Comparison of Breastfeeding Practices in Mothers With Chronic Kidney Disease With or Without Kidney Transplantation.

Introduction: Existing literature on pregnant patients with chronic kidney disease (CKD) with or without kidney transplantation focuses mainly on their pregnancy outcomes, but there are scant data on their lactation outcomes. Our objective was to characterize the lactation outcomes of patients with CKD with or without kidney transplantation. Methods: This is a single-institution retrospective cohort study of female-identifying patients with CKD with or without kidney transplantation who had a birth hospitalization at a tertiary health system between 2010 and 2020. Maternal and pediatric data on medical history, pregnancy, delivery, neonatal, and lactation outcomes, medications, and care team involved were collected. Primary outcome measures were breastfeeding initiation within 24-hour postpartum, breastfeeding 8 or more times per day during hospitalization, and any breastfeeding beyond 1 month. Health professionals' comments related to lactation and medications were extracted for qualitative data analysis. Results: Patients with and without kidney transplantation had similar comorbidities, pregnancy, delivery, and neonatal outcomes, and hospital length of stay (p > 0.05). Patients without kidney transplantation were more likely to initiate breastfeeding in the first 24 hours (p = 0.03) after delivery and continue breastfeeding beyond 1 month postpartum. There was a lack of consistency between specialties regarding medication compatibility with lactation. Patients on immunosuppression were more likely to exclusively formula feed (p = 0.02) or to initiate breastfeeding and then switch to formula (p = 0.0004) because of their immunosuppressive medications versus patients on any other medication. Conclusion: Patients with CKD but without a kidney transplantation were more likely to initiate breastfeeding or provide breast milk to their infant within 24 hours of delivery, breastfeed >8 times per day during their hospital stay, and breastfeed beyond a month postpartum than those with a transplanted kidney. Lactation support and pharmacology should be incorporated into graduate medical education.

Randomised clinical non-inferiority trial of breathing-based meditation and cognitive processing therapy for symptoms of post-traumatic stress disorder in military veterans.

OBJECTIVE: Test whether Sudarshan Kriya Yoga (SKY) was non-inferior to cognitive processing therapy (CPT) for treating symptoms of post-traumatic stress disorder (PTSD) among veterans via a parallel randomised controlled non-inferiority trial. SETTING: Outpatient Veterans Affairs healthcare centre. PARTICIPANTS: 85 veterans (75 men, 61% white, mean age 56.9) with symptoms of PTSD participated between October 2015 and March 2020: 59 participants completed the study. INTERVENTIONS: SKY emphasises breathing routines and was delivered in group format in a 15-hour workshop followed by two 1-hour sessions per week for 5 weeks. CPT is an individual psychotherapy which emphasises shifting cognitive appraisals and was delivered in two 1-hour sessions per week for 6 weeks. MEASURES: The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). The secondary measures were the Beck Depression Inventory-II (BDI-II) and Positive and Negative Affect Scale (PANAS). RESULTS: Mean PCL-C at baseline was 56.5 (±12.6). Intent-to-treat analyses showed that PCL-C scores were reduced at 6 weeks (end of treatment) relative to baseline (SKY, -5.6, d=0.41, n=41: CPT, -6.8, d=0.58, n=44). The between-treatment difference in change scores was within the non-inferiority margin of 10 points (-1.2, 95% CI -5.7 to 3.3), suggesting SKY was not inferior to CPT. SKY was also non-inferior at 1-month (CPT-SKY: -2.1, 95% CI -6.9 to 2.8) and 1-year (CPT-SKY: -1.8, 95% CI -6.6 to 2.9) assessments. SKY was also non-inferior to CPT on the BDI-II and PANAS at end of treatment and 1 month, but SKY was inferior to CPT on both BDI-II and PANAS at 1 year. Dropout rates were similar (SKY, 27%, CPT, 34%: OR=1.36, 95% CI 0.51 to 3.62, p=0.54). CONCLUSIONS: SKY may be non-inferior to CPT for treating symptoms of PTSD and merits further consideration as a treatment for PTSD. TRIAL REGISTRATION NUMBER: NCT02366403.

Yoga is effective in treating symptoms of Gulf War illness: A randomized clinical trial.

