Immature Rats Acutely Infected with Nippostrongylus brasiliensis. 1. Effects on Outcome of Infection and Host Health.

Low molybdate (MoO4) exposure via drinking water in mature rats infected with Nippostrongylus brasiliensis raised liver and plasma copper (Cu) concentrations. The possibility that anthelmintic effects were attributable to conversion of MoO4 to tetrathiomolybdate (MoS4) in a non-ruminant species was investigated by giving three groups of 18 immature rats drinking water containing 70 mg Mo l-1 as MoO4 (group A), 5 mg Mo l-1 as MoS4 (group B) or no supplement (group C), while receiving a commercial cubed diet. After 41 days, 12 rats from each group were inoculated subcutaneously with 2,000 L3-stage N. brasiliensis larvae. Subgroups were killed 7, 8 or 9 days post infection (dpi), when adult worms are normally expelled, and enzyme markers for the inflammatory response to infection were measured in plasma or liver. Male rats given MoS4 prior to infection grew more slowly than those given MoO4. Eight dpi, females given MoS4 had lost more bodyweight than those in group C, while those given MoO4 had gained weight. Mean worm counts at 7 dpi were 160, 65 and 250 ± 30.6 (SE), respectively, in groups C, A and B, and differed significantly from each other (P <0.05) but only rats given MoO4 remained infected 9 dpi (mean worm count 52 ± 16.4): Faecal egg counts followed a broadly similar pattern. Both Mo sources pre-empted increases in liver and duodenal superoxide dismutase activity, induced by infection 7 and 9 dpi, respectively, in group C and enlarged the femur: neither source prevented hypertrophy of the small intestine and a rise in serum mast cell protease concentration caused by infection. Since data for plasma Cu concentration and caeruloplasmin oxidase activity, reported separately, indicated MoO4 was thiolated in vivo, differences between Mo sources may be attributable to differences in the degree of thiolation, extent of thiomolybdate exposure and rates of thiomolybdate degradation at critical times in host or parasite development.

Effects of Raising or Lowering Molybdenum Status on Outcome of Acute Infection with Nippostrongylus brasiliensis in Mature Rats.

Molybdate (Mo+) supplements can suppress or enhance nematode infections in ruminants, depending on exposure level, but there have been no investigations in non-ruminants. Three groups of 16 mature rats were each fed a commercial diet and given Mo+ (10 mg Mo/l), tungstate (a molybdenum [Mo] antagonist) (MoO4, 350 mg W/l) or no supplement (C) via drinking water for 40 days before acute infection with 3,600 Nippostrongylus brasiliensis larvae. Group Mo- also received allopurinol (1 g/l), a molybdenoenzyme inhibitor, from 4 days post infection (dpi). Subgroups of four rats from each group were killed at 7-14 dpi. A group of six rats was left untreated and uninfected and subgroups killed 10 or 12 dpi. Infection reduced intakes of food and water but impacts were greatest in group Mo-. Median worm counts in groups C, Mo- and Mo+ were 900, 941 and 510, respectively, at 7 dpi and 9, 40 and 0 (P = 0.05) at 10 dpi. Median faecal egg counts were consistently lowest in group Mo+. Worm weight was reduced (P <0.05), worm tissue protease increased and superoxide dismutase activities increased in worm (P < 0.01) and host duodenal homogenates (P < 0.01) from group Mo+. In group Mo-, liver Mo concentration decreased, duodenal xanthine oxidoreductase activity (DXOR) became totally inhibited and plasma uric acid was barely detectable at 10 dpi. Plasma mast cell protease activity and duodenal malonyldialdehyde concentrations, markers of inflammation, were increased by nematode infection (P <0.001) but unaffected by water treatments. Liver Mo, liver copper (Cu) and plasma Cu concentrations were increased in group Mo+ and plasma Cu concentration was increased in group Mo- suggesting systemic exposure to partially thiolated MoO4 and WO4. Supplementary MoO4 impaired larval establishment and changed parasite biochemistry without affecting the inflammatory response to infection but may have required partial thiolation to do so. Rats did not rely on DXOR activity to expel N. brasiliensis.

"Lovesick": Mental Health and Romantic Relationships among College Students.

