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1.
J Pediatr ; 270: 114018, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38508485

ABSTRACT

OBJECTIVE: To investigate the role of early antiretroviral therapy (ART) on growth trajectories of infants with human immunodeficiency virus (IHIV) in the first year of life. STUDY DESIGN: As part of a clinical trial of early ART in Johannesburg, South Africa (2015-2018), 116 IHIV diagnosed within 48 hours of birth were started on ART as soon as possible, and 80 uninfected infants born to mothers living with HIV (IHEU) were enrolled. Both groups were followed prospectively from birth through 48 weeks and growth parameters collected. The groups were compared and risk factors for poor growth investigated, in the full cohort and among IHIV separately. RESULTS: IHIV had lower mean weight-for-age Z-scores (WAZ) than IHEU at 4 and 8 weeks (-1.17 [SE:0.14] vs -0.72 [0.14], P = .035 and -1.23 [0.15] vs -0.67 [0.14], P = .012). Although there was some closing of the gap over time, means remained lower in IHIV through 48 weeks. In length-for-age Z-scores (LAZ), differences widened over time and IHIV had lower Z-scores by 48 weeks (-1.41 [0.15] vs -0.80 [0.18], P = .011). Deficits in WAZ and LAZ in IHIV vs IHEU were most marked among girls. IHIV with pre-ART viral load ≥1000 copies/ml had significantly lower weight-for-length and mid-upper arm circumference Z-scores across all time points through 48 weeks. CONCLUSIONS: IHIV on early ART had deficits in WAZ over the first 8 weeks of life and lower LAZ at 48 weeks than IHEU. Among IHIV, higher pre-ART viral load was associated with worse anthropometric indicators through 48 weeks.


Subject(s)
HIV Infections , Humans , HIV Infections/drug therapy , Female , Infant , Male , Infant, Newborn , South Africa , Prospective Studies , Infectious Disease Transmission, Vertical/prevention & control , Child Development/drug effects , Pregnancy , Anti-Retroviral Agents/therapeutic use , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Anti-HIV Agents/therapeutic use , Body Weight
2.
AIDS Care ; 35(3): 334-340, 2023 03.
Article in English | MEDLINE | ID: mdl-34930060

ABSTRACT

Disclosure to children living with HIV (CLHIV) about their own status is associated with positive outcomes such as treatment adherence, but prior cross-sectional studies in sub-Saharan Africa report disclosure rates of <50%. This study aims to assess pediatric disclosure over time. 548 CLHIV were followed from 2/2013-4/2018 in Johannesburg, South Africa. Cumulative incidence of disclosure was calculated with Kaplan-Meier analysis, and disclosure characteristics assessed with a Cox model. By end of follow-up, cumulative disclosure was 70.3% (95% confidence interval: 60.0-79.9). Median age at disclosure was 9 years (range: 3-13). Baseline predictors of disclosure included older child age and the child having a history of going hungry. Prior to disclosure, 98.0% of caregivers who disclosed had conversed with their child about their illness or an HIV-related topic, or their child had asked about HIV, versus 88.6% of caregivers who never disclosed. While many children did not receive disclosure during this relatively large, longitudinal study of South African CLHIV, caregivers who had not yet disclosed may have been preparing to do so by discussing their child's health or HIV generally with their child. This highlights the need for clinicians to consistently support caregivers throughout the incremental disclosure process.


Subject(s)
Disclosure , HIV Infections , Humans , Child , Adolescent , Child, Preschool , South Africa/epidemiology , Longitudinal Studies , HIV Infections/epidemiology , Cross-Sectional Studies , Truth Disclosure , Caregivers
3.
Addict Biol ; 28(10): e13325, 2023 10.
Article in English | MEDLINE | ID: mdl-37753563

