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Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Adolescents with depression are at risk for negative long-term consequences and recurrence of depression. Many do not receive nor access treatment, especially Latino youth. New treatment approaches are needed. This study examined the feasibility and acceptability of a stepped collaborative care treatment model (SCIPT-A) for adolescents with depression utilizing interpersonal psychotherapy for adolescents (IPT-A) and antidepressant medication (if needed) compared to Enhanced Treatment as Usual (E-TAU) in urban pediatric primary care clinics serving primarily Latino youth. Results suggest the SCIPT-A model is feasible, acceptable and potentially beneficial for urban Latino adolescents. Clinicians delivered the SCIPT-A model with fidelity using supervision successfully implemented in a community setting.

A previously healthy 23-month-old girl presents with fever and a limp. She has had fever every other day for the past 2 months. Over the past 2 weeks, she has been favoring her right leg and occasionally complains of leg pain with ambulation. Today’s clinic visit was prompted by an abrupt refusal to bear weight on the left leg. Review of systems is notable for subjective weight loss, chills, and night sweats during the past month. Her immunizations are up to date, and she has no recent travel or exposure history. She takes no medications. On physical examination, the girl is alert but fussy and has growth parameters within normal limits. She is afebrile; her heart rate is 164 beats per minute, respiratory rate is 28 breaths per minute, and blood pressure while crying is 158/91 mm Hg. Her left lower extremity is held in extension and external rotation; she will not allow abduction of her hip. There is no rash, swelling, or warmth over the hip or knee joints bilaterally. She will not bear any weight on the left leg, but she moves the right leg spontaneously. She has normal results on neurovascular examination. A few scattered ecchymoses are noted on both legs. The results of the remainder of the physical examination are normal. Laboratory studies reveal a white blood cell count of 5.9 × 103/μL, without any immature cells, hemoglobin level of 8 g/dL, and platelets of 60 × 103/μL. Her C-reactive protein level is 5.7 mg/dL, and erythrocyte sedimentation rate is 90 mm/h. Radiographs of the lower extremities show demineralization and mottling at the left femoral metaphysis. Additional laboratory and imaging studies reveal the diagnosis. A 17-year-old boy with congenital heart disease (CHD) presents with a fever and fatigue. His past medical history …

BACKGROUND AND PURPOSE Single gate transcranial Doppler spectrogram (sgTCD) has a high variability in the detection of microembolic signals (MES), Adding Power M-mode Doppler (PMD) information may improve MES detection. Our study's aim is to derive combined PMD/sgTCD microemboli criteria to overcome this limitation. METHODS Patients with symptomatic carotid disease were prospectively enrolled within 24 h of symptom onset underwent 1 hour TCD emboli monitoring. We reviewed disparity between PMD MES criteria and sgTCD MES criteria. We compared combined PMD/sgTCD criteria to sgTCD alone criteria by measuring the intraclass correlation coefficient (ICC). RESULTS Of 92 patients, 28 patients had evidence of MES on sgTCD or PMD. Total MES count was 269 based on sgTCD criteria, and 326 based on combined PMD/sgTCD criteria (P= 0.005). Combined PMD/sgTCD criteria revealed 17 MESs (4.8%) based on sgTCD criteria to represent artifacts and 57 MESs (17.5%) not to be detected by sgTCD criteria. Overall ICC based on sgTCD criteria was 0.67 [95% confidence interval (CI): 0.58–0.74]; however, introducing combined PMD/sgTCD criteria resulted in a significant increase in the ICC, 0.91 (95% CI: 0.88–0.93). CONCLUSION Our combined PMD/sgTCD criteria for MES appeared to improve the yield of MES detection. Reliability in MES detection interpretation was improved when combined PMD/sgTCD criteria was applied.

Background:In the emergency department, portable point-of-care testing (POCT) coagulation devices may facilitate stroke patient care by providing rapid International Normalized Ratio (INR) measurement. The objective of this study was to evaluate the reliability, validity, and impact on clinical decision-making of a POCT device for INR testing in the setting of acute ischemic stroke (AIS).Methods:A total of 150 patients (50 healthy volunteers, 51 anticoagulated patients, 49 AIS patients) were assessed in a tertiary care facility. The INR’s were measured using the Roche Coaguchek S and the standard laboratory technique.Results:The interclass correlation coefficient and 95% confidence interval between overall POCT device and standard laboratory value INRs was high (0.932 (0.69 - 0.78). In the AIS group alone, the correlation coefficient and 95% CI was also high 0.937 (0.59 - 0.74) and diagnostic accuracy of the POCT device was 94%.Conclusions:When used by a trained health professional in the emergency department to assess INR in acute ischemic stroke patients, the CoaguChek S is reliable and provides rapid results. However, as concordance with laboratory INR values decreases with higher INR values, it is recommended that with CoaguChek S INRs in the > 1.5 range, a standard laboratory measurement be used to confirm the results.

