North York General Hospital

This paper presents PRECIS-2-a validated, improved version of the tool-together with guidance for how to use it PRECIS-2 has nine domains including three new ones (recruitment, setting, and organisation), each scored on a 5-point Likert continuum (from 1=very explanatory "ideal conditions" to 5=very pragmatic "usual care conditions") so that trialists, clinicians, and policymakers can more easily consider whether design decisions match their intended purpose on 2 August

Healthcare workers (HCWs) found the 2003 outbreak of severe acute respiratory syndrome (SARS) to be stressful, but the long-term impact is not known. From 13 to 26 months after the SARS outbreak, 769 HCWs at 9 Toronto hospitals that treated SARS patients and 4 Hamilton hospitals that did not treat SARS patients completed a survey of several adverse outcomes. Toronto HCWs reported significantly higher levels of burnout (p = 0.019), psychological distress (p<0.001), and posttraumatic stress (p<0.001). Toronto workers were more likely to have reduced patient contact and work hours and to report behavioral consequences of stress. Variance in adverse outcomes was explained by a protective effect of the perceived adequacy of training and support and by a provocative effect of maladaptive coping style and other individual factors. The results reinforce the value of effective staff support and training in preparation for future outbreaks.

I. Introduction 1. Introduction to the Approach 2. A Process Facilitative Approach to Therapy II. Theory: Emotion and Cognition in Change 3. Perspectives on Human Functioning 4. Towards an Experiential Theory of Functioning 5. Dysfunction III. The Manual: Basic Principles and Task-Guided Interventions 1. Treatment Manual: The General Approach 6. Treatment Principles for a Process Experiential Approach 7. What the Therapist Does: Experiential Response Intentions and Modes 2. The Treatment Tasks 8. Systematic Evocative Unfolding at a Marker of a Problematic Reaction Point 9. Experiential Focusing for an Unclear Felt Sense 10. Two Chair Dialogue at a Self-Evaluative Split 11. Two Chair Enactment for Self-Interruption Split 12. Empty-Chair Work and Unfinished Business 13. Empathic Affirmation at a Marker of Intense Vulnerability IV. Conclusion 14. Applying the Process Experiential Approach 15. The Process Experiential Approach: An Overview, Research, Theory, and the Future

An understanding of how T cell memory is maintained is crucial for the rational design of vaccines. Memory T cells were shown to persist indefinitely in major histocompatibility complex (MHC) class I-deficient mice and retained the ability to make rapid cytokine responses upon reencounter with antigen. In addition, memory CD8 T cells, unlike naïve cells, divided without MHC-T cell receptor interactions. This "homeostatic" proliferation is likely to be important in maintaining memory T cell numbers in the periphery. Thus, after naïve CD8 T cells differentiate into memory cells, they evolve an MHC class I-independent "life-style" and do not require further stimulation with specific or cross-reactive antigen for their maintenance.

BACKGROUND: Some copy-number variants are associated with genomic disorders with extreme phenotypic heterogeneity. The cause of this variation is unknown, which presents challenges in genetic diagnosis, counseling, and management. METHODS: We analyzed the genomes of 2312 children known to carry a copy-number variant associated with intellectual disability and congenital abnormalities, using array comparative genomic hybridization. RESULTS: Among the affected children, 10.1% carried a second large copy-number variant in addition to the primary genetic lesion. We identified seven genomic disorders, each defined by a specific copy-number variant, in which the affected children were more likely to carry multiple copy-number variants than were controls. We found that syndromic disorders could be distinguished from those with extreme phenotypic heterogeneity on the basis of the total number of copy-number variants and whether the variants are inherited or de novo. Children who carried two large copy-number variants of unknown clinical significance were eight times as likely to have developmental delay as were controls (odds ratio, 8.16; 95% confidence interval, 5.33 to 13.07; P=2.11×10(-38)). Among affected children, inherited copy-number variants tended to co-occur with a second-site large copy-number variant (Spearman correlation coefficient, 0.66; P<0.001). Boys were more likely than girls to have disorders of phenotypic heterogeneity (P<0.001), and mothers were more likely than fathers to transmit second-site copy-number variants to their offspring (P=0.02). CONCLUSIONS: Multiple, large copy-number variants, including those of unknown pathogenic significance, compound to result in a severe clinical presentation, and secondary copy-number variants are preferentially transmitted from maternal carriers. (Funded by the Simons Foundation Autism Research Initiative and the National Institutes of Health.).

