Early Intervention for Psychosis in Canada: What Is the State of Affairs?

Objective:

Early intervention services (EIS) for psychosis have been developed in several countries, including Canada. There is some agreement about the program elements considered essential for improving the long-term outcomes for patients in the early phase of psychotic disorders. In the absence of national standards, the current state of EIS for psychosis in Canada needs to be examined in relation to expert recommendations currently available.

Method:

A detailed online benchmark survey was developed and administered to 11 Canadian academic EIS programs covering administrative, clinical, education, and research domains. In addition, an electronic database and Internet search was conducted to find existing guidelines for EIS. Survey results were then compared with the existing expert recommendations.

Results:

Most of the surveyed programs offer similar services, in line with published expert recommendations (i.e., easy and rapid access, intensive follow-up through case management with emphasis on patient engagement and continuity of care, and a range of integrated evidence-based psychosocial interventions). However, differences are observed among programs in admission and discharge criteria, services for patients at ultra high risk (UHR) for psychosis, patient to clinician ratios, accessibility of services, and existence of specific inpatient units. These seem to diverge from expert recommendations.

Conclusions:

Although Canadian programs are following most expert recommendations on clinical components of care, some programs lack administrative and organizational elements considered essential. Continued mentoring and networking of clinicians through organizations such as the Canadian Consortium for Early Intervention in Psychosis (CCEIP), as well as the development of a fidelity scale through further research, could possibly help programs attain and maintain the best standards of early intervention. However, simply making clinical guidelines available to care providers is not sufficient for changing practices; this will need to be accompanied by adequate funding and support from organizations and policy makers.     

Time after excision and temperature alter ex vivo tissue relaxation time measurements

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40°C, at room temperature (28°C), or in an ice bath (4°C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40°C (20-MHz spectrometer), the T1 of liver decreased from 280 msec ± 8 to 212 msec ± 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec ± 3 to 208 msec ± 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.     

Deficits in hippocampal‐dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis

Elevated β‐amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the “transfer” of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative “transfer learning” task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APP_swePS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle β‐amyloid‐induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg‐SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal‐dependent learning may be useful for early identification of AD‐like pathology. © 2015 Wiley Periodicals, Inc.     

Selective neck dissection in node-positive squamous cell carcinoma of the head and neck

Objective The optimal type of neck dissection in head and neck squamous cell carcinoma (SCC) with clinical cervical metastases has not been determined. The following study was performed to determine the rate of regional control with selective neck dissection (SND) in these patients. Study Design Case series with planned data collection. Settings Single institution, cancer center. Methods and Subjects Patients with cervical lymph node metastases from mucosal cancers of the head and neck who were treated with SND from 2000 to 2010 were selected. Demographics, tumor characteristics, extent of neck dissection, adjuvant treatments, locoregional control, and survival were recorded. Recurrence in the neck and disease-specific survival (DSS) were primary and secondary end points. Results One hundred eight patients underwent SND. Sixty-nine (64%) were male. Median age was 62 (20-89) years. The most common primary site was the oral cavity (71.3%). Ninety-five (88%) received adjuvant treatment. Median follow-up was 21 months. Six patients (5.5%) had isolated recurrence in the dissected neck. Patients with N2C disease had poorer neck recurrence-free survival. At the end of study, 64 (59.3%) patients had no evidence of disease, and 23 (21.3%) had died of disease. Two-year DSS was 76.9%. Number of positive nodes (P = .026) and positive surgical margins (P = .001), among others, were predictors of poorer DSS. Conclusion In a highly selected group of patients with cervical lymph node metastases from head and neck SCC, selective neck dissection is effective in controlling the disease in the neck when performed in the setting of a multimodality treatment, including adjuvant radiotherapy or radiochemotherapy.     