ABSTRACT

Relapse to oxycodone seeking progressively increases after abstinence in rats, a phenomenon termed incubation of oxycodone craving. We have previously shown that the orbitofrontal cortex (OFC) plays a critical role in incubation of oxycodone craving in male rats. Here, we examined the effect of oestrous cycle on incubated oxycodone seeking in female rats, and whether the critical role of OFC in incubated oxycodone seeking generalizes to female rats. We first assessed oxycodone self-administration and incubated oxycodone seeking on abstinence day 15 across the oestrous cycle. Next, we determined the effect of chemogenetic inactivation of OFC by JHU37160 (J60), a novel agonist for Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), on incubated oxycodone seeking on abstinence day 15. Finally, we determined the effect of J60 alone on incubated oxycodone seeking on abstinence day 15. We found no difference in oxycodone intake across oestrus, pro-oestrus, and metoestrus stages during oxycodone self-administration training. Incubated oxycodone seeking was also similar between nonoestrus and oestrus female rats. Moreover, chemogenetic inactivation of OFC by J60 decreased incubated oxycodone seeking on abstinence day 15, while J60 alone had no effect on incubated oxycodone seeking in no-DREADD control rats. Taken together, results here show that the oestrous cycle has no effect on oxycodone intake and incubated oxycodone seeking in female rats under our experimental conditions. Furthermore, consistent with our previous findings in male rats, results here show that OFC also plays a critical role in incubated oxycodone seeking in female rats.


Subject(s)
Oxycodone , Prefrontal Cortex , Rats , Animals , Male , Female , Rats, Sprague-Dawley , Oxycodone/pharmacology , Self Administration , Drug-Seeking Behavior
4.
Clin Infect Dis ; 74(6): 1047-1054, 2022 03 23.
Article in English | MEDLINE | ID: mdl-34185838

ABSTRACT

BACKGROUND: Younger age of antiretroviral therapy (ART) initiation is associated with smaller viral reservoirs in perinatally acquired HIV-1 infection, but there is wide variability among early-treated infants. Predictors of this variability are not fully described. METHODS: Sixty-three neonates diagnosed with HIV-1 <48 hours after birth in Johannesburg, South Africa, were started on ART as soon as possible. Fifty-nine (94%) infants received nevirapine prophylaxis from birth until ART start. Viably preserved peripheral blood mononuclear cells (PBMCs) collected at regular intervals to 48 weeks, and from mothers at enrollment, were tested using integrase-targeted, semi-nested, real-time quantitative hydrolysis probe (TaqMan) PCR assays to quantify total HIV-1 subtype C viral DNA (vDNA). Predictors were investigated using generalized estimating equation regression. RESULTS: Thirty-one (49.2%) infants initiated ART <48 hours, 24 (38.1%) <14 days, and 8 (12.7%) >14 days of birth. Three-quarters were infected despite maternal antenatal ART (however, only 9.5% of women had undetectable viral load closest to delivery) and 86% were breastfed. Higher infant CD4+ T-cell percentage and viral load <100 000 copies/mL pre-ART were associated with lower vDNA in the first 48 weeks after ART start. No antenatal maternal ART and breastfeeding were also associated with lower vDNA. Older age at ART initiation had a discernible negative impact when initiated >14 days. CONCLUSIONS: Among very early treated infants, higher CD4+ T-cell percentage and viral load <100 000 copies/mL pre-ART, infection occurring in the absence of maternal antenatal ART, and breastfeeding were associated with lower levels of HIV-1 DNA in the first 48 weeks of treatment. Clinical Trials Registration. clinicaltrials.gov (NCT02431975).


Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Anti-HIV Agents/therapeutic use , DNA, Viral , Female , HIV Infections/prevention & control , HIV-1/genetics , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Leukocytes, Mononuclear , Pregnancy , South Africa/epidemiology , Viral Load
5.
Am J Perinatol ; 39(S 01): S42-S48, 2022 12.
Article in English | MEDLINE | ID: mdl-36307090