BACKGROUND: Breast-conservation surgery is now commonly used to treat breast cancer. Postoperative breast irradiation reduces cancer recurrence in the breast. There is still controversy concerning the necessity of irradiation of the breast in all patients. PURPOSE: We present an update of results from a randomized clinical trial designed to examine the efficacy of breast irradiation following conservation surgery in the treatment of women with axillary lymph node-negative breast cancer. The patients were enrolled from April 1984 through February 1989. Initial results were published in 1992 after a median follow-up time of 43 months. It was reported that recurrence of cancer in the breast occurred in 5.5% of the patients who received breast irradiation compared with 25.7% of those who did not. No difference in survival was detected between the two treatment groups. Now that the median patient follow-up has reached 7.6 years, the trial end points have been re-examined and an attempt has again been made to identify a group of patients at low risk for recurrence of cancer in the breast. METHODS: Eight hundred thirty-seven patients with node-negative breast cancer were randomly assigned to receive either radiation therapy (n = 416) or no radiation therapy (n = 421) following lumpectomy and axillary lymph node dissection. The cumulative local recurrence rate as a first event, distant recurrence (i.e., occurrence of metastasis) rate, and overall mortality rate for the treatment groups were described by the Kaplan-Meier method and compared with the use of the logrank test. The Cox proportional hazards model was used to adjust the observed treatment effect for the influence of various prognostic factors (patient age, tumor size, estrogen receptor level, and tumor histology) at study entry on the outcomes of local breast recurrence, distant recurrence, and overall mortality. All P values resulted from the use of two-tailed statistical tests. RESULTS: One hundred forty eight (35%) of the nonirradiated patients and 47 (11%) of the irradiated patients developed recurrent cancer in the breast (relative risk for patients in the former versus the latter group = 4.0; 95% confidence interval = 2.83-5.65; P < .0001). Ninety-nine (24%) of the patients in the former group have died compared with 87 (21%) in the latter group. Age (< 50 years), tumor size (> 2 cm), and tumor nuclear grade (poor) continued to be important predictors for local breast relapse. On the basis of these factors, we were unable to identify a subgroup of patients with a very low risk for local breast cancer recurrence. Tumor nuclear grade, as previously reported, and tumor size were important predictors for mortality. CONCLUSIONS: Breast irradiation was shown to reduce cancer recurrence in the breast, but there was no statistically significant reduction in mortality. A subgroup of patients with a very low risk for local breast recurrence who might not require radiation therapy was not identified.

Abstract Cognitive sex differences have remained a prominent topic in psychology for several decades, and one of the most consistent findings has been superior performance for males on tests of spatial abilities. Earlier attempts to account for this difference dealt mainly with socialization practices (Maccoby &amp; Jacklin, 1974), but the generality of the phenomenon across populations and situations led to a shift in emphasis to genetic determinants. Relationships have been found for both sexes between spatial performance and hormonal variables, measured or manipulated directly or inferred from correlates such as pubertal status, physical characteristics, menstrual cycle phase, and atypical androgen levels associated with medical disorders. Additionally, similar spatial sex differences have been found in infrahuman species.

The preliminary results of an international collaborative study examining premature menopause in fragile X carriers are presented. A total of 760 women from fragile X families was surveyed about their fragile X carrier status and their menstrual and reproductive histories. Among the subjects, 395 carried a premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three (16%) of the premutation carriers had experienced menopause prior to the age of 40 compared with none of the full mutation carriers and one (0.4%) of the controls. Based on these preliminary data, there is a significant association between fragile X premutation carrier status and premature menopause.

