Preventing persistent postsurgical pain: A systematic review and component network meta-analysis.

BACKGROUND AND OBJECTIVES: Evidence for perioperative methods to prevent persistent postsurgical pain (PPP) is uncertain, in part because few treatments have been directly compared. Here we have used component network meta-analysis (cNMA) to incorporate both direct and indirect evidence in the evaluation of the efficacy and tolerability of pharmacological and neural block treatments. DATABASES AND DATA TREATMENT: We searched the Cochrane Central Registry of Controlled Trials, Embase, MEDLINE, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry up to January 2021 for randomized, double-masked, controlled trials that reported the prevalence of PPP. We assessed trial quality with the Cochrane risk of bias tool (RoB 2.0). We analysed the results with frequentist cNMA models. The primary outcome was the relative risk (RR) of PPP. We assessed efficacy in relation to a clinically important effect size of RR = 0.9, which is a 10% improvement with treatment. RESULTS: The analysis included 107 trials (13,553 participants) of 13 treatments. The effects of complex interventions were the multiplicative effects of their components. Compared with placebo, serotonin-norepinephrine reuptake inhibitors (SNRIs), neural block alone, or in combination with NMDA receptor blockers or gabapentanoids were effective. Treatments with benefit in the immediate post-operative period predicted a reduced risk of PPP. CONCLUSIONS: Several treatments and treatment combinations effectively reduce PPP prevalence. Pain outcomes in the immediate postoperative period are an important mediator of PPP. Multimodal interventions can be analysed using cNMA. SIGNIFICANCE: Systematic reviews of PPP prevention usually focus on the efficacy of specific treatments in comparison with control interventions. In this study we used component network meta-analysis to compare interventions to each other, including both pharmacological and neural block techniques, and multimodal interventions. Interventions that are not effective alone may improve the efficacy of multimodal interventions that include neural block techniques. Immediate postoperative benefit was an important mediator for reduction of PPP. STUDY REGISTRATION: PROSPERO: CRD42018085570 https://www.crd.york.ac.uk/prospero/.

Epidemiological study of Coxiella burnetii in dairy cattle and small ruminants in Québec, Canada.

The bacterium Coxiella burnetii (C. burnetii) can infect a wide range of animals, most notably ruminants where it causes mainly asymptomatic infections and, when clinical, it is associated with reproductive disorders such as abortion. It is also the etiological agent of Q fever in humans, a zoonosis of increasingly important public health concern. A cross-sectional study was performed to estimate the apparent prevalence and spatial distribution of C. burnetii positivity in dairy cattle and small ruminant herds of two regions of Québec, Canada, and identify potential risk factors associated with positivity at animal and herd levels. In dairy cattle herds, individual fecal samples and repeated bulk tank milk samples (BTM) were collected. In small ruminant herds, serum and feces were sampled in individual animals. ELISA analyses were performed on serum and BTM samples. Real-time quantitative PCR (qPCR) was done on fecal and BTM samples. An animal was considered C. burnetii-positive when at least one sample was revealed positive by ELISA and/or qPCR, while a herd was considered C. burnetii-positive when at least one animal inside that herd was revealed positive. None of the 155 cows had a qPCR-positive fecal sample, whereas 37.2 % (95 % CI = 25.3-49.1) of the 341 sheep and 49.2 % (95 % CI = 25.6-72.7) of the 75 goats were C. burnetii-positive. The apparent prevalence of C. burnetii-positive herds was 47.3 % (95 % CI = 35.6-59.3) in dairy cattle herds (n = 74), 69.6 % (95 % CI = 47.1-86.8) in sheep flocks (n = 23) and 66.7 % (95 % CI = 22.3-95.7) in goat herds (n = 6). No spatial cluster of positive herds was detected. At the individual level, the only significant association with positivity in multivariable regressions was higher parity number in small ruminants. At the herd level, the use of calving group pen, the distance to the closest positive bovine herd, and small ruminant herd density in a 5 km radius were associated with dairy cattle herd positivity, whereas small ruminant herds with more than 100 animals and with a dog on the farm had greater odds of C. burnetii positivity. Our study shows that the infection is frequent on dairy cattle and small ruminant herds from the two studied regions and that some farm and animal characteristics might influence the transmission dynamics of the C. burnetii infection.