This research investigated the interpersonal impact of self-reported mental health diagnoses and/or perceptions on undergraduate students' current or most recent romantic relationship. Analysis of data from a 43-item online questionnaire completed by 267 undergraduates revealed that 68.3% of women and 52.5% of men reported having either been professionally diagnosed with a mental illness or perceive themselves to be mentally ill based on DSM criteria, with women and white students reporting significantly higher levels. Sociologically speaking, mental illness was found to influence relationship initiation, maintenance, and dissolution in this study. The mental health of the respondents' potential partners was an important consideration in deciding to form a relationship, particularly for male, white, heterosexuals. When the respondents reported relationship problems, men were more likely to blame such problems on mental health issues than women. Finally, though more respondents reported having broken up with a romantic partner who had mental health issues than had romantic partners break up with them, there were no significant gender, race, or sexual orientation differences in the termination of these romantic relationships. Study findings emphasize the importance of acknowledging and providing mental health resources-particularly interpersonal options-for emerging adults in the college setting.

Changes in renal and metabolic indices after switching from tenofovir disoproxil fumarate- to tenofovir alafenamide-containing ART among individuals with HIV in Canada: A retrospective study.

We assessed renal and metabolic changes associated with switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing regimens among patients with HIV at the Maple Leaf Medical Clinic, Toronto, Canada. Using an electronic medical records retrospective chart review from July 2005 to December 2019, 651 patients aged ≥16 years taking TDF-containing regimens for ≥6 months who switched to TAF-containing regimens for ≥6 months were included. Change in estimated glomerular filtration rate (eGFR) was examined at 12-month follow-up. Secondary outcomes included change in urine albumin-to-creatinine ratio, serum phosphate, alkaline phosphatase (ALP), cholesterol markers, HbA1C, and weight. After 12 months, eGFR increased in 63% of the baseline eGFR <60 mL/min/1.73 m2 group (mean change [SD] = +5.1 [10.8], p = 0.002), 52% for the baseline eGFR = 60-90 mL/min/1.73 m2 group (+0.5 [10.4], p = 0.490), and 26% for baseline eGFR >90 mL/min/1.73 m2 group (-7.2 [11.2], p <0.001). The multivariable generalized estimating equations model showed a significant reduction in eGFR after 12 months. Advanced age, HCV coinfection, and being switched to or on integrase inhibitors were significantly associated with reduced eGFR. Among secondary outcomes, ALP significantly decreased, while high-density lipoprotein, low-density lipoprotein, and weight significantly increased. Our findings suggest that TDF-to-TAF switching was beneficial for those with preexisting renal impairment (eGFR <60 mL/min/1.73 m2).

Decentralizing PrEP delivery: Implementation and dissemination strategies to increase PrEP uptake among MSM in Toronto, Canada.

Pre-exposure prophylaxis (PrEP) is traditionally prescribed by HIV specialist physicians. Given finite specialist resources, there is a need to scale up PrEP delivery by decentralizing services via other healthcare professionals. We aimed to assess the feasibility of delivering PrEP to men who have sex with men (MSM) through primary care physicians and sexual health clinic nurses. We piloted a multi-component, implementation and dissemination research program to increase provision of PrEP through primary care physicians and sexual health clinic nurses in Toronto, Canada. Community-based organizations (CBOs) provided prospective participants with information cards that contained links to an online module on engaging providers in a conversation about PrEP. In our patient-initiated continuing medical education (PICME) strategy, participants saw their family doctors and gave them the card, which also contained a link to a Continuing Medical Education module. In the nurse-led strategy, participants visited one of two participating clinics to obtain PrEP. We administered an optional online questionnaire to patients and providers at baseline and six months. CBOs distributed 3043 cards. At least 339 men accessed the online module and 196 completed baseline questionnaires. Most (55%) intended to visit nurses while 21% intended to consult their physicians. Among 45 men completing follow-up questionnaires at 6 months, 31% reported bringing cards to their physicians and obtaining PrEP through them; sexual health clinics delivered PrEP to 244 patients. Participants who went through the PICME approach reported no changes in relationships with their providers. Nurses showed fidelity to PrEP prescribing guidelines. Nurse-led PrEP and patient-initiated continuing medical education (PICME) for primary care physicians are feasible strategies to increase PrEP uptake. Nurse-led PrEP delivery was preferred by most patients.

"Thanks for Telling Me": The Impact of Disclosing Sex Secrets on Romantic Relationships.