Objectif : Presenter de l'information sur les considerations speciales quand il s'agit de prescrire des inhibiteurs specifiques du recaptage de la serotonine (ISRS) antidepresseurs aux femmes. Methodes : Etude de la documentation et analyse des effets indesirables des ISRS declares a Sante Canada entre 1986 et 1996. Resultats : Les ISRS sont prescrits deux fois plus souvent aux femmes qu'aux hommes. Des considerations speciales doivent etre donnees au contexte social dans lequel la maladie apparait, aux aspects biologiques de la maladie, aux effets des steroides sexuels endogenes et exogenes, aux menstruations, a la grossesse, a l'allaitement et a la menopause. Les effets secondaires graves ou mortels sont le plus souvent causes par une interaction medicament-medicament ou alcool-medicament. Les effets secondaires endocriniens sont plus frequents chez les femmes que chez les hommes. Conclusions : Bien que les ISRS prescrits aux femmes soient relativement efficaces et surs, il faut une recherche plus poussee pour le suivi a long terme des enfants exposes a ces medicaments durant la grossesse ou l'allaitement. Il faut egalement poursuivre l'etude des effets des steroides sexuels sur la pharmacodynamique et la cinetique. Enfin, il faut surveiller de facon continue les effets secondaires et en rendre compte. Pour une surete maximale, il faut donner des considerations speciales aux effets secondaires endocriniens et a l'interaction medicament-medicament ou alcool-medicament.

Over two thirds of people suffering from depression complain of pain with or without reporting psychological symptoms. Many people have trouble expressing internal emotions, consider mental illness to be a stigma, or simply assume depressive symptoms relate to their personal situations and therefore do not seek treatment. Physical symptoms are more prevalent among women, the elderly, the poor, children, culturally diverse populations, the medically ill, and the imprisoned. Because of a dual mechanism of action, medications such as duloxetine and venlafaxine may be useful in treating the physical symptoms as well as depressive symptoms in these special populations.

BACKGROUND: The assessment of the psychosocial health of pregnant women and their families, although recommended, is not carried out by most practitioners. One reason is the lack of a practical and evidence-based tool. In response, a multidisciplinary group created the Antenatal Psychosocial Health Assessment (ALPHA) form. This article describes the development of this tool and experience with it in an initial field trial. METHODS: A systematic literature review revealed 15 antenatal psychosocial risk factors associated with poor postpartum family outcomes of woman abuse, child abuse, postpartum depression, marital/couple dysfunction and increased physical illness. The ALPHA form, incorporating these risk factors, was developed and refined through several focus groups. It was then used by 5 obstetricians, 10 family physicians, 7 midwives and 4 antenatal clinic nurses in various urban, rural and culturally diverse locations across Ontario. After 3 months, these health care providers met in focus groups to discuss their experiences. A sample of pregnant women assessed using the ALPHA form were interviewed about their experience as well. Results were analysed according to qualitative methods. RESULTS: The final version of the ALPHA form grouped the 15 risk factors into 4 categories--family factors, maternal factors, substance abuse and family violence--with suggested questions for each area of enquiry. The health care providers uniformly reported that the form helped them to uncover new and often surprising information, even when the women were well known to them. Incorporating the form into practice was usually accomplished after a period of familiarization. Most of the providers said the form was useful and would continue to use it if it became part of standard care. The pregnant women in the sample said they valued the enquiry and felt comfortable with the process, unless there were large cultural barriers. INTERPRETATION: The ALPHA form appears to be an important tool in assessing psychosocial health in pregnancy and to be readily integrated into practice. More study is required to quantify the number of risks identified and resources used, to determine the form's reliability and validity and, ultimately, to assess the effect of its use on postpartum outcomes.

There is a greatly increased risk of a woman developing a psychiatric illness requiring hospital admission during the early postpartum period. Admission of the mother has usually meant separating her from her infant at a time when bonding and attachment are developing. Nearly 40 years ago English psychiatrists began admitting infants with their mentally ill mothers, and although the theoretical basis for this is sound, there are few systematic studies of the practical problems encountered, or the outcomes. This paper compares a group of 32 psychiatrically ill postpartum women who were admitted to a Canadian general hospital psychiatric unit with their infants to a group of 26 psychiatrically ill postpartum women hospitalized on the same unit who refused admission of their infants. The women admitted with their infants were more likely to be older, living with the infants' father, in a stable residence and job, in hospital for a longer time, and caring for their babies at 2 year follow-up in contrast to the women who were admitted without their infants. The two groups were diagnostically different with joint admission mothers likely to suffer from an affective psychotic illness, while the mothers without infants were more likely to suffer from personality disorder or substance abuse. The effects of mother-infant admission and some of the practical problems encountered are discussed.

"Twentieth-century disease", or "total allergy syndrome", is a condition attributed to hypersensitivity to the environment that may sometimes be seen as so serious that the patient is incapable of living in the modern world. Although the popular media frequently carry stories about it, there is little scientific literature. It is diagnosed by clinical ecologists, who maintain, among other theories, that susceptible individuals experience an overload in assaults by artificial materials in the environment. The patients usually have multiple ill defined symptoms for which no organic cause can be found, but they vigorously resist psychiatric referral, as they attribute their symptoms to allergy. A group of 18 patients who were purportedly suffering from 20th-century disease were referred to a university psychiatric consultation liaison service. They virtually all had a long history of visits to physicians, and their symptoms were characteristic of several well known psychiatric disorders. The case histories and management of three of them are presented. Although this group of patients may have been atypical in that they had more severe psychologic symptoms, the experience indicates that a psychiatric diagnosis ought to be considered. The symptoms of 20th-century disease have much in common with other conditions known to physicians for centuries.