Prevalence of shedding and antibody to Coxiella burnetii in post-partum dairy cows and its association with reproductive tract diseases and performance: A pilot study.

The bacterium Coxiella burnetii has been associated with reproduction disorders in dairy cattle. A cross-sectional study was conducted in Québec, Canada, to estimate the prevalence of C. burnetii in dairy cows from C. burnetii RT-PCR-positive and/or ELISA-positive herds. As a secondary objective, the associations between C. burnetii-positivity and three reproductive outcomes (purulent vaginal discharge, cytological endometritis, and success at first service) were assessed. A total of 202 post-parturient dairy cows from nine herds were sampled at 35 ± 7 days in milk. Vaginal mucus and composite milk were collected from each cow and screened for the presence of C. burnetii by real-time PCR (RT-PCR) and ELISA, respectively. Purulent vaginal discharge and cytological endometritis were evaluated using a Metricheck device and a modified cytobrush, respectively. The first insemination postpartum was done following an ovulation synchronization protocol around 70 days in milk, and success at first service was recorded. Multilevel logistic regressions adjusted for parity were used to model purulent vaginal discharge, cytological endometritis and success at first service according to C. burnetii cow status. All 202 RT-PCR-assayed vaginal samples were C. burnetii-negative. A positive result for anti-C. burnetii antibodies detection in composite milk was obtained in 25/202 samples and a doubtful result in 4/202 samples. After adjustment for sampling weights, the 202 ELISA-assayed composite milk samples gave an estimated overall prevalence of C. burnetii positive cows of 12.9 % (CI = 6.1-19.6 %) and of doubtful cows of 1.4 % (CI = 0.0-3.3 %). The proportion of ELISA-positive cows was lower in first parity (0%) compared to second (17.1 %) or third parity cows (20.0 %). The associations between ELISA positivity and reproductive outcomes were not statistically significant, perhaps due to the limited sample size, but could be used as pilot estimate for large-scale studies investigating the impact of C. burnetii infection on reproduction disorders in dairy cattle.

Harm Reduction Coverage and Hepatitis C Incidence: Findings From a Cohort of People Who Inject Drugs.

INTRODUCTION: Needle and syringe programs and opioid agonist therapy are essential for harm reduction among people who inject drugs. Few studies assess their combined potential in preventing hepatitis C virus infection. No studies have assessed whether they perform similarly among individuals at risk of primary and recurrent infection. This study aimed to estimate the rates of hepatitis C virus acquisition according to harm reduction coverage among hepatitis C virus-naive and previously infected people who inject drugs in Montreal, Canada. METHODS: This prospective cohort study involved regular interviews and hepatitis C antibody and RNA testing (data collection: 2010-2017, analysis: 2018). Opioid agonist therapy coverage was defined by current dose: high (≥60 mg/day methadone, ≥16 mg buprenorphine), low, or none. Complete needle and syringe program coverage was defined as exclusively reporting safe needle and syringe sources (past 6 or 3 months). Combined coverage was defined as full (high-dose agonist/complete needle/syringe coverage), minimal (low-dose agonist/incomplete needle/syringe coverage), and partial (remaining combinations). Cox regression models were fit. RESULTS: A total of 106 events were observed over 1,183.1 person-years for primary and recurrent incidence rates of 10.6 (95% CI=8.0, 13.8) and 7.6 (95% CI=5.6, 9.9) per 100 years, respectively. High-dose opioid agonist therapy was associated with a 77% reduction in hepatitis C virus acquisition (hazard ratio=0.23, 95% CI=0.10, 0.50) compared with not receiving opioid agonist therapy. Needle and syringe coverage was not associated with infection rates. Estimates considering their combination reflected opioid agonist therapy coverage. Associations were similar among hepatitis C virus-naive and previously infected people who inject drugs. CONCLUSIONS: High-dose opioid agonist therapy seems particularly important to reduce drug-related harms among hepatitis C virus-naive and previously infected people who inject drugs in Montreal.

