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Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder ( n =159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry (‘0-weeks’ group) or (ii) at 24 weeks after entry (‘24-weeks’ group) or (iii) continuation of risperidone or olanzapine for the full duration of the study (‘52-weeks’ group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.

Background: The diagnosis of urinary tract infection (UTI) is made based on symptoms, urinalysis and urine culture. While simple urinary tract infections do not require routine culture, the Infectious Disease Society of America (IDSA) Guidelines state that complicated urinary tract infections should have urine cultures performed to determine which antibiotics are effective, as there is a higher risk of infection with resistant organisms. We hypothesized that the rate of urine cultures sent for complicated UTI is less than is recommended by the literature. Aim Statement: We aimed to implement a follow-up reporting system for Urinary Culture in patients diagnosed with complicated UTIs and raise our Urinary Culture rates in this population to 80% by June 2019. Measures & Design: We performed a single-center chart review using Emergency Department (ED) charts of non-admitted patients. They were audited daily for two weeks to obtain a sample of patients who had a discharge diagnosis of urinary tract infection, pyelonephritis or cystitis. Charts capturing these diagnoses were assessed to see if a culture was clinically indicated and if it was ordered. Charts were screened for the presence of any of the following criteria indicating complicated UTI: known structural or functional abnormality of the urinary tract, genitourinary obstruction, pregnancy, immunosuppression, diabetes, indwelling or intermittent catheter use, fever, male patient, clinical pyelonephritis, antimicrobial failure, or transfer from a nursing home. Data was then compiled to determine culture rates in complicated and uncomplicated UTIs. This prevalence rate established the baseline performance in the ED which was used to inform the quality improvement project. Evaluation/Results: Over a two week period, 26 patients were discharged from the ED with a diagnosis of UTI, with 17 of these patients meeting criteria for complicated UTI. Only 6 of 17 complicated UTIs were sent for urine culture, therefore our pre-implementation culture rate was 35%. After initial data collection, a follow-up system was designed ensuring that urine culture and sensitivities results would be compiled and reviewed daily at Hamilton Health Sciences. This system was created with input from key stakeholders including department chiefs, core lab services, ED physicians and business clerks. A discrepancy form was created for documentation of culture result recognition and any required patient follow up ie. antibiotic change. In October 2019, the system had been implemented for a month, after which another chart review was completed. 27 cases were captured, 18 of which were complicated. The complicated culture rate had increased significantly from 35% to 72%. Discussion/Impact: In the ED, ordering of cultures for patients being discharged, regardless of type, is commonly associated with concern of result follow up, which may take up to 72 hours. This discrepancy system was implemented to ensure that all urine cultures ordered had appropriate follow up, thus supporting physicians in ordering cultures when indicated. The significant improvement in culture rate from 35% to 72% is balanced by one single culture of all 9 simple UTIs (11%). In PDSA cycle 2, we hope to increase rates to 90% by improving current challenges with the system.

Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n = 159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, subgroup analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.

In the UK an aging population is resulting in more people being diagnosed with cancer, and an increasing number of treatment options means that many patients live significantly longer with their disease. It is anticipated therefore that an increasing number of patients will present to primary and secondary care with acute complications of cancer, or the treatment thereof. Many doctors have limited experience in managing patients with cancer and acute oncological emergencies. This article reviews the diagnosis and management of four common oncological emergencies: febrile neutropenia, metastatic spinal cord compression, superior vena cava obstruction, and malignancy associated hypercalcaemia. It is vital to recognise these conditions, as failure to implement immediate and appropriate treatment may result in significant morbidity or death.

The first enantioselective organocatalytic α-allylation of cyclic ketones has been accomplished via singly occupied molecular orbital catalysis. Geometrically constrained radical cations, forged from the one-electron oxidation of transiently generated enamines, readily undergo allylic alkylation with a variety of commercially available allyl silanes. A reasonable latitude in both the ketone and allyl silane components is readily accommodated in this new transformation. Moreover, three new oxidatively stable imidazolidinone catalysts have been developed that allow cyclic ketones to successfully participate in this transformation. The new catalyst platform has also been exploited in the first catalytic enantioselective α-enolation and α-carbooxidation of ketones.