STUDY DESIGN: Cross-section observational study of incident spinal fractures using an administrative data-base. OBJECTIVES: To identify and define all patients who have spinal fractures within a complete population. SUMMARY OF BACKGROUND DATA: The true incidence of spinal column and cord injury is not known. Previous studies have been institutional or practice based. Accurate information concerning the magnitude of the spinal injury population and their characteristics may provide more rational basis for public health decision making and resource allocation. METHODS: The study dates were April 1, 1981 to March 31, 1984. Using the Manitoba Health Services Insurance Plan database, all patients with ICD-9-CM coding of 805.x and 806.x (spinal column fracture with and without spinal cord injury) were identified. Incidence rates, age and gender distribution, and ambulatory and hospital contracts were identified. Hospital discharge abstracts were used to classify mechanisms of injury, associated injuries, and length of stay. RESULT: The annual incidence rate of spinal fracture was 64 per 100,000. Two thousand sixty-three patients were identified, with 944 being admitted to the hospital. There were two peaks of incidence occurring in young men and elderly women. Of the hospitalized patients, 182 had cervical injury, 286 had thoracic fracture, and 403 had injury in the lumbosacral spine Associated injuries occurred in 38% of hospitalized patients. Length of stay was an average of 38.5 days. Overall mortality was 41%. Neurologic injury occurred in 122 patients. CONCLUSIONS: Ambulatory care of spine injuries is more common than hospital care. Two peaks of incidence occur-in young men and elderly women. Future decisions for research, public health policy, and resource allocation can be based on these data.

BACKGROUND: Adults with intellectual disabilities have increased early mortality compared with the general population. However, their extent of multimorbidity (two or more additional conditions) compared with the general population is unknown, particularly with regards to physical ill-health, as are associations between comorbidities, neighbourhood deprivation, and age. METHODS: We analysed primary health-care data on 1,424,378 adults registered with 314 representative Scottish practices. Data on intellectual disabilities, 32 physical, and six mental health conditions were extracted. We generated standardised prevalence rates by age-groups, gender, and neighbourhood deprivation, then calculated odds ratio (OR) and 95 % confidence intervals (95 % CI) for adults with intellectual disabilities compared to those without, for the prevalence, and number of condition. RESULTS: Eight thousand fourteen (0.56 %) had intellectual disabilities, of whom only 31.8 % had no other conditions compared to 51.6 % without intellectual disabilities (OR 0.26, 95 % 0.25-0.27). The intellectual disabilities group were significantly more likely to have more conditions, with the biggest difference found for three conditions (10.9 % versus 6.8 %; OR 2.28, 95 % CI 2.10-2.46). Fourteen physical conditions were significantly more prevalent, and four cardiovascular conditions occurred less frequently, as did any cancers, and chronic obstructive pulmonary diseases. Five of the six mental health conditions were significantly more prevalent. For the adults with intellectual disabilities, no gradient was seen in extent of multimorbidity with increasing neighbourhood deprivation; indeed findings were similar in the most affluent and most deprived areas. Co-morbidity increased with age but is highly prevalent at all ages, being similar at age 20-25 to 50-54 year olds in the general population. CONCLUSIONS: Multi-morbidity burden is greater, occurs at much earlier age, and the profile of health conditions differs, for adults with intellectual disabilities compared with the general population. There is no association with neighbourhood deprivation; people with intellectual disabilities need focussed services irrespective of where they live, and at a much earlier age than the general population. They require specific initiatives to reduce inequalities.