ABSTRACT

OBJECTIVE: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy has been associated with poor pregnancy outcomes. There is, however, not much information on the impact of the timing of SARS-CoV-2 infection on pregnancy outcomes, and studies from low-middle income settings are also scarce. STUDY DESIGN: We conducted a cross-sectional study from April to December 2020, in South Africa, to assess the association of SARS-CoV-2 infection on a nasal swab at the time of labor with fetal death, preterm birth, low birth weight, or pregnancy-induced complications. When possible, maternal blood, cord blood, and placenta were collected. SARS-CoV-2 infection was investigated by a nucleic acid amplification test (NAAT). RESULTS: Overall, 3,117 women were tested for SARS-CoV-2 on a nasal swab, including 1,562 (50%) healthy women with uncomplicated term delivery. A positive NAAT was detected among 132 (4%) women. Adverse birth outcomes or pregnancy-related complications were not associated with SARS-CoV-2 infection at the time of labor. Among SARS-CoV-2-infected women, an NAAT-positive result was also obtained from 6 out of 98 (6%) maternal blood samples, 8 out of 93 (9%) cord-blood samples, 14 out of 54 (26%) placentas, and 3 out of 22 (14%) nasopharyngeal swabs from newborns collected within 72 hours of birth. Histological assessment of placental tissue revealed that women with SARS-CoV-2 nasal infection had a higher odds (3.82, 95% confidence interval: 1.20, 12.19) of chronic chorioamnionitis compared with those without SARS-CoV-2 infection. CONCLUSION: Our study demonstrates that intrapartum, SARS-CoV-2 infection was not associated with evaluated poor outcomes. In utero fetal and placental infections and possible vertical and/or horizontal viral transfer to the newborn were detected among women with nasal SARS-CoV-2 infection. KEY POINTS: · Intrapartum SARS-CoV-2 infection was not associated with evaluated poor outcomes.. · In utero fetal and placental infections were detected among women with nasal SARS-CoV-2 infection.. · Women with SARS-CoV-2 nasal infection had a higher odds of chronic chorioamnionitis..


Subject(s)
COVID-19 , Chorioamnionitis , Pregnancy Complications, Infectious , Premature Birth , Infant, Newborn , Female , Pregnancy , Humans , Male , SARS-CoV-2 , Pregnancy Outcome , Chorioamnionitis/pathology , Cross-Sectional Studies , Placenta/pathology , Premature Birth/pathology , Infectious Disease Transmission, Vertical
6.
J Pediatr Gastroenterol Nutr ; 72(1): e15-e20, 2021 01 01.
Article in English | MEDLINE | ID: mdl-32804904

ABSTRACT

OBJECTIVES: Children with HIV (CHIV) have lifetime exposure to antiretrovirals (ART); therefore, optimizing their regimens to have the least impact on fat redistribution is a priority. METHODS: This is a cross-sectional study of 219 perinatally infected CHIV and 219 HIV-uninfected controls from similar socioeconomic backgrounds in Johannesburg, South Africa. We compared total body and regional fat distribution in CHIV on suppressive ART regimens with controls and, among CHIV, between ritonavir-boosted lopinavir (LPV/r)-based and efavirenz (EFV)-based regimens. RESULTS: The mean age of the 219 uninfected children (45% girls) and the 219 CHIV (48% girls) was 7.0 and 6.4 years, respectively. CHIV had lower adjusted total body fat (P = 0.005) and lower percentage fat at the trunk (P = 0.020), arms (P = 0.001), and legs (P < 0.001) than uninfected children. CHIV on LPV/r had similar body composition as those on EFV, except for arm fat mass (P = 0.030). When stratified by sex, girls with HIV on LPV/r had lower adjusted total (P = 0.007), trunk (P = 0.002), arms (P = 0.008), legs (P = 0.048) fat mass; trunk-to-total body fat (P = 0.044); and higher legs-to-total body fat (P = 0.011) than those on EFV. CONCLUSIONS: South African CHIV receiving ART had lower global and partial fat mass and percentage fat than healthy controls. In girls with HIV with sustained virologic suppression on ART, switching from LPV/r to EFV could attenuate fat mass loss, indicating that EFV-based regimen may be a better option in this group of individuals.