Postoperative dental pain is pervasive and can affect a patient's quality of life. Adopting a patient-centric approach to pain management involves having contemporaneous information about the patient's experience of pain and using it to personalize care. In this study, we evaluated the use of a mobile health (mHealth) platform to collect pain-related patient-reported outcomes over 7 days after the patients underwent pain-inducing dental procedures; we then relayed the information to the dentist and determined its impact on the patient's pain experience. The study used a cluster-randomized experimental study design with an intervention arm where patients were prompted to complete a series of questions relating to their pain experience after receiving automated text notifications on their smartphone on days 1, 3, 5, and 7, with the resulting information fed back to dentists, and a control arm where patients received usual care. Providers were randomized, and patients subsequently assumed the enrollment status of their providers. Providers or their staff identified eligible patients and invited them to participate in the study. Provider interviews and surveys were conducted to evaluate acceptance of the mHealth platform. A total of 42 providers and 1525 patients participated. For the primary outcome (pain intensity on a 1 to 10 scale, with 10 being the most painful), intervention group patients reported an average pain intensity of 4.8 (SD 2.6), while those in the control group reported an average pain intensity of 4.7 (SD 2.8). These differences were not significant. There were also no significant differences in secondary outcomes, including pain interference with activity or sleep, patient satisfaction with pain management, or opioid prescribing. Patient surveys revealed reluctance to use the app was mostly due to technological challenges, data privacy concerns, and a preference for phone calls over texting. Providers had high satisfaction with the app and suggested integrating additional features, such as an in-system camera for patients to upload pictures and videos of the procedural site, and integration with the electronic health record system. While the mHealth platform did not have a significant impact on acute postoperative pain experience, patients and providers indicated improvement in patient-provider communication, patient-provider relationship, postoperative complication management, and ability to manage pain medication prescribing. Expanded collaboration between mHealth developers and frontline health care providers can facilitate the applicability of these platforms, further help improve its integration with the normal clinic workflow, and assist in moving toward a more patient-centric approach to pain management.

IntroductionSARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.Methods and analysisCanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.Ethics and disseminationThe CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).Trial registration numberNCT05614349

Many users search the Internet for answers to health questions. Complementary and alternative medicine (CAM) is a particularly common search topic. Because many CAM therapies do not require a clinician's prescription, false or misleading CAM information may be more dangerous than information about traditional therapies. Many quality criteria have been suggested to filter out potentially harmful online health information. However, assessing the accuracy of CAM information is uniquely challenging since CAM is generally not supported by conventional literature. The purpose of this study is to determine whether domain-independent technical quality criteria can identify potentially harmful online CAM content. We analyzed 150 Web sites retrieved from a search for the three most popular herbs: ginseng, ginkgo and St. John's wort and their purported uses on the ten most commonly used search engines. The presence of technical quality criteria as well as potentially harmful statements (commissions) and vital information that should have been mentioned (omissions) was recorded. Thirty-eight sites (25%) contained statements that could lead to direct physical harm if acted upon. One hundred forty five sites (97%) had omitted information. We found no relationship between technical quality criteria and potentially harmful information. Current technical quality criteria do not identify potentially harmful CAM information online. Consumers should be warned to use other means of validation or to trust only known sites. Quality criteria that consider the uniqueness of CAM must be developed and validated.

Cisplatin (CDDP) is a chemotherapeutic agent widely used to treat solid tumours. We present a case of reversible CDDP-associated branch retinal artery occlusion.Cisplatin (CDDP) is a chemotherapeutic agent widely used to treat solid tumours. We present a case of reversible CDDP-associated branch retinal artery occlusion.