Recombination between repeated sequences at various loci of the human genome are known to give rise to DNA rearrangements associated with many genetic disorders. Perhaps the most extensively characterized genomic region prone to rearrangement is 17p12, which is associated with the peripheral neuropathies, hereditary neuropathy with liability to pressure palsies (HNPP) and Charcot-Marie-Tooth disease type 1A (CMT1A;ref. 2). Homologous recombination between 24-kb flanking repeats, termed CMT1A-REPs, results in a 1.5-Mb deletion that is associated with HNPP, and the reciprocal duplication product is associated with CMT1A (ref. 2). Smith-Magenis syndrome (SMS) is a multiple congenital anomalies, mental retardation syndrome associated with a chromosome 17 microdeletion, del(17)(p11.2p11.2) (ref. 3,4). Most patients (>90%) carry deletions of the same genetic markers and define a common deletion. We report seven unrelated patients with de novo duplications of the same region deleted in SMS. A unique junction fragment, of the same apparent size, was identified in each patient by pulsed field gel electrophoresis (PFGE). Further molecular analyses suggest that the de novo17p11.2 duplication is preferentially paternal in origin, arises from unequal crossing over due to homologous recombination between flanking repeat gene clusters and probably represents the reciprocal recombination product of the SMS deletion. The clinical phenotype resulting from duplication [dup(17)(p11.2p11.2)] is milder than that associated with deficiency of this genomic region. This mechanism of reciprocal deletion and duplication via homologous recombination may not only pertain to the 17p11.2 region, but may also be common to other regions of the genome where interstitial microdeletion syndromes have been defined.

IMPORTANCE: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS: Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS: Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES: Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS: Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE: Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01795859.

BACKGROUND: Although the conservation management of breast cancer has become a routine method of treatment in most centers, there is still considerable controversy surrounding the ultimate minimum treatment required for node-negative breast cancer to achieve adequate local control. PURPOSE: Our purpose was to assess the value of breast irradiation in reducing breast relapse following conservation surgery for node-negative breast cancer. We attempted to define low-risk groups of women for breast and distant site relapse (i.e., recurrence outside the breast) who might be spared breast irradiation or adjuvant systemic therapy. METHODS: Eight hundred thirty-seven patients were randomly assigned to receive radiation therapy or no radiation therapy following lumpectomy and axillary dissection for node-negative breast cancer. RESULTS: Breast irradiation reduced relapse in the breast from 25.7% in the controls to 5.5% in the irradiated patients. There was no difference in survival between the two groups (median follow-up, 43 months). A low-risk group (less than 5% chance of relapse in the breast without irradiation) could not be defined. Tumor size (greater than 2 cm), age (less than 40 years), and poor nuclear grade were important predictors for breast relapse. Age (less than 50 years) and poor nuclear grade were important predictors for mortality. The presence of ductal carcinoma in situ did not predict breast relapse. CONCLUSIONS: Breast irradiation significantly reduces breast relapse, but it does not influence survival. Important predictors of breast relapse are age, tumor size, and nuclear grade, but not the presence of ductal carcinoma in situ. Age and, in particular, nuclear grade predict survival. IMPLICATIONS: Further follow-up may define an acceptable low-risk group for breast relapse. Until then, we recommend that all patients receive breast irradiation. Systemic adjuvant therapy should be considered for patients with poor nuclear grade tumors.

An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole-exome sequencing (WES), are identifying the genetic basis of disease for 25-40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation-wide effort to identify mutations for childhood-onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases.