Subject(s)
Anti-HIV Agents , HIV Infections , Alkynes , Anti-HIV Agents/therapeutic use , Benzoxazines , Child , Cross-Sectional Studies , Cyclopropanes , Female , HIV Infections/drug therapy , Humans , Male , South Africa
7.
Child Care Health Dev ; 47(2): 154-162, 2021 03.
Article in English | MEDLINE | ID: mdl-33150965

ABSTRACT

BACKGROUND: Neurodevelopmental stimulation programmes can improve developmental outcomes. Antiretroviral therapy (ART) started soon after birth potentially limits the invasion of HIV into the central nervous system. A combination of developmental stimulation and early ART initiation may reduce developmental delays in children with perinatally acquired HIV infection. METHODS: At a single site in Johannesburg, South Africa, we enrolled 36 HIV-infected neonates on ART into an intervention group (IG) participating in a yearlong home-based, neurodevelopmental stimulation programme. Bayley Scales of Infant and Toddler Development-3rd Edition (BSID-III) assessments were conducted at 12 months. Scores were compared with 24 early treated HIV-infected infants in an observational group (OG). BSID-III assessments were also conducted for older children in an OG at 24 or 36 months. Cognitive, language and motor scaled and composite scores were analysed. RESULTS: BSID-III scaled and composite scores were all higher in the IG apart from the gross motor scaled score (9.25 vs. 10, p = 0.1954). Receptive communication scaled score was significantly higher in the IG (10.96 vs. 9, p = 0.0331). IG composite scores were all higher than OG scores. OG children assessed at 24 or 36 months had lower composite scores in all subscales than 12-month OG scores. CONCLUSIONS: Early treated HIV-infected children participating in a neurodevelopmental stimulation programme achieved higher BSID-III scores at 12 months compared with early treated HIV-infected children who did not receive the programme.


Subject(s)
HIV Infections , Adolescent , Child , Child Development , Cognition , HIV Infections/drug therapy , Humans , Infant , Infant, Newborn , South Africa/epidemiology
8.
J Pediatr ; 227: 308-313.e2, 2020 12.
Article in English | MEDLINE | ID: mdl-32712285

ABSTRACT

This study examined behavioral functioning and quality of life in South African children living with perinatally acquired HIV. Compared with controls, children living with perinatally acquired HIV had a higher mean total difficulties score assessed by the Strengths and Difficulties Questionnaire and lower mean quality of life scores assessed by the Pediatric Quality of Life Inventory.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/psychology , Problem Behavior , Quality of Life , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male , South Africa
9.
AIDS Care ; 32(11): 1421-1428, 2020 11.
Article in English | MEDLINE | ID: mdl-32122174

ABSTRACT

Introduction: Successful strategies preventing mother-to-child HIV transmission have resulted in increasing numbers of uninfected children exposed to maternal HIV and ART in-utero, and while breastfeeding. Some reports describe exposure as impacting neurodevelopment. Methods: This cross-sectional analysis included 49 of the 70 HIV-exposed uninfected (HEU) birth-enrolled children as the control arm of an observational cohort study of early treatment in HIV-infected infants in Johannesburg, South Africa. We used the Bayley Scales of Infant and Toddler Development-3rd Edition (BSID-III) to assess neurodevelopment at 12 months of age. Cognitive, language and motor subscale composite scores and performance categories were analysed. We evaluated associations between BSID-III performance categories and cohort variables. Results: Evaluating composite scores according to performance categories showed a higher percentage of scores in the average, high average and superior categories as compared to test reference norms. Maternal BMI ≥ 25 kg/m2 and mid-upper arm circumference ≥ 32 cm were associated with higher than average infant language scores. Six children scored below average (<90) - three in the cognitive and three in the language subscale. Conclusion: No developmental delay was found in ART-exposed HEU children at 12 months of age. A small number of at-risk children suggest ongoing screening, referral and follow-up is needed.


