Publications by authors named "John Maxwell"

Article Synopsis
  • TNG908 is a clinical-stage inhibitor targeting PRMT5, utilizing a unique binding mechanism that exploits the loss of the MTAP gene commonly found in various cancers.
  • It specifically inhibits PRMT5 in cancer cells lacking MTAP, which occurs in 10-15% of human cancers and could lead to more effective treatments compared to earlier drugs.
  • Ongoing Phase I/II trials are investigating the effectiveness of TNG908 in patients with MTAP-null tumors, including glioblastoma, suggesting a promising future for this therapy in multiple cancer types, particularly those affecting the brain.
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Purpose: Clinicians are often uncertain about their prognostic estimates, which may impede prognostic communication and clinical decision-making. We assessed the impact of a web-based prognostic calculator on physicians' prognostic confidence.

Methods: In this prospective study, palliative care physicians estimated the prognosis of patients with advanced cancer in an outpatient clinic using the temporal, surprise, and probabilistic approaches for 6 m, 3 m, 2 m, 1 m, 2 w, 1 w, and 3 d.

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Article Synopsis
  • PRMT5 inhibitors can target cancer cells with a specific gene deletion by utilizing the buildup of a substrate called MTA, leading to selective cell death.* -
  • TNG908 is a newly discovered and potent inhibitor that binds to the PRMT5·MTA complex, demonstrating a significant ability to kill MTAP-null cells more effectively than normal cells.* -
  • TNG908 shows promise as an oral treatment in mouse models for various tumors, including those in the central nervous system, because it can cross the blood-brain barrier.*
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Article Synopsis
  • CRISPR Cas9-based screening identifies USP1's role as a synthetic lethal target in cancers with DNA damage vulnerabilities, particularly in BRCA1/2 mutant and some wild-type tumors.
  • Inhibiting USP1 decreases DNA synthesis and causes S-phase-specific DNA damage, linked to the accumulation of mono- and polyubiquitinated PCNA.
  • This study suggests that targeting USP1 could offer a new therapeutic strategy for treating BRCA1/2 mutant tumors, as well as a subset of BRCA1/2 wild-type tumors, highlighting the importance of PCNA's posttranslational modifications.
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Introduction: Despite strong evidence from low- and middle-income countries supporting the use of task shifting to provide quality, cost-effective HIV-related health services, this strategy has been adopted less widely in high-income countries such as Canada.

Methods: In 2020, we conducted semi-structured interviews with 19 clinicians (e.g.

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Heterotopic ossification (HO) refers to ectopic bone formation, typically in residual limbs following trauma and injury. A review of injuries from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) indicated that approximately 70% of war wounds involved the musculoskeletal system, largely in part from the use of improvised explosive devices (IED) and rocket-propelled grenades (RPG). HO is reported to occur in approximately 63%-65% of wounded warriors from OIF and OEF.

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Background: Syphilis infections have been on the rise, affecting men living with HIV in urban centres disproportionately. Since individuals in HIV care undergo routine blood testing, HIV clinics provide practical opportunities to conduct regular and frequent syphilis testing. Following the implementation of a routine syphilis testing intervention in HIV outpatient clinics, we conducted a qualitative process evaluation of patient experiences to measure patient acceptability, barriers to implementation, and facilitators of successful uptake.

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Background: We implemented an opt-out clinic-based intervention pairing syphilis tests with routine human immunodeficiency virus (HIV) viral load testing. The primary objective was to determine the degree to which this intervention increased the detection of early syphilis.

Methods: The Enhanced Syphilis Screening Among HIV-Positive Men (ESSAHM) Trial was a stepped wedge cluster-randomized controlled trial involving 4 urban HIV clinics in Ontario, Canada, from 2015 to 2017.

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Pre-exposure prophylaxis (PrEP) is traditionally prescribed by HIV specialist physicians. Given finite specialist resources, there is a need to scale up PrEP delivery by decentralizing services via other healthcare professionals. We aimed to assess the feasibility of delivering PrEP to men who have sex with men (MSM) through primary care physicians and sexual health clinic nurses.

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The literature demonstrates that obtaining a biopsy of the physis may be beneficial for diagnostic purposes. A small biopsy of the epiphyseal plate may allow for earlier detection of certain conditions and be used to monitor the healing of diseased and/or damaged physes. However, due to the fear of a growth arrest in a growing child, biopsies are not currently performed.

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Gay, bisexual, and other men who have sex with men (GBM) continue to have high rates of HIV and sexually transmitted infections, including syphilis. GBM have therefore been identified by public health agencies as a high-priority population to reach with prevention initiatives. Despite the importance of mental health in preventing HIV and related infections, there is a shortage of credentialed mental health professionals to deliver behavioral Counseling interventions.

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Objective: To determine the feasibility of vaginal cuff brachytherapy (VCB) followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy (ddTC) in enriched, high-intermediate risk (H-IR) patients with early stage endometrial cancer following hysterectomy.

Methods: A phase II trial of early stage endometrial cancer patients treated with VCB (2100 cGy) followed by three cycles of carboplatin (AUC 6) and dose dense paclitaxel (80 mg/m) weekly within 12-weeks of surgery was conducted. The primary endpoint was the proportion of patients completing both VCB and ddTC.

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Purpose Of Review: To provide an updated overview of prognostic models in advanced cancer and highlight the role of prognostic calculators.

Recent Findings: In the advanced cancer setting, many important healthcare decisions are driven by a patient's prognosis. However, there is much uncertainty in formulating prognosis, particularly in the era of novel cancer therapeutics.

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Background: Gay, bisexual and other men who have sex with men (gbMSM) in Canada continue to experience high rates of incident HIV. Pre-exposure prophylaxis (PrEP, the regular use of anti-HIV medication) reduces HIV acquisition and could reduce incidence. However, there are too few physicians with expertise in HIV care to meet the projected demand for PrEP.

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Posterior cervical wiring has been used by spine surgeons in fixation procedures for patients with spinal instability. It is historically considered an effective method of treating cervical instability with a low risk of complications leading to neurological deterioration. We experienced a case of delayed neurological decline associated with myelopathy, lower extremity spasticity, and associated syringomyelia secondary to instrumentation failure and resultant sublaminar wire protrusion into the cervical spinal cord.

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Background: To maximize public health impact and cost-effectiveness, HIV pre-exposure prophylaxis (PrEP) must reach individuals at high HIV risk. Referrals for PrEP can be self- or provider-initiated, but there are several challenges to both. We assessed whether HIV risk differed by referral source among gay, bisexual and other men who have sex (gbMSM) screening for an HIV PrEP demonstration project.

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Vaginal drug delivery represents an attractive strategy for local and systemic delivery of drugs otherwise poorly absorbed after oral administration. The rather dense vascular network, mucus permeability and the physiological phenomenon of the uterine first-pass effect can all be exploited for therapeutic benefit. However, several physiological factors such as an acidic pH, constant secretion, and turnover of mucus as well as varying thickness of the vaginal epithelium can impact sustained drug delivery.

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Introduction: Identifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify "optimal" candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada.

Methods: Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify "optimal" candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP.

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