The intestinal parasite Cryptosporidium is a common cause of chronic diarrhoea in AIDS patients and is responsible for significant morbidity and mortality. No effective treatment is currently ...available for this condition. Here we aim to determine the safety, tolerance, and clinical effect of letrazuril in the treatment of AIDS-related Cryptosporidiosis.
A prospective, open-label study of letrazuril was performed.
The study was conducted at the Immune Deficiency Treatment Centre (IDTC) of Montreal General Hospital, a tertiary-care centre with inpatient and outpatient facilities.
All HIV-positive patients presenting to the IDTC between November 1991 and January 1993 who had symptomatic intestinal Cryptosporidiosis were enrolled in this protocol. Sixteen participants entered the study and 15 were available for evaluation, having completed at least 2 weeks on the study medication.
Patients received letrazuril daily in escalating doses of 50 to 100 mg orally for 6 weeks. Clinical and laboratory evaluations were performed weekly during the treatment phase, with a follow-up evaluation 4 weeks after the end of this phase, for a total study period of 10 weeks.
Response to letrazuril was assessed by eradication of Cryptosporidial oocysts from the stool and symptomatic improvement in diarrhoea and abdominal pain. Haematological, biochemical, and electrocardiographic parameters were also studied to evaluate potential toxicities of the treatment.
Fourteen evaluable patients had baseline CD4 lymphocyte counts ranging from 3 to 99 x 10(6)/l cells (mean, 30 x 10(6)/l cells). (The fifteenth evaluable patient had a CD4 count 235 x 10(6)/l.) Of these 14 patients, five showed a major response (symptomatic improvement and eradication of Cryptosporidial oocysts from the stool), two had a minor response (symptomatic improvement with persistence of oocysts in stool), and seven had no response to therapy with letrazuril. Seven patients developed a transient drug-related rash.
Fifty per cent of the AIDS patients in this study experienced an improvement in their Cryptosporidial disease while receiving letrazuril. No serious dose-related toxicities were observed. Larger Phase II trials are needed to evaluate the safety and efficacy of letrazuril in AIDS-associated intestinal Cryptosporidiosis.
Abstract Background and aims There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular ...disease. However, whether and how these interact is not clear. Methods We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. Results PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. Conclusions Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk.
Coronavirus disease 2109 (COVID-19) vaccines have recently been approved to curb the global pandemic. The risk of allergic reactions to the vaccine polyethylene glycol (PEG) component has raised ...significant public concern. Desensitization is suggested in cases of vaccine related hypersensitivity reactions. After comprehensive literature review on the topic, our aim was to establish a safe and effective desensitization protocol for patients with suspected or confirmed immediate type hypersensitivity reactions to the COVID-19 vaccine.
Participants were referred to the McGill University Health Center (MUHC) Allergy-Immunology department for clinical evaluation following a reported reaction to their first dose of Moderna® mRNA-1273 or Pfizer-BioNTech® BNT162b2 vaccines. They underwent skin prick testing (SPT) with higher and lower molecular weight (MW) PEG and polysorbate 80, as per published protocols. Their second dose was administered following a desensitization protocol consisting of multiple dose-administration steps followed by a 60-min observation period.
Among a cohort of 142 patients with an increased risk for allergic reactions to the COVID-19 vaccines, six individuals were selected to undergo desensitization. All were female with allergic background including chronic spontaneous urticaria, anaphylaxis to medications, and/or vaccines. The main symptom after their first dose was difficulty swallowing with lightheadedness or immediate urticaria, angioedema, and/or dizziness. Two patients had positive skin testing. One patient was on chronic antihistamines which resulted in an inconclusive PEG skin test and the skin testing was negative for the three other patients. During the desensitization, two patients reported cutaneous symptoms of an immediate reaction and were managed with antihistamines. One of these patients also complained of ear pressure and had a drop in her systolic blood pressure, treated with intravenous fluids.
This study suggests that some individuals with an immediate-type hypersensitivity reaction to their first dose of mRNA COVID-19 vaccine may safely receive their second dose using a desensitization protocol. The success of this desensitization protocol is a step forward in the fight against COVID-19, allowing more individuals to be immunized.
Messenger RNA coronavirus disease 2019 (COVID-19) vaccines have been associated with allergic reactions. A history of anaphylaxis has been suggested as a risk factor for such reactions. Polyethylene ...glycol (PEG) has been proposed as a possible culprit allergen.
To investigate possible PEG or polysorbate allergy among patients reporting prior reactions to COVID-19 vaccines or PEG and to report their subsequent tolerance of COVID-19 vaccines.
From January 1, 2021, to October 31, 2021, adult patients referred to the McGill University Health Centre allergy clinics who were considered at risk of anaphylaxis were prospectively recruited. The entry criteria were any documented history of reaction to a COVID-19 vaccine or reported allergy to PEG or polysorbate. Evaluated patients underwent skin prick testing (SPT) with PEG and polysorbate. After SPT, placebo-controlled vaccine challenges were carried out.