Subject(s)
Child Development , HIV Infections , Pregnancy Complications, Infectious , Breast Feeding , Case-Control Studies , Child Development/drug effects , Child, Preschool , Cohort Studies , Cross-Sectional Studies , Female , Humans , Infant , Infectious Disease Transmission, Vertical/prevention & control , Language Development , Neuropsychological Tests , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Prenatal Exposure Delayed Effects , Prospective Studies , South Africa/epidemiology
10.
AIDS Care ; 32(4): 438-444, 2020 04.
Article in English | MEDLINE | ID: mdl-31288549

ABSTRACT

Little is known about how growing up with HIV impacts educational outcomes in sub-Saharan African children. We evaluated if South African children living with HIV (CLWH) were in the appropriate school grade-for-age compared to uninfected control children. We observed higher rates of not being in the correct grade-for-age in CLWH compared with controls (OR 3.32, 95% CI: 2.07-5.34), adjusted for study site, sex, whether the child's biological father was alive, and caregiver education. Initiation of ART before 6 months of age reduced but did not eliminate this association. Whether these associations are due to biological factors or other social and environmental determinants, and how best to support CLWH to achieve educational goals, warrants further investigation.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Educational Status , HIV Infections/drug therapy , Case-Control Studies , Child , Disease Transmission, Infectious , Education , Female , HIV Infections/complications , HIV Infections/epidemiology , Humans , Male , South Africa/epidemiology
11.
Curr Pain Headache Rep ; 24(8): 41, 2020 Jun 11.
Article in English | MEDLINE | ID: mdl-32529416

ABSTRACT

PURPOSE OF REVIEW: Postmastectomy pain syndrome (PMPS) remains poorly defined, although it is applied to chronic neuropathic pain following surgical procedures of the breast, including mastectomy and lumpectomy in breast-conserving surgery. It is characterized by persistent pain affecting the anterior thorax, axilla, and/or medial upper arm following mastectomy or lumpectomy. Though the onset of pain is most likely to occur after surgery, there may also be a new onset of symptoms following adjuvant therapy, including chemotherapy or radiation therapy. RECENT FINDINGS: The underlying pathophysiology is likely multifactorial, although exact mechanisms have yet to be elucidated. In this regard, neuralgia of the intercostobrachial nerve is currently implicated as the most common cause of PMPS. Numerous pharmacological options are available in the treatment of PMPS, including gabapentinoids, tricyclic antidepressants, selective serotonin reuptake inhibitors, NMDA receptor antagonists, and nefopam (a non-opioid, non-steroidal benzoxazocine analgesic). Minimally invasive interventional treatment including injection therapy, regional anesthesia, botulinum toxin, and neuromodulation has been demonstrated to have some beneficial effect. A comprehensive update highlighting current perspectives on the treatment of postmastectomy pain syndrome is presented with emphasis on treatments currently available and newer therapeutics currently being evaluated to alleviate this complex and multifactorial condition.


Subject(s)
Mastectomy , Neuralgia/therapy , Pain, Postoperative/therapy , Acetylcholine Release Inhibitors/therapeutic use , Analgesics/therapeutic use , Anesthesia, Conduction , Anesthetics, Local/therapeutic use , Antidepressive Agents, Tricyclic/therapeutic use , Arm , Axilla , Botulinum Toxins, Type A/therapeutic use , Electric Stimulation Therapy/methods , Gabapentin/therapeutic use , Ganglia, Spinal , Humans , Memantine/therapeutic use , Nefopam/therapeutic use , Nerve Block , Neuralgia/diagnosis , Neuralgia/epidemiology , Pain Management , Pain, Postoperative/diagnosis , Pain, Postoperative/epidemiology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Selective Serotonin Reuptake Inhibitors/therapeutic use , Thoracic Wall , Trigger Points
12.
Paediatr Child Health ; 25(2): 79-81, 2020 Mar.
Article in English | MEDLINE | ID: mdl-33390743

ABSTRACT

The prevalence of food allergy in North America is high, and has increased over time. As a result, focus has shifted from treatment to allergy prevention. Previous studies have suggested that hydrolyzed formula may prevent atopic dermatitis in high-risk infants. As a result, multiple international guidelines including the Canadian Paediatric Society (CPS) position statement on allergy prevention recommend the use of hydrolyzed formula as a means of allergy prevention in mothers who are not breastfeeding or using donor breastmilk. However, a recent systematic review has not supported an association between use of hydrolyzed formula and allergy prevention. In addition, studies are emerging supporting the use of early and regular cow's milk formula as a means of cow's milk allergy prevention.