CONTEXT: Severe acute respiratory syndrome (SARS) is a new clinical entity for which no effective therapeutic strategy has been developed. OBJECTIVE: To provide preliminary results on the potential therapeutic benefit and tolerability of interferon alfacon-1 plus corticosteroids for SARS. DESIGN, SETTING, AND PATIENTS: Open-label study of 22 patients diagnosed as having probable SARS at North York General Hospital, Toronto, Ontario, between April 11 and May 30, 2003. INTERVENTIONS: Thirteen patients were treated with corticosteroids alone and 9 patients were treated with corticosteroids plus subcutaneous interferon alfacon-1. MAIN OUTCOME MEASURES: Clinical parameters, including oxygen saturation and requirement, laboratory measures, and serial chest radiography results. RESULTS: Resolution of fever and lymphopenia were similar between the 2 treatment groups. Of the 13 patients treated with corticosteroids alone, 5 (38.5%) were transferred to the intensive care unit, 3 (23.1%) required intubation and mechanical ventilation, and 1 (7.7%) died. Of the 9 patients in the interferon alfacon-1 treatment group, 3 (33.3%) were transferred to the intensive care unit, 1 (11.1%) required intubation and mechanical ventilation, and none died. The interferon alfacon-1 treatment group had a shorter time to 50% resolution of lung radiographic abnormalities (median time, 4 days vs 9 days; P =.001), had better oxygen saturation (P =.02), resolved their need for supplemental oxygen more rapidly (median, 10 days vs 16 days; P =.02), had less of an increase in creatine kinase levels (P =.03), and showed a trend toward more rapid resolution of lactate dehydrogenase levels compared with the group receiving corticosteroids alone. CONCLUSIONS: In this preliminary, uncontrolled study of patients with SARS, use of interferon alfacon-1 plus corticosteroids was associated with reduced disease-associated impaired oxygen saturation, more rapid resolution of radiographic lung abnormalities, and lower levels of creatine kinase. These findings suggest that further investigation may be warranted to determine the role of interferon alfacon-1 as a therapeutic agent for the treatment of SARS.

BACKGROUND: Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action that should minimise nerve damage. This is an update of a review first published in 2002 and last updated in 2010. OBJECTIVES: To determine the effectiveness and safety of corticosteroid therapy in people with Bell's palsy. SEARCH METHODS: On 4 March 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS. We reviewed the bibliographies of the randomised trials and contacted known experts in the field to identify additional published or unpublished trials. We also searched clinical trials registries for ongoing trials. SELECTION CRITERIA: Randomised trials and quasi-randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group receiving no therapy considered effective for this condition, unless the same therapy was given in a similar way to the experimental group. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. The main outcome of interest was incomplete recovery of facial motor function (i.e. residual facial weakness). Secondary outcomes were cosmetically disabling persistent sequelae, development of motor synkinesis or autonomic dysfunction (i.e. hemifacial spasm, crocodile tears) and adverse effects of corticosteroid therapy manifested during follow-up. MAIN RESULTS: We identified seven trials, with 895 evaluable participants for this review. All provided data suitable for the primary outcome meta-analysis. One of the trials was new since the last version of this Cochrane systematic review. Risk of bias in the older, smaller studies included some unclear- or high-risk assessments, whereas we deemed the larger studies at low risk of bias. Overall, 79/452 (17%) participants allocated to corticosteroids had incomplete recovery of facial motor function six months or more after randomisation; significantly fewer than the 125/447 (28%) in the control group (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.50 to 0.80, seven trials, n = 895). The number of people who need to be treated with corticosteroids to avoid one incomplete recovery was 10 (95% CI 6 to 20). The reduction in the proportion of participants with cosmetically disabling sequelae six months after randomisation was very similar in the corticosteroid and placebo groups (RR 0.96, 95% CI 0.40 to 2.29, two trials, n = 75, low-quality evidence). However, there was a significant reduction in motor synkinesis during follow-up in participants receiving corticosteroids (RR 0.64, 95% CI 0.45 to 0.91, three trials, n = 485, moderate-quality evidence). Three studies explicitly recorded the absence of adverse effects attributable to corticosteroids. One trial reported that three participants receiving prednisolone had temporary sleep disturbances and two trials gave a detailed account of adverse effects occurring in 93 participants, all non-serious; the combined analysis of data from these three trials found no significant difference in adverse effect rates between people receiving corticosteroids and people receiving placebo (RR 1.04, 95% CI 0.71 to 1.51, n = 715). AUTHORS' CONCLUSIONS: The available moderate- to high-quality evidence from randomised controlled trials showed significant benefit from treating Bell's palsy with corticosteroids.