This research investigated the relationship consequences of disclosing sexual secrets to a romantic partner. Analyses of data from a 39-item Internet questionnaire completed by 195 undergraduate students showed that revealing sex secrets to a romantic partner was associated with either neutral or positive relationship outcomes. Disclosure of sexual secrets almost never (< 5%) resulted in relationship dissolution and over a third of the sample reported that they appreciated the honest disclosure. In addition, keeping sex secrets was related to lower relationship satisfaction such that each additional sex secret being kept from a romantic partner was associated with a one-half point loss of satisfaction (on a 5-point relationship satisfaction scale). This decrease persisted when controlling for sex and race. Mediation analyses found support for the notion that the type of romantic relationship an individual is in explains part of the association between keeping secrets and relationship satisfaction. Implications and future research considerations are suggested.

Cardiovascular Events in an Inner-City HIV Clinic and Relationship to Abacavir Versus Tenofovir Disoproxil Fumarate-Containing Antiretroviral Regimens.

Following cardiovascular events (CVE) among people living with HIV (PLWH) is essential. Abacavir (ABC)'s impact on CVE challenges clinicians. We characterized CVE at our HIV clinic associated with ABC versus tenofovir disoproxil fumarate (TDF). This was a retrospective study of PLWH who started combination antiretroviral therapy with no prior CVE. Patients were evaluated as antiretroviral naive or antiretroviral experienced. Regimens included the following: always-ABC, always-TDF, first-ABC-switched-to-TDF, and first-TDF-switched-to-ABC regimens. Frequencies, rates, and Poisson regression were used to analyze CVE (cardiovascular/cerebrovascular) and were stratified with an a priori cutoff of before or after January 1, 2009. 1,440/2,852 patients were antiretroviral naive; 658 on always-ABC regimens, 1,186 on always-TDF regimens, 737 first-ABC-switched-to-TDF regimens, and 271 first-TDF-switched-to-ABC regimens. Seventy seven CVE occurred overall [16 naive vs. 61 experienced (p < .0001)]. Sixty events were cardiovascular and 17 cerebrovascular (p < .0001). Sixty-nine CVE occurred before 2009 and eight after (p < .0001). There were 5.65 CVE-per-1,000-years [95% confidence interval (CI) 3.23-9.87] in the always-ABC, 1.95 CVE-per-1,000-years (95% CI 1.08-3.51) in the always-TDF, 2.01 CVE-per-1,000-years (95% CI 1.14-3.56) in the ABC-switched-to-TDF, and 1.82 CVE-per-1,000-years (95% CI 0.77-4.30) in TDF-switched-to-ABC (p <.01). Multivariable Poisson regression incidence rate ratios (IRRs) revealed that being on ABC-only (IRR 2.89; 95% CI 2.13-3.94), age (IRR 1.06 per year; 95% CI 1.04-1.07), and smoking (IRR for current 2.81; 95% CI 1.97-3.99; IRR for former 2.49; 95% CI 1.72-3.61) increased risk of CVE. Thus, in our clinic, CVE rates were increased in those on ABC and adds to the body of literature suggesting concern.

Alcohol consumption, substance use, and depression in relation to HIV Pre-Exposure Prophylaxis (PrEP) nonadherence among gay, bisexual, and other men-who-have-sex-with-men.

BACKGROUND: Although HIV pre-exposure prophylaxis (PrEP) substantially diminishes the likelihood of HIV acquisition, poor adherence can decrease the HIV-protective benefits of PrEP. The present investigation sought to identify the extent to which alcohol consumption, substance use, and depression were linked to PrEP nonadherence among gay, bisexual, and other men-who-have-sex-with-men (gbMSM). METHODS: gbMSM (age ≥ 18, prescribed PrEP for ≥3 months) were recruited from two clinics in Toronto, Canada for an e-survey assessing demographics; PrEP nonadherence (4-day PrEP-focused ACTG assessment); hazardous and harmful alcohol use (AUDIT scores of 8-15 and 16+, respectively); moderate/high risk substance use (NIDA M-ASSIST scores > 4); depression (CESD-10 scores ≥10); and other PrEP-relevant factors. The primary outcome, PrEP nonadherence, entailed missing one or more PrEP doses over the past 4 days. A linear-by-linear test of association assessed whether increasing severity of alcohol use (i.e., based on AUDIT categories) was linked to a greater occurrence of PrEP nonadherence. Univariate logistic regression was employed to determine factors associated with PrEP nonadherence, and factors demonstrating univariate associations at the p < .10 significance level were included in a multivariate logistic regression model. Additive and interactive effects involving key significant factors were assessed through logistic regression to evaluate potential syndemic-focused associations. RESULTS: A total of 141 gbMSM (Mean age = 37.9, white = 63.1%) completed the e-survey. Hazardous/harmful drinking (31.9%), moderate/high risk substance use (43.3%), and depression (23.7%) were common; and one in five participants (19.9%) reported PrEP nonadherence. Increasing alcohol use level was significantly associated with a greater likelihood of nonadherence (i.e., 15.6, 25.0, and 44.4% of low-risk, hazardous, and harmful drinkers reported nonadherence, respectively (χ2(1) = 4.79, p = .029)). Multivariate logistic regression demonstrated that harmful alcohol use (AOR = 6.72, 95%CI = 1.49-30.33, p = .013) and moderate/high risk cocaine use (AOR = 3.11, 95%CI = 1.01-9.59, p = .049) independently predicted nonadherence. Furthermore, an additive association emerged, wherein the likelihood of PrEP nonadherence was highest among those who were hazardous/harmful drinkers and moderate/high risk cocaine users (OR = 2.25, 95%CI = 1.19-4.25, p = .013). Depression was not associated with nonadherence. CONCLUSIONS: Findings highlight the need to integrate alcohol- and substance-focused initiatives into PrEP care for gbMSM. Such initiatives, in turn, may help improve PrEP adherence and reduce the potential for HIV acquisition among this group.