13.
J Pediatr ; 215: 267-271.e2, 2019 12.
Article in English | MEDLINE | ID: mdl-31474425

ABSTRACT

We evaluated bone quality among South African children with HIV over a 2-year period by quantitative ultrasound (QUS). Children with HIV have persistently lower bone quality compared with controls reflecting increased porosity, reduced strength, and possibly an increased short- and long-term risk of fracture.


Subject(s)
Bone Density/physiology , Calcaneus/diagnostic imaging , HIV Infections/physiopathology , Anti-Retroviral Agents/therapeutic use , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Female , HIV Infections/drug therapy , Humans , Longitudinal Studies , Male , South Africa/epidemiology , Ultrasonography
14.
J Gerontol Nurs ; 45(7): 36-45, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31237660

ABSTRACT

The current study focuses on the short-term effect of MARIO, a social robot, on quality of life, depression, and perceived social support in persons with dementia (PWD) and evaluates their acceptability of MARIO. Ten PWD in one nursing home took part in a 4-week pilot study, where each participant had up to 12 sessions with MARIO. Sessions comprised engagement in music, news, reminiscence, games, and calendar applications. Standardized questionnaires were administered before and after the 4-week period. Participants had a sustained interest in MARIO during their interactions and an acceptance of MARIO's appearance, sound, and applications. Consequently, participants spent more time socially engaged. No statistically significant differences were found in quality of life, depression, and perceived social support. PWD can engage with a social robot in a real-world nursing home. Future research should incorporate a larger sample and longer intervention period. [Journal of Gerontological Nursing, 45(7), 36-45.].


Subject(s)
Dementia/nursing , Residential Facilities , Robotics , Aged , Dementia/psychology , Female , Humans , Ireland , Male , Qualitative Research
15.
Vet Clin North Am Equine Pract ; 34(1): 81-96, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29402479

ABSTRACT

Differentiating between medical and surgical causes of colic is one of the primary goals of the colic workup, because early surgical intervention improves prognosis in horses requiring surgery. Despite the increasing availability of advanced diagnostics (hematologic analyses, abdominal ultrasound imaging, etc), the most accurate indicators of the need for surgery remain the presence of moderate to severe signs of abdominal pain, recurrence of pain after appropriate analgesic therapy, and the absence of intestinal borborygmi. Investigation of novel biomarkers, which may help to differentiate surgical lesions from those that can be managed medically, continues to be an active area of research.


Subject(s)
Colic/veterinary , Horse Diseases/diagnosis , Horse Diseases/therapy , Postoperative Complications/veterinary , Acute Disease , Animals , Colic/diagnosis , Colic/surgery , Colic/therapy , Horse Diseases/surgery , Horses , Ileus , Postoperative Complications/etiology
16.
Curr Atheroscler Rep ; 19(12): 60, 2017 Nov 07.
Article in English | MEDLINE | ID: mdl-29116404