PURPOSE: There is evidence that cognitive dysfunction, fatigue, and menopausal symptoms may occur in women receiving adjuvant chemotherapy for breast cancer. Here, we determine their incidence and severity, and interrelationships between them and quality of life. PATIENTS AND METHODS: In this study, 110 women receiving adjuvant chemotherapy each nominated a female relative, friend, or neighbor (matched by age) as a control; 100 eligible matched pairs were evaluated. Patients and controls completed the following assessments: the High-Sensitivity Cognitive Screen, and the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life scale with subscales for fatigue (FACT-F) and endocrine symptoms (FACT-ES). They also performed tests of attention and reaction time. RESULTS: Patients and controls were well matched for age and level of education. There was a higher incidence of moderate or severe cognitive impairment in the patient group (16% v 4%; P =.008). Patients experienced much more fatigue than controls (median FACT-F scores, 31 v 46; P <.0001) and more menopausal symptoms (median FACT-ES scores, 58 v 64; P <.0001). Self-reported quality of life of the patients was poorer than for controls, especially in physical and functional domains (median FACT-G scores, 77 v 93; P <.0001). There was strong correlation between fatigue, menopausal symptoms, and quality of life (P <.0001 for each pair), but none were significantly associated with the presence of cognitive dysfunction. CONCLUSION: Adjuvant chemotherapy causes cognitive dysfunction, fatigue, and menopausal symptoms in women with breast cancer. Priority should be given to the study of strategies that might reduce these toxic effects.

Many young children are thought by their parents to eat poorly. Although the majority of these children are mildly affected, a small percentage have a serious feeding disorder. Nevertheless, even mildly affected children whose anxious parents adopt inappropriate feeding practices may experience consequences. Therefore, pediatricians must take all parental concerns seriously and offer appropriate guidance. This requires a workable classification of feeding problems and a systematic approach. The classification and approach we describe incorporate more recent considerations by specialists, both medical and psychological. In our model, children are categorized under the 3 principal eating behaviors that concern parents: limited appetite, selective intake, and fear of feeding. Each category includes a range from normal (misperceived) to severe (behavioral and organic). The feeding styles of caregivers (responsive, controlling, indulgent, and neglectful) are also incorporated. The objective is to allow the physician to efficiently sort out the wide variety of conditions, categorize them for therapy, and where necessary refer to specialists in the field.

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Chronic postsurgical pain (CPSP), an often unanticipated result of necessary and even life-saving procedures, develops in 5-10% of patients one-year after major surgery. Substantial advances have been made in identifying patients at elevated risk of developing CPSP based on perioperative pain, opioid use, and negative affect, including depression, anxiety, pain catastrophizing, and posttraumatic stress disorder-like symptoms. The Transitional Pain Service (TPS) at Toronto General Hospital (TGH) is the first to comprehensively address the problem of CPSP at three stages: 1) preoperatively, 2) postoperatively in hospital, and 3) postoperatively in an outpatient setting for up to 6 months after surgery. Patients at high risk for CPSP are identified early and offered coordinated and comprehensive care by the multidisciplinary team consisting of pain physicians, advanced practice nurses, psychologists, and physiotherapists. Access to expert intervention through the Transitional Pain Service bypasses typically long wait times for surgical patients to be referred and seen in chronic pain clinics. This affords the opportunity to impact patients' pain trajectories, preventing the transition from acute to chronic pain, and reducing suffering, disability, and health care costs. In this report, we describe the workings of the Transitional Pain Service at Toronto General Hospital, including the clinical algorithm used to identify patients, and clinical services offered to patients as they transition through the stages of surgical recovery. We describe the role of the psychological treatment, which draws on innovations in Acceptance and Commitment Therapy that allow for brief and effective behavioral interventions to be applied transdiagnostically and preventatively. Finally, we describe our vision for future growth.