Identifying perceptions and barriers regarding vaccination in patients with rheumatoid arthritis: A Canadian perspective.

AIM: Canadian guidelines recommend that patients with rheumatoid arthritis (RA) receive pneumococcal, influenza and shingles vaccinations. The aim of this study was to identify and understand vaccination rates in Canadian patients with RA. METHODS: We conducted an observational study to evaluate uptake of herpes zoster (HZ), influenza and pneumonia vaccination in a cross-section of patients with RA in Kingston, Ontario, Canada. Data were collected using a self-administered questionnaire in patients attending at an academic rheumatology clinic. If vaccination was not received, the reason was established. RESULTS: Ninety-eight out of a total of 103 patients surveyed met the inclusion criteria and were evaluated: 72.4% had received the influenza vaccination in the past year encompassing a period of 2017-2019. Of the 27.6% who did not, the most common chosen reason was personal preference not to get vaccinated (55.6%). Regarding HZ, 18.4% had received vaccination. Of the 2 available types of vaccines, more participants received Zostavax (66.7%) as compared to Shringrix (33.3%). For those not vaccinated (81.6%), "Other" was the most chosen option (37.5%) with the reasons subsequently specified as cost, concern over interaction with treatment and waiting until age ≥65 years. In terms of pneumococcal vaccination, 36.7% were vaccinated, with the majority being vaccinated with Pneumovax-23 (63.9%) compared to Prevnar-13 (16.7%) or both (19.4%). Of the 63.3% of the participants who did not receive vaccination, the most cited reason was they did not know they should receive pneumococcal vaccination (48.4%). CONCLUSIONS: Vaccination rates among Canadian patients with RA are suboptimal.

Use of incisional vacuum-assisted closure in the prevention of postoperative infection in high-risk patients who underwent spine surgery: a proof-of-concept study.

OBJECTIVE: This proof-of-concept study was conducted to determine whether negative-pressure wound therapy, through the use of incisional vacuum-assisted closure (VAC), is associated with a reduction in surgical site infections (SSIs) when compared to standard wound dressings in patients undergoing open posterior spinal fusion who have a high risk of infection. METHODS: A total of 64 patients were examined; 21 patients received incisional VAC application (VAC group) versus 43 diagnosis-matched patients who received standard wound dressings (control group). Patients in the VAC group were prospectively enrolled in a consecutive series between March 2013 and March 2014 if they met the following diagnostic criteria for high risk of infection: posterior open surgery across the cervicothoracic junction; thoracic kyphosis due to metastatic disease; high-energy trauma; or multilevel revision reconstructive surgery. Patients in the VAC group also met one or more comorbidity criteria, including body mass index ≥ 35 or < 18.5, diabetes, previous radiation at surgical site, chemotherapy, steroid use, bedridden state, large traumatic soft-tissue disruption, or immunocompromised state. Consecutive patients in the control group were retrospectively selected from the previous year by the same high-risk infection diagnostic criteria as the VAC group. All surgeries were conducted by the same surgeon at a single site. The primary outcome was SSI. All patients had 1 year of follow-up after their surgery. Baseline demographics, intraoperative parameters, and postoperative wound infection rates were compared between groups. RESULTS: Patient demographics including underlying comorbidities were similar, with the exception that VAC-treated patients were malnourished (p = 0.020). VAC-treated patients underwent longer surgeries (p < 0.001) and required more postoperative ICU admissions (p = 0.039). The median length of hospital stay was not different between groups. In total, 9 control patients (21%) developed an SSI, versus 2 VAC-treated patients (10%). CONCLUSIONS: Patients in this cohort were selected to have an increased risk of infection; accordingly, the rate of SSI was high. However, negative-pressure wound therapy through VAC application to the postoperative incision resulted in a 50% reduction in SSI. No adverse effects were noted secondary to VAC application. The preliminary data confirm the authors' proof of concept and strongly support the need for a prospective randomized trial.

Associations between patient expectations of joint arthroplasty surgery and pre- and post-operative clinical status.

Improvements in implant materials and designs have broadened surgical indications and improved the technical successes of joint arthroplasty surgery. Nevertheless, a small but notable proportion of patients remain dissatisfied despite technically successful surgery. Given reported associations between unfulfilled patient expectations and dissatisfaction, we performed a systematic review to investigate the current state of knowledge concerning potential associations between clinical status and patient expectations of joint arthroplasty procedures. A wide range of expectation assessment instruments was identified, some of which assessed probabilistic expectations and other value-based expectations. Consistent associations were identified between probabilistic expectations of surgery and better pre-operative disease-specific and general health status, as well as more desirable post-operative disease specific scores. In contrast, no consistent associations were identified between clinical status and value-based expectations. Fulfillment of expectations was consistently associated with superior disease-specific and general health absolute and change scores, irrespective of the expectations paradigm used.

