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1.
J Hand Surg Am ; 48(7): 665-672, 2023 07.
Article in English | MEDLINE | ID: mdl-37256247

ABSTRACT

PURPOSE: Pediatric trigger finger (PTF) is an acquired condition that is uncommon and anatomically complex. Currently, the literature is characterized by a small number of retrospective case series with limited sample sizes. This investigation sought to evaluate the presentation, management, and treatment outcomes of PTF in a large, multicenter cohort. METHODS: A retrospective review of pediatric patients with a diagnosis of PTF between 2009 and 2020 was performed at three tertiary referral hospitals. Patient demographics, PTF characteristics, treatment strategies, and outcomes were abstracted from the electronic medical records. Patients and families also were contacted by telephone to assess the downstream persistence or recurrence of triggering symptoms. RESULTS: In total, 321 patients with 449 PTFs were included at a mean follow-up of 3.9 ± 4.0 years. There were approximately equal numbers of boys and girls, and the mean age of symptom onset was 5.4 ± 5.1 years. The middle (34.7%) and index (11.6%) fingers were the most and least commonly affected digits, respectively. Overall, PTFs managed operatively achieved significantly higher rates of complete resolution compared with PTFs managed nonsurgically (97.1% vs 30.0%). Seventy-five percent of PTFs that achieved complete resolution with nonsurgical management did so within 6 months, and approximately 90% did so within 12 months. Patients with multidigit involvement, higher Quinnell grade at presentation, or palpable nodularity were significantly more likely to undergo surgery. There was no significant difference in the rate of complete resolution between splinted versus not splinted PTFs or across operative techniques. CONCLUSIONS: Only 30% of the PTFs managed nonsurgically achieved complete resolution. Splinting did not improve resolution rates in children treated nonsurgically. In contrast, surgical intervention has a high likelihood of restoring motion and function of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Subject(s)
Trigger Finger Disorder , Male , Female , Humans , Child , Infant , Child, Preschool , Trigger Finger Disorder/therapy , Trigger Finger Disorder/surgery , Retrospective Studies , Fingers , Treatment Outcome , Splints
2.
N Engl J Med ; 381(7): 603-613, 2019 08 15.
Article in English | MEDLINE | ID: mdl-31180194

ABSTRACT

BACKGROUND: Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed. METHODS: We conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals. RESULTS: A total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed. CONCLUSIONS: Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , CD3 Complex/antagonists & inhibitors , Diabetes Mellitus, Type 1/prevention & control , Adolescent , Adult , Antibodies, Monoclonal, Humanized/adverse effects , Child , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Disease Progression , Double-Blind Method , Exanthema/chemically induced , Female , Glucose Tolerance Test , HLA-DR3 Antigen , HLA-DR4 Antigen , Humans , Lymphocyte Count , Lymphopenia/chemically induced , Male , Middle Aged , Proportional Hazards Models , T-Lymphocytes/immunology , Young Adult
3.
Curr Oncol Rep ; 24(12): 1829-1841, 2022 12.
Article in English | MEDLINE | ID: mdl-36197593

ABSTRACT

PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs) are a class of therapeutics that combine target-specific monoclonal antibodies with cytotoxic chemotherapy. Here, we describe