Psychological and Physical Health of Nonoffending Parents After Disclosure of Sexual Abuse of Their Child.

Disclosure of child sexual abuse can be traumatic for nonoffending parents. Research has shown its impact on mothers' mental health, which includes heightened psychological distress, depression, and post-traumatic stress disorder. Very little is known, however, about its impact on their physical health or on fathers' health. The self-perceived mental and physical health of nonoffending parents after child sexual abuse disclosure was compared to determine gender-related differences in this regard. Interviews were conducted with 109 mothers and 43 fathers of 6- to 13-year-old sexually abused children. Bivariate analyses revealed that a fair proportion of parents reported psychological and physical problems after disclosure. However, proportionally more mothers than fathers reported psychological distress, depression, and use of professional services. Fathers were more likely to resort to health services instead of social services and to use medication for depression. Study findings provide leads for health and social service providers for the development of intervention protocols and referral procedures sensitive to gender issues, and they shed new light on specific needs of nonoffending parents.

Peroxiredoxin-4 interacts with and regulates the thromboxane A(2) receptor.

We identified peroxiredoxin-4 (Prx-4) as a protein interacting with the beta isoform of the thromboxane A(2) receptor (TPbeta) by yeast two-hybrid analysis. Prx-4 co-immunoprecipitated constitutively with TPbeta in HEK293 cells. The second and third intracellular loops as well as the C-terminus of TPbeta interacted directly with Prx-4. Co-expression of Prx-4 caused a 60% decrease in cell surface expression of TPbeta. Prx-4 and TPbeta predominantly co-localized in the endoplasmic reticulum. Co-expression of Prx-4 in cells treated with H(2)O(2) targeted TPbeta for degradation. We show for the first time an interaction between a receptor involved in oxidative stress and Prx-4, an anti-oxidative enzyme.

The sigma-1 receptor modulates NMDA receptor synaptic transmission and plasticity via SK channels in rat hippocampus.

The sigma receptor (sigmaR), once considered a subtype of the opioid receptor, is now described as a distinct pharmacological entity. Modulation of N-methyl-D-aspartate receptor (NMDAR) functions by sigmaR-1 ligands is well documented; however, its mechanism is not fully understood. Using patch-clamp whole-cell recordings in CA1 pyramidal cells of rat hippocampus and (+)pentazocine, a high-affinity sigmaR-1 agonist, we found that sigmaR-1 activation potentiates NMDAR responses and long-term potentiation (LTP) by preventing a small conductance Ca2+-activated K+ current (SK channels), known to shunt NMDAR responses, to open. Therefore, the block of SK channels and the resulting increased Ca2+ influx through the NMDAR enhances NMDAR responses and LTP. These results emphasize the importance of the sigmaR-1 as postsynaptic regulator of synaptic transmission.

Reduced glycine transporter type 1 expression leads to major changes in glutamatergic neurotransmission of CA1 hippocampal neurones in mice.

To investigate the effects of persistent elevation of synaptic glycine at Schaffer collateral-CA1 synapses of the hippocampus, we studied the glutamatergic synaptic transmission in acute brain slices from mice with reduced expression of glycine transporter type 1 (GlyT1+/-) as compared to wild type (WT) littermates using whole-cell patch-clamp recordings of CA1 pyramidal cells. We observed faster decay kinetics, reduced ifenprodil sensitivity and increased zinc-induced antagonism in N-methyl-d-aspartate receptor (NMDAR) currents of GlyT1+/- mice. Moreover, the ratio alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR)/NMDAR was decreased in mutants compared to WT. Surprisingly, this change was associated with a reduction in the number of AMPARs expressed at the CA1 synapses in the mutants compared to WT. Overall, these findings highlight the importance of GlyT1 in regulating glutamatergic neurotransmission.