Of the 44 patients recruited, 40 (90.1%) had reacted to the first vaccine dose, with 18 (45%) of them had anaphylactic reaction. All patients underwent SPT and 5 (11.3%) had a positive test result. A total of 39 patients (88.6%) underwent COVID-19 vaccine challenge at the allergy clinic. Most tolerated the vaccine, with 18 (40.1%) received a single full dose, 20 (45.4%) 2 split doses, and 6 (13.6%) a graded dosing protocol. Of the 40 patients who reacted to the first dose, 2 had immediate nonsevere allergic reactions to the second dose.
In this cohort of patients with a history of anaphylaxis and increased risk of allergic reactions to the COVID-19 vaccines, after allergist evaluation, including negative PEG skin testing result, the vaccine was safely administered without any serious adverse events.
Advances in metabolism Tsoukas, Michael A; Farr, Olivia M; Mantzoros, Christos S
Metabolism, clinical and experimental,
12/2013, Volume:
62, Issue:
12
Journal Article
In previous studies we have shown that removal of the spleen in HIV-infected people during the asymptomatic phase of disease results in slower time to AIDS and may also result in improved survival. ...In this paper, we examine whether splenectomy affects lymphocyte counts, T-cell subsets, and HIV plasma viremia in a manner that could explain the clinical benefits associated with this intervention.
10 HIV-infected patients who underwent splenectomy and 23 HIV-infected controls with idiopathic thrombocytopenia purpura who did not undergo splenectomy were studied. These groups were compared for changes in cell subpopulations and HIV plasma viremia.
Splenectomy resulted in increases in absolute lymphocyte numbers with rises in both CD4 and CD8 counts, whereas CD4 and CD8 percentage levels remained unchanged. In controls, absolute and percentage CD4+ T-cell counts declined with time from date of HIV infection. Plasma viremia decreased more than threefold, the limit of biologic variation, after splenectomy in 4 of 9 subjects and in only 1 of 18 controls. The proportion of subjects exhibiting reduced viremia following splenectomy was greater than that in HIV-infected patients that did not undergo splenectomy (chi 2 test, P = .015).
Improved survival and time to AIDS in splenectomized HIV-infected patients is associated with temporary reduction of plasma viremia and increase in absolute CD4 and CD8 counts. These effects could not be attributed to antiretroviral therapy because subjects were either untreated or treated with antiretroviral monotherapy during the observation period. These observations may have importance in the understanding of T-cell dynamics and the potential for splenectomy as an HIV reservoir-debulking procedure.
Objectives
Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol.
Methods
CHACS is ...a multi‐centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow‐up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender—gender roles, gender identity, gender relationships, and institutionalized gender—will be measured using the GENESIS‐PRAXY questionnaire. Diet will be assessed using a validated, web‐based, self‐administered food frequency questionnaire.
Results
A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50–61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail.
Conclusions
The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio‐economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses.
Background and Aims
Identifying typologies of social determinants of health (SDoH) vulnerability influencing drug use practices among women living with HIV (WLWH) can help to address associated ...harms. This research aimed to explore the association of SDoH clusters with drug use among WLWH.
Design
Latent class analysis (LCA) was used to identify the distinct clusters of SDoH. Inverse probability weighting (IPW) was employed to account for confounding and potential selection bias. Associations were analyzed using generalized linear model with log link and Poisson distribution, and then weighted risk ratio (RR) and 95% confidence intervals (CI) were reported.
Setting and Participants
Data from 1422 WLWH recruited at time‐point 1 of the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS, 2013–15), with 1252 participants at 18 months follow‐up (time‐point 2).
Measurements
Drug use was defined as use of illicit/non‐prescribed opioids/stimulants in the past 6 months. SDoH indicators included: race discrimination, gender discrimination, HIV stigma, social support, access to care, food security, income level, employment status, education, housing status and histories of recent sex work and incarceration.
Findings
LCA identified four SDoH classes: no/least SDoH adversities (6.6%), discrimination/stigma (17.7%), economic hardship (30.8%) and most SDoH adversities (45.0%). Drug use was reported by 17.5% and 17.2% at time‐points 1 and 2, respectively. WLWH with no/least SDoH adversities were less likely to report drug use than those in economic hardship class (weighted RR = 0.13; 95% CIs = 0.03, 0.63), discrimination/stigma class (weighted RR = 0.15; 95% CIs = 0.03, 0.78), and most SDoH adversities class (weighted RR = 0.13; 95% CIs = 0.03, 0.58).
Conclusions
Social determinants of health vulnerabilities are associated with greater likelihood of drug use, underscoring the significance of addressing interlinked social determinants and drug use through the course of HIV care and treatment.
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