Many Veterans of the 1990-1991 Gulf War report symptoms of Gulf War Illness, a condition involving numerous chronic symptoms including pain, fatigue, and mood/cognition symptoms. Little is known about this condition's etiology and treatment. This study reports outcomes from a randomized controlled single-blind trial comparing yoga to cognitive behavioral therapy for chronic pain and other symptoms of Gulf War Illness. Participants were Veterans with symptoms of GWI: chronic pain, fatigue and cognition-mood symptoms. Seventy-five Veterans were randomized to treatment via selection of envelopes from a bag (39 yoga, 36 cognitive behavioral therapy), which consisted of ten weekly group sessions. The primary outcomes of pain severity and interference (Brief Pain Inventory- Short Form) improved in the yoga condition (Cohen's d = .35, p = 0.002 and d = 0.69, p < 0.001, respectively) but not in the CBT condition (d = 0.10, p = 0.59 and d = 0.25 p = 0.23). However, the differences between groups were not statistically significant (d = 0.25, p = 0.25; d = 0.43, p = 0.076), though the difference in an a-priori-defined experimental outcome variable which combines these two variables into a total pain variable (d = 0.47, p = 0.047) was significant. Fatigue, as indicated by a measure of functional exercise capacity (6-min walk test) was reduced significantly more in the yoga group than in the CBT group (between-group d = .27, p = 0.044). Other secondary outcomes of depression, wellbeing, and self-reported autonomic nervous system symptoms did not differ between groups. No adverse events due to treatment were reported. Yoga may be an effective treatment for core Gulf War Illness symptoms of pain and fatigue, making it one of few treatments with empirical support for GWI. Results support further evaluation of yoga for treating veterans with Gulf War Illness. CLINICAL TRIAL REGISTRY: clinicaltrials.gov Registration Number NCT02378025.

Global connectivity and local excitability changes underlie antidepressant effects of repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is a commonly- used treatment for major depressive disorder (MDD). However, our understanding of the mechanism by which TMS exerts its antidepressant effect is minimal. Furthermore, we lack brain signals that can be used to predict and track clinical outcome. Such signals would allow for treatment stratification and optimization. Here, we performed a randomized, sham-controlled clinical trial and measured electrophysiological, neuroimaging, and clinical changes before and after rTMS. Patients (N = 36) were randomized to receive either active or sham rTMS to the left dorsolateral prefrontal cortex (dlPFC) for 20 consecutive weekdays. To capture the rTMS-driven changes in connectivity and causal excitability, resting fMRI and TMS/EEG were performed before and after the treatment. Baseline causal connectivity differences between depressed patients and healthy controls were also evaluated with concurrent TMS/fMRI. We found that active, but not sham rTMS elicited (1) an increase in dlPFC global connectivity, (2) induction of negative dlPFC-amygdala connectivity, and (3) local and distributed changes in TMS/EEG potentials. Global connectivity changes predicted clinical outcome, while both global connectivity and TMS/EEG changes tracked clinical outcome. In patients but not healthy participants, we observed a perturbed inhibitory effect of the dlPFC on the amygdala. Taken together, rTMS induced lasting connectivity and excitability changes from the site of stimulation, such that after active treatment, the dlPFC appeared better able to engage in top-down control of the amygdala. These measures of network functioning both predicted and tracked clinical outcome, potentially opening the door to treatment optimization.

Cardiovascular issues of COX-2 inhibitors and NSAIDs.

BACKGROUND: Rofecoxib (Vioxx) was withdrawn from the market because of increased death from cardiovascular (CV) events. Other selective cyclooxygenase-2 (COX-2) inhibitors and traditional nonsteroidal anti-inflammatory drugs (NSAIDs) may share this risk, but to what extent is unclear. OBJECTIVE: This article reviews the available evidence using a PubMed search for increased CV risk with COX-2 inhibitors and NSAIDs, explores possible mechanisms, and makes recommendations for their appropriate use in clinical practice. DISCUSSION: Rofecoxib, celecoxib, and the combination of valdecoxib and parecoxib have been found in prospective trials to increase CV risk. NSAIDs have also been found to be associated with increased CV risk in observational studies, but large randomised controlled trials with adequate follow up are required to further investigate this. Recommendations are to use drugs at lowest dose and for shortest duration possible. In patients with or at high risk for CV disease, COX-2 inhibitors are contraindicated. A traditional NSAID plus proton pump inhibitor may be used, but with caution.

The effect of joint aspiration and corticosteroid injections in osteoarthritis of the knee.

AIM: To evaluate the benefits of knee joint aspiration and injection in knee osteoarthritis (OA). METHODS: A retrospective, pilot study involved 110 patients with knee OA from a dedicated OA clinic in a Melbourne tertiary hospital from 2007 to 2009. Only those who had completed two Multiple Attribute Prioritization Tool (MAPT) questionnaires within 6 months of the initial review were included. The MAPT was designed to help prioritise patients on orthopedic waiting lists. Three groups were analyzed: patients who had no corticosteroid injection or aspiration, patients who received corticosteroid injections, and patients who received both joint aspiration with corticosteroid injections. RESULTS: Patients who had both joint aspiration and injection reported an improvement in pain compared with those who had no injection (56.3%vs. 32.2%, P = 0.03). Those who had joint injections also did better than those without injection (62.7%vs. 32.2%, P = 0.001). Reduced analgesia use was noted in 12.5% of patients with aspiration and injection compared with 1.7% with no injection or aspiration (P = 0.03). Improved walking distance was noted in 22.4% of patients who had injections compared with 8.5% of patients with no injections (P = 0.03). No significant differences in MAPT scores among the different treatment groups were noted. CONCLUSION: This pilot study appears to show a beneficial trend in giving corticosteroid injections and to aspirate the knee in OA patients. Further studies are needed to address the mechanical benefits, quadriceps strengthening and pain reduction with knee aspiration, as well as the effects that different volumes of fluid may have on knee mechanics and symptoms.