ABSTRACT

PURPOSE OF REVIEW: Populations with significant dietary fish intake tend to have lower cardiovascular (CV) risk and demonstrable physiologic differences including lower lipid/lipoprotein levels and other direct and indirect effects on the arterial wall and inhibiting factors that promote atherosclerosis. Treatment with high doses of pharmacologic-grade omega-3 fatty acid (n-3FA) supplements achieves significant reductions in triglycerides (TG), non-high-density lipoprotein- (non-HDL-) and TG-rich lipoprotein- (TRL-) cholesterol levels. n-3FA supplements have significant effects on markers of atherosclerosis risk including endothelial function, low-density lipoprotein (LDL) oxidation, cellular and humoral markers of inflammation, hemodynamic factors, and plaque stabilization. This review summarizes the lipid and cardiometabolic effects of prescription-grade n-3FAs and will discuss clinical trials, national/organizational guidelines, and expert opinion on the impact of supplemental n-3FAs on CV health and disease. RECENT FINDINGS: Clinical trial evidence supports use of n-3FAs in individuals with established atherosclerotic cardiovascular disease (ASCVD), but the data either does not support or is lacking for other types of cardiometabolic risk including prevention of stroke, treatment in patients with heart failure, diabetes mellitus and prediabetes, and for primary prevention in the general population. Despite inconsistent findings to support widespread benefit, there is persistent population-wide enthusiasm for n-3FA as a dietary supplement for its cardiometabolic benefits. Fortunately, there are ongoing clinical trials to assess whether the lipid/lipoprotein benefits may be extended to other at-risk populations and whether lower-dose therapy may provide background benefit for primary prevention of ASCVD.


Subject(s)
Cardiovascular Diseases/drug therapy , Fatty Acids, Omega-3/therapeutic use , Metabolic Diseases/drug therapy , Dietary Supplements , Humans
17.
Vet Surg ; 45(2): 201-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26767324

ABSTRACT

OBJECTIVE: To report surgical complications, occurrence of post-obliteration colic, long term outcome, and return to previous function for horses treated with prosthetic mesh obliteration of the nephrosplenic space. STUDY DESIGN: Retrospective study. ANIMALS: Horses (n = 26) having nephrosplenic space obliteration using prosthetic mesh. METHODS: Horses undergoing mesh obliteration between January 2006 and May 2013 were included. A Proxplast™ mesh was secured to the nephrosplenic space with titanium helical coils in standing horses using laparoscopic technique. Perioperative data were obtained from the medical record and by telephone followup. Tests of proportion were used to compare the study population to the hospital colic population. Occurrence of colic within 1 year of obliteration was compared between horses where the diagnosis was confirmed at laparotomy and those diagnosed by abdominal palpation per rectum using a Fisher's exact test. RESULTS: All 26 horses undergoing mesh obliteration during the study period survived to discharge. Long term followup was available for 25 horses, with 23 returning to their previous level of function, and 21 alive at the time of followup. Cause of death was not associated with the surgical procedure in any case. Geldings and Warmbloods were overrepresented compared to the hospital colic population. Ten horses (38%) demonstrated colic after mesh obliteration. All 10 horses were examined by a veterinarian and none were diagnosed with recurrence of nephrosplenic entrapment. CONCLUSION: Mesh obliteration of the nephrosplenic space is an effective alternative to suture closure for preventing nephrosplenic entrapment of the large colon in horses. No complications related to mesh obliteration were reported in our study population.


Subject(s)
Colic/veterinary , Colonic Pseudo-Obstruction/veterinary , Horse Diseases/surgery , Surgical Mesh/veterinary , Animals , Colic/surgery , Colonic Pseudo-Obstruction/surgery , Female , Horses , Laparoscopy/veterinary , Laparotomy/veterinary , Male , Posture , Recurrence , Retrospective Studies , Treatment Outcome
18.
N Engl J Med ; 364(2): 127-35, 2011 Jan 13.
Article in English | MEDLINE | ID: mdl-21226578

ABSTRACT

BACKGROUND: High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden. METHODS: We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima-media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B-depleted serum from the study participants. RESULTS: The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima-media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P=0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P=0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins. CONCLUSIONS: Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.).


Subject(s)
Cholesterol/metabolism , Coronary Artery Disease/metabolism , Foam Cells/metabolism , Lipoproteins, HDL/metabolism , Aged , Biological Transport/drug effects , Carotid Arteries/anatomy & histology , Carotid Arteries/pathology , Case-Control Studies , Coronary Artery Disease/diagnostic imaging , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Lipoproteins, HDL/blood , Logistic Models , Middle Aged , Pioglitazone , Radiography , Smoking , Thiazolidinediones/pharmacology
19.
Am J Vet Res ; 85(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38484466

ABSTRACT

OBJECTIVE: Plasma cytokine adsorption has shown benefit as an adjunctive therapy in human sepsis but has yet to be investigated in horses. We hypothesized that ex vivo filtration of equine plasma with a novel cytokine adsorption device would significantly reduce concentrations of lipopolysaccharide-stimulated cytokines. We also hypothesized that the device would adsorb medications commonly used to treat sepsis. ANIMALS: 8 horses owned by North Carolina State University. METHODS: Four liters of heparinized whole blood was collected from healthy adult horses (n = 8) and stimulated with lipopolysaccharide (100 ng/mL) for 6 hours (37 °C.) from June 4, 2023, to December 15, 2023. Plasma was filtered through a cytokine adsorption device or sham circuit. Samples were collected at 11 time points for multiplex cytokine analysis. Chemistry analysis was performed before and after filtration. To investigate the impact of the device on medication concentrations, equine plasma containing potassium penicillin, gentamicin, and flunixin meglumine was filtered through the cytokine adsorption device or sham for 6 hours. Drug concentrations before and after filtration were determined by ultra-high-performance liquid chromatography. Prefiltration versus postfiltration sample concentrations were analyzed by Student paired t test using GraphPad Prism 9.0 (P < .05). RESULTS: Filtration of lipopolysaccharide-stimulated equine plasma (n = 8) for 6 hours resulted in significant mean reductions in the cytokines IL-10, IL-5, IL-8, tumor necrosis factor-α (TNF-α), and IL-1ß, as well as albumin. Drug concentrations of potassium penicillin, gentamicin, and flunixin meglumine were also significantly reduced by filtration. CLINICAL RELEVANCE: This work provides proof of concept for further investigation of extracorporeal cytokine adsorption as a potential adjunct treatment for equine sepsis.


Subject(s)
Cytokines , Lipopolysaccharides , Animals , Horses , Cytokines/metabolism , Cytokines/blood , Horse Diseases/therapy , Sepsis/veterinary , Sepsis/therapy , Adsorption , Male , Female , Anti-Bacterial Agents
20.
Front Vet Sci ; 11: 1414426, 2024.
Article in English | MEDLINE | ID: mdl-38803798

ABSTRACT

Objective: Develop, implement, and monitor for adverse effects of, a novel hemoperfusion therapy in adult horses. Methods: A prospective, observational feasibility study using three healthy adult horses from the North Carolina State University teaching herd. Health status was determined by physical exam, complete blood count, coagulation panel, and serum biochemistry. Each horse was instrumented with a 14 Fr × 25 cm double-lumen temporary hemodialysis catheter and underwent a 240 min polymer-based hemoperfusion session. Horses were administered unfractionated heparin to maintain anti-coagulation during the session. Given the novelty of this therapy in horses, each horse was treated as a learning opportunity that informed an iterative process of protocol development and modification. Measurements and main results: Our long-term goal is to investigate potential clinical applications of hemoperfusion in horses, including cytokine reduction in horses with severe SIRS/sepsis. Horses were monitored for changes in clinical exam, biochemistry and hematology parameters. Additionally, cytokines were quantified to determine whether extracorporeal hemadsorption therapy alone caused an inflammatory response. Our results show that hemoperfusion therapy was associated with decreased platelet counts and serum albumin concentration. There was no significant change in plasma cytokine concentrations with hemoperfusion therapy. In one horse, the cytokine concentrations decreased, as previously reported with hemoperfusion therapy in humans. Hypothesis: We hypothesized that hemoperfusion therapy could be performed in healthy adult horses without significant adverse effects. Conclusion: Polymer-based hemoperfusion is a feasible extracorporeal therapy (ECT) modality for adult horses. Additional studies are needed to further establish clinical protocols, as well as establish efficacy of polymer-based hemoperfusion for treatment of various conditions in horses, including intoxications, immune-mediated conditions, and sepsis.

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