Nontuberculous Mycobacterial Disease and Molybdenum in Colorado Watersheds.

Nontuberculous mycobacteria (NTM) are environmental bacteria that may cause chronic lung disease. Environmental factors that favor NTM growth likely increase the risk of NTM exposure within specific environments. We aimed to identify water-quality constituents (Al, As, Cd, Ca, Cu, Fe, Pb, Mg, Mn, Mo, Ni, K, Se, Na, Zn, and pH) associated with NTM disease across Colorado watersheds. We conducted a geospatial, ecological study, associating data from patients with NTM disease treated at National Jewish Health and water-quality data from the Water Quality Portal. Water-quality constituents associated with disease risk were identified using generalized linear models with Poisson-distributed discrete responses. We observed a highly robust association between molybdenum (Mo) in the source water and disease risk. For every 1- unit increase in the log concentration of molybdenum in the source water, disease risk increased by 17.0%. We also observed a statistically significant association between calcium (Ca) in the source water and disease risk. The risk of NTM varied by watershed and was associated with watershed-specific water-quality constituents. These findings may inform mitigation strategies to decrease the overall risk of exposure.

Assessment of antiretroviral third agent virologic durability after initiation of first antiretroviral regimen.

Information on the virologic durability of modern antiretroviral regimens is important to clinicians. We aimed to describe virologic durability of first-line integrase strand transfer inhibitor (INSTI)-, nonnucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based antiretroviral regimens. This was a retrospective study of antiretroviral-naïve patients that initiated first-line antiretroviral regimens with two nucleoside reverse transcriptase inhibitors and an INSTI, NNRTI, or PI between January 2006 and June 2016. The outcome was time to virologic failure, which was assessed by Kaplan-Meier survival analysis and Cox regression models. There were 780 patients (median age = 37 years [interquartile range (IQR) = 30-45], 93.3% male, 56.2% Caucasian, median HIV duration = 1.8 years [IQR = 0.4-5.4], baseline log10 viral load [VL]=4.6 [IQR = 4.1-5.1], and baseline CD4+ cell count = 320 cells/µl [IQR = 217-440]). In total, 189/780 were on a third agent INSTI, 339/780 on a third agent NNRTI, and 252/780 on a third agent PI. Kaplan-Meier survival probability revealed longer time to virologic failure for INSTI, followed by NNRTI then PI (p < 0.001). Multivariable Cox regression revealed that being on an INSTI regimen (aHR = 0.27; 95%CI = 0.18-0.41) or NNRTI regimen (aHR = 0.64; 95%CI = 0.47-0.87) versus PI regimen, frequent VL testing (per year), (aHR = 0.64; 95%CI = 0.47-0.87), and duration of ART (aHR = 0.22; 95%CI = 0.17-0.30) (years) were inversely associated with time to virologic failure, and log10 of baseline VL (aHR = 1.94; 95%CI = 1.58-2.39 per log10) increased risk. Virologic failure was delayed and virologic durability prolonged for INSTI- compared to NNRTI- and PI-based regimens, supporting current antiretroviral therapy guidelines.

Profile of gynaecology surgeries from Western Province, Solomon Islands.