Evaluation of autologous bone marrow in wound healing in animal model: a possible application of autologous stem cells

A study was conducted to evaluate the potential of autologous bone marrow-derived cells in comparison with buffy coat of autologous blood for rapid cutaneous wound healing in rabbit model. Three square full-thickness skin excisional wounds were created in 15 selected experimental animals (rabbit) divided randomly into three groups. The wound was treated with autologous bone marrow cells in plasma (group 1), buffy coat of blood in plasma (group 2) and autologous plasma as control (group 3). Wounds were observed for 30 days for granulation tissue formation, biochemical, histomorphological and histochemical evaluation. In this study, granulation tissue appeared significantly lesser in wounds of group 3 animals followed by group 2 and 1 animals. Neovascularisation, granulation tissue formation, denser, thicker and better arranged collagen fibres, reticulin fibres and elastin fibres formation was more in group 1 as compared with other groups. It was concluded that the application of bone marrow-derived nucleated cells into the wound margins resulted in early and significantly faster rate of complete healing as compared with buffy coat of autologous blood and autologous plasma (control). This approach may be beneficial in various surface wounds that heal at a slower rate and recommended for healing of various complicated wound in future.     

Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial

Background

Elderly patients with metastatic renal cell carcinoma (mRCC) may require special treatment considerations, particularly when comorbidities are present. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy.

Objective

To evaluate the efficacy and safety of everolimus in elderly patients (those ≥65 and ≥70 yr of age) enrolled in RECORD-1.

Design, setting, and participants

The multicenter randomized RECORD-1 phase 3 trial (Clinicaltrials.gov identifier, NCT00410124; http://www.clinicaltrials.gov) enrolled patients with mRCC who progressed during or within 6 mo of stopping sunitinib and/or sorafenib treatment (n = 416).

Intervention

Everolimus 10 mg once daily (n = 277) or placebo (n = 139) plus best supportive care. Treatment was continued until disease progression or unacceptable toxicity.

Measurements

Median progression-free survival (PFS), median overall survival (OS), and time to deterioration in Karnofsky performance status (TTD-KPS) were assessed using the Kaplan-Meier method; the log-rank test was used to compare treatment arms. Other outcomes evaluated included reduction in tumor burden, overall response rate (ORR), and safety.

Results and limitations

In RECORD-1, 36.8% of patients were ≥65 yr and 17.5% were ≥70 yr of age. PFS, OS, TTD-KPS, reduction in tumor burden, and ORR were similar in the elderly and the overall RECORD-1 population. Everolimus was generally well tolerated in elderly patients, and most adverse events were grade 1 or 2 in severity. The toxicity profile of everolimus was generally similar in older patients and the overall population; however, peripheral edema, cough, rash, and diarrhea were reported more frequently in the elderly regardless of treatment. The retrospective nature of the analyses was the major limitation.

Conclusions

Everolimus is effective and tolerable in elderly patients with mRCC. When selecting targeted therapies in these patients, the specific toxicity profile of each agent and any patient comorbidities should be considered.     

Vattikuti Institute Prostatectomy: a single-team experience of 100 cases

PURPOSE: To analyze the outcomes of the first 100 patients undergoing robotic radical prostatectomy by a single surgical team. PATIENTS AND METHODS: From August 2001 to May 2002, we performed robotic radical prostatectomy in 100 patients with localized prostate cancer. The mean age was 60 +/- 0.67 years (SEM), the body mass index 27.5 +/- 0.35, the preoperative prostate specific antigen concentration 7.2 +/- 0.86 ng/mL, and follow-up 5.5 +/- 0.24 months. Thirty-eight patients also underwent pelvic lymph node dissection. We used the da Vinci surgical system and a subperitoneal approach (the Vattikuti Institute Prostatectomy; VIP). This is a prospective outcomes analysis of these patients. RESULTS: The mean operating time was 195 +/- 5.0 minutes, and the mean blood loss was 149 +/- 11.8 mL. No patient required blood transfusion. The stages of the cancers were pT(2a) in 21, pT(2b) in 64, pT(3a) in 5, pT(3b) in 9, and pT(3b)N(1) in 1. The positive surgical margin rate was 15%. At 1, 3, and 6 months, the continence rates were 37%, 72%, and 92%, respectively, and the potency rates were 11%, 32%, and 59%. CONCLUSION: The VIP is a safe operation with excellent operative parameters, low morbidity, and good surgical margins. The early functional results are promising.     