PAOPA, a potent dopamine D2 receptor allosteric modulator, prevents and reverses behavioral and biochemical abnormalities in an amphetamine-sensitized preclinical animal model of schizophrenia.

Allosteric modulators are emerging as new therapeutics for the treatment of psychiatric illnesses, such as schizophrenia. Conventional antipsychotic drugs are typically dopamine D2 receptor antagonists that compete with endogenous dopamine at the orthosteric site, and block excessive dopamine neurotransmission in the brain. However, they are unable to treat all symptoms of schizophrenia and often cause adverse motor and metabolic side effects. The binding profile of allosteric modulators differs, as they interact with their receptor at a novel binding site and their activity is determined by physiological signaling. In collaboration, our laboratories have synthesized and evaluated over 185 compounds for their allosteric modulatory activity at the dopamine D2 receptor. Of these compounds, PAOPA is among the most potent allosteric modulators, and has been shown to be effective in treating the MK-801 induced preclinical animal model of schizophrenia. The objective of this study was to evaluate PAOPA's ability to prevent and reverse behavioral abnormalities in an amphetamine-sensitized preclinical animal model of schizophrenia. Amphetamine sensitized rats were given PAOPA during sensitization and following sensitization to determine whether PAOPA is able to prevent and reverse behavioral abnormalities. Furthermore, changes in post-mortem dopamine levels were measured by high performance liquid chromatography in various brain regions. The results presented demonstrate that PAOPA is able to prevent and reverse behavioral and biochemical abnormalities in an amphetamine-sensitized animal model of schizophrenia.

Behavioral effects of non-viral mediated RNA interference of synapsin II in the medial prefrontal cortex of the rat.

Synapsin II is a synaptic vesicle-associated phosphoprotein that has been implicated in the pathophysiology of schizophrenia. Researchers have demonstrated reductions in synapsin II mRNA and protein in post-mortem prefrontal cortex and hippocampus samples from patients with schizophrenia. Synapsin II protein expression has been shown to be regulated by dopamine D(1) and D(2) receptor activation. Furthermore, behavioral testing of the synapsin II knockout mouse has revealed a schizophrenic-like behavioral phenotype in this mutant strain, suggesting a relationship between dysregulated and/or reduced synapsin II and schizophrenia. However, it remains unknown the specific regions of the brain of which perturbations in synapsin II play a role in the pathophysiology of this disease. The aim of this project was to evaluate animals with a selective knock-down of synapsin II in the medial prefrontal cortex through the use of siRNA technology. Two weeks after continuous infusion of synapsin II siRNAs, animals were examined for the presence of a schizophrenic-like behavioral phenotype. Our results reveal that rats with selective reductions in medial prefrontal cortical synapsin II demonstrate deficits in sensorimotor gating (prepulse inhibition), hyperlocomotion, and reduced social behavior. These results implicate a role for decreased medial prefrontal cortical synapsin II levels in the pathophysiology of schizophrenia and the mechanisms of aberrant prefrontal cortical circuitry, and suggest that increasing synapsin II levels in the medial prefrontal cortex may potentially serve as a novel therapeutic target for this devastating disorder.

Medial prefrontal cortical synapsin II knock-down induces behavioral abnormalities in the rat: examining synapsin II in the pathophysiology of schizophrenia.

Synapsin II is a synaptic vesicle-associated phosphoprotein that has been implicated in the pathophysiology of schizophrenia. Studies have demonstrated reductions in synapsin II mRNA and protein in medial prefrontal cortical post-mortem samples from patients with schizophrenia, genetic associations between synapsin II and schizophrenia, and synapsin II protein regulation by dopamine receptor activation. Collectively, this research indicates a relationship between synapsin II dysregulation and schizophrenia; however, it remains unknown whether perturbations in synapsin II play a role in the pathophysiology of this disease. The aim of this project was to evaluate animals with selective knock-down of synapsin II in the medial prefrontal cortex. After continuous infusion of synapsin II antisense sequences, animals were examined for the presence of schizophrenic-like behavioral phenotypes and assessed on the response to clinically relevant antipsychotic drugs. Our results indicate that rats with selective reductions in medial prefrontal cortical synapsin II demonstrate deficits in sensorimotor gating (prepulse inhibition), reduced social behavior, and hyperlocomotion, which are corrected by the atypical antipsychotic drug olanzapine. Additionally, synapsin II knock-down disrupts serial search efficiency. These behavioral changes are accompanied by reductions in vesicular neurotransmitter transporter protein concentrations for glutamate (VGLUT1 and VGLUT2) and GABA (VGAT), without affecting dopamine (VMAT2). These results implicate a causal role for decreased synapsin II in the medial prefrontal cortex in the pathophysiology of schizophrenia and the mechanisms of aberrant prefrontal cortical circuitry, and suggest that synapsin II may potentially serve as a novel therapeutic target for this disorder.