INTRODUCTION: Evidence is lacking on the profile of gynaecological conditions affecting women in the Solomon Islands, including the availability and quality of surgical management. METHODS: Prospective analysis of hospital records was undertaken on all patients who underwent gynaecological surgery at Gizo Hospital, Western Province during a 6-day program led by volunteer Australian surgeons. Patient data on pre-operative history, investigation results, performed surgical procedures and postoperative recovery were collected. RESULTS: Of the 23 patients who presented with gynaecological problems requiring surgery, 20 underwent at least one surgical procedure during the study period. The most common presenting symptoms were pain and abnormal uterine bleeding. Median body mass index was 27, and 70% of patients were overweight or obese. Two surgeries were cancelled due to dengue fever. The surgeries performed were 12 vaginal operations, 8 laparoscopies and 9 laparotomies. Of surgical specimens collected, 61% were sent for histopathology testing. The median duration of postoperative hospital admission was 2 days (interquartile range, 1 day). CONCLUSION: The Solomon Islands presents a unique profile of challenges to surgical practice, including the impact of dengue infection on fitness for surgery, a mobile patient population dispersed across the islands, difficult access to pathology services, and increased length of stay. Despite this, most patients had surgical outcomes equivalent to those in a developed setting.

Decentralizing the delivery of HIV pre-exposure prophylaxis (PrEP) through family physicians and sexual health clinic nurses: a dissemination and implementation study protocol.

BACKGROUND: Gay, bisexual and other men who have sex with men (gbMSM) in Canada continue to experience high rates of incident HIV. Pre-exposure prophylaxis (PrEP, the regular use of anti-HIV medication) reduces HIV acquisition and could reduce incidence. However, there are too few physicians with expertise in HIV care to meet the projected demand for PrEP. To meet demand and achieve greater public health impact, PrEP delivery could be 'decentralized' by incorporating it into front-line prevention services provided by family physicians (FPs) and sexual health clinic nurses. METHODS: This PrEP decentralization project will use two strategies. The first is an innovative knowledge dissemination approach called 'Patient-Initiated CME' (PICME), which aims to empower individuals to connect their family doctors with online, evidence-based, continuing medical education (CME) on PrEP. After learning about the project through community agencies or social/sexual networking applications, gbMSM interested in PrEP will use a uniquely coded card to access an online information module that includes coaching on how to discuss their HIV risk with their FP. They can provide their physician a link to the accredited CME module using the same card. The second strategy involves a pilot implementation program, in which gbMSM who do not have a FP may bring the card to designated sexual health clinics where trained nurses can deliver PrEP under a medical directive. These approaches will be evaluated through quantitative and qualitative methods, including: questionnaires administered to patients and physicians at baseline and at six months; focus groups with patients, FPs, and sexual health clinic staff; and review of sexual health clinic charts. The primary objective is to quantify the uptake of PrEP achieved using each decentralization strategy. Secondary objectives include a) characterizing barriers and facilitators to PrEP uptake for each strategy, b) assessing fidelity to core components of PrEP delivery within each strategy, c) measuring patient-reported outcomes including satisfaction with clinician-patient relationships, and d) conducting a preliminary costing analysis. DISCUSSION: This study will assess the feasibility of a novel strategy for disseminating knowledge about evidence-based clinical interventions, and inform future strategies for scale-up of an underutilized HIV prevention tool.

Characterisation of proteins in excretory/secretory products collected from salmon lice, Lepeophtheirus salmonis.

BACKGROUND: The salmon louse, Lepeophtheirus salmonis, is an ectoparasitic copepod which feeds on the mucus, skin and blood of salmonid fish species. The parasite can persist on the surface of the fish without any effective control being exerted by the host immune system. Other ectoparasitic invertebrates produce compounds in their saliva, excretions and/or secretions which modulate the host immune responses allowing them to remain on or in the host during development. Similarly, compounds are produced in secretions of L. salmonis which are thought to be responsible for immunomodulation of the host responses as well as other aspects of crucial host-parasite interactions. METHODS: In this study we have identified and characterised the proteins in the excretory/secretory (E/S) products of L. salmonis using LC-ESI-MS/MS. RESULTS: In total 187 individual proteins were identified in the E/S collected from adult lice and pre-adult sea lice. Fifty-three proteins, including 13 serine-type endopeptidases, 1 peroxidase and 5 vitellogenin-like proteins were common to both adult and pre-adult E/S products. One hundred and seven proteins were identified in the adult E/S but not in the pre-adult E/S and these included serine and cysteine-type endopeptidases, vitellogenins, sphingomyelinase and calreticulin. A total of 27 proteins were identified in pre-adult E/S products but not in adult E/S. CONCLUSIONS: The assigned functions of these E/S products and the potential roles they play in host-parasite interaction is discussed.