The absence of chronic rejection in pediatric primary liver transplant patients who are maintained on tacrolimus-based immunosuppression: a long-term analysis

BACKGROUND: Although the outcome of liver transplantation has improved significantly during the past two decades, graft loss caused by chronic rejection after liver transplantation still occurs in 2% to 20% of recipients. The overall incidence of chronic rejection is also reported to be low in adult recipients, and risk factors have been identified. Chronic rejection is associated with the inability to maintain baseline immunosuppression. Additionally, the diagnoses of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, hepatitis B virus, and hepatitis C virus, common indications for liver transplantation in adults, are associated with a higher incidence of chronic rejection. Fortunately, these diagnoses are rarely seen in children. Little is known about chronic rejection in long-term pediatric liver transplant survivors. The purpose of this longitudinal study was to examine the incidence of biopsy-proven chronic rejection in long-term survivors of primary pediatric liver transplantation under tacrolimus-based immunosuppression. METHODS: From October 1989 to December 1992, 166 children (boys=95, girls=71; mean age=5.0+/-2.9 years) received a primary liver transplant. These patients were followed until March 2000 with a mean follow-up of 9+/-0.8 (range, 7.4-10.4) years. All liver biopsy specimens and explanted grafts were evaluated for evidence of chronic rejection using the International Banff Criteria. RESULTS: The mortality rate during the follow-up period was 15% (n=25). Retransplantation was required in 11% (n=18) of recipients. Actuarial patient and graft survival rates at 10 years were 84.9% and 80.1%, respectively. There were 535 liver biopsy samples available for evaluation, including the 18 explanted allografts. Biopsy specimens of three other functioning allografts showed evidence of chronic rejection. Immunosuppression had been discontinued or drastically reduced in these recipients because of life-threatening infections, noncompliance, or both. On restoring baseline immunosuppression, all three children had normalized liver function and the allografts were maintained; the liver transplant patients who are alive currently have normal liver functions. CONCLUSION: The findings of this study suggest that chronic rejection does not occur in pediatric liver transplant recipients receiving tacrolimus-based immunosuppression, provided baseline immunosuppression is maintained.     

Adolescent varicocele: association with somatometric parameters

INTRODUCTION: The developmental changes that occur as a result of puberty have been hypothesized to be important causes of varicocele. Various somatometric parameters were known to affect the occurrence of varicocele during the growth period. We conducted this study in order to examine these relationships and to determine the incidence of varicocele in adolescent males. PATIENTS AND METHODS: We evaluated 1,200 healthy males aged 0-19 years for varicocele and correlated it with the following somatometric parameters: age, height, body mass index (BMI), pubic hair distribution, penile length and testicular volume. RESULTS: Adolescent varicocele was found in 5.6% of the participants. The 13- to 19-year age-group had the highest incidence of varicocele (10.5%). Logistic regression analysis showed that the incidence was positively correlated with age, height and penile length (odds ratio 1.61, 1.04 and 1.37, respectively) and negatively correlated with left testicular volume, BMI and pubic hair distribution (odds ratio 0.87, 0.87 and 0.47, respectively). CONCLUSION: Varicocele was more prevalent in tall boys with a lower BMI, who had quickly progressed through puberty. Our observations suggest that varicocele is associated with various somatometric parameters.     

Colorectal Cancer: Postoperative Follow-up and Surveillance

Follow-up and surveillance form an important aspect of care in patients with colorectal cancers (CRC). Most recurrences will occur within 2 years of surgery and 90% by 5 years. Follow up protocols have not been well defined in stage I disease and the approach should be individualized. As 40% of patients with stages II and III will develop recurrences, intensive postoperative follow-up strategy is recommended for them. It includes visit to the clinician for clinical examination, serum carcinoembryonic antigen (CEA), computed tomography (CT) of the chest and abdomen, colonoscopy, and flexible proctosigmoidoscopy in rectal cancers. Surveillance should be undertaken in those who are medically fit for repeat surgical procedures or for chemoradiotherapy. The concept of intensive post operative surveillance is based on the fact that some of these patients can have resectable/curable recurrence.