Paradoxical association of C-reactive protein with endothelial function in rheumatoid arthritis.

BACKGROUND: Within the general population, levels of C-reactive protein (CRP) are positively associated with atherosclerotic cardiovascular disease (CVD). Whether CRP is causally implicated in atherogenesis or is the results of atherosclerosis is disputed. A role of CRP to protect endothelium-derived nitric oxide (EDNO) has been suggested. We examined the association of CRP with EDNO-dependent vasomotor function and subclinical measures of atherosclerosis and arteriosclerosis in patients with raised CRP resulting from rheumatoid arthritis (RA). METHODOLOGY/PRINCIPAL FINDINGS: Patients with RA (n = 59) and healthy control subjects (n = 123), underwent measures of high sensitivity CRP, flow-mediated dilation (FMD, dependent on EDNO), intima-media thickness (IMT, a measure of subclinical atherosclerosis) and aortic pulse wave velocity (PWV, a measure of arteriosclerosis). IMT and PWV were elevated in patients with RA compared to controls but FMD was similar in the two groups. In patients with RA, IMT and PWV were not correlated with CRP but FMD was positively independently correlated with CRP (P<0.01). CONCLUSIONS/SIGNIFICANCE: These findings argue against a causal role of CRP in atherogenesis and are consistent with a protective effect of CRP on EDNO bioavailability.

Thioflavin T fluorescence in human serum: correlations with vascular health and cardiovascular risk factors.

OBJECTIVES: Amyloid fibrils and amyloid-like structures are implicated in atherosclerosis via macrophage activation and inflammation. A common property of amyloid-like structures is their ability to induce thioflavin T (ThT) fluorescence. We measured ThT fluorescence in serum and related these levels to traditional cardiovascular risk factors and non-invasive measures of vascular dysfunction (elasticity). In addition, chemically modified serum components that contribute to serum ThT fluorescence were explored and identified. DESIGN, METHODS, AND RESULTS: Sera from 105 people, including 35 healthy subjects, and 70 high cardiovascular risk patients (36 with rheumatoid arthritis and 34 with systemic lupus erythrematosus) showed an 8.75-fold variation in induced ThT fluorescence. Although mean (+/-SD) ThT fluorescence did not differ significantly between groups (controls 0.97+/-0.26, RA 1.12+/-0.45, and SLE 0.74+/-0.23), the combined data set showed significant inverse correlation (p=0.046) between ThT fluorescence tertiles and small artery elasticity. Correlation was also found between ThT fluorescence tertiles and LDL-cholesterol, total-cholesterol, and C-reactive protein. Floatation fractionation of apoB containing lipoproteins showed that ThT reactivity in this fraction correlated with both serum oxidised-LDL and LDL-cholesterol levels. However, approximately 94% of ThT reactivity in serum was associated with the non-apoB containing serum fraction, with the majority of ThT fluorescence associated with albumin. Incubation of purified albumin with glucose or with methylglyoxal induced ThT fluorescence, suggesting that glycated or chemical adducts of albumin contribute to the variation in ThT fluorescence of human serum. CONCLUSIONS: We propose that the detection of these adducts in serum using ThT fluorescence measurements may provide a marker for chemically modified protein structures that could assist the assessment of cardiovascular disease risk.

Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased rates of cardiovascular disease. Reduced small artery elasticity (SAE) and large artery elasticity (LAE) and increased systemic vascular resistance (SVR) have been found in other high-risk groups. In the present study, we sought to determine whether arterial elasticity was reduced and SVR was increased in RA patients compared with controls matched for coronary artery disease (CAD) status, and to relate the results to vascular disease risk factors, including measures of inflammation. METHODS: Arterial elasticity was assessed by pulse wave analysis in RA patients with (n = 15) and without (n = 38) CAD, and in controls matched 1:1 for age, sex, and CAD status. Vascular risk factors, including high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1 (sVCAM-1), and serum amyloid A (SAA) levels, were assessed. RESULTS: SAE and LAE were significantly lower and SVR was significantly higher in RA patients than in controls. RA patients also had higher levels of hsCRP, SAA, and sVCAM-1. SAE and LAE values were inversely correlated with markers of inflammation. Associations of SAE and LAE with RA were independent of conventional risk factors, but were dependent on markers of inflammation. CONCLUSION: Vascular function is abnormal in RA, with reduced SAE and LAE and increased SVR relative to controls. Arterial elasticity is inversely associated with measures of inflammation. These measures may be clinically useful in the detection and monitoring of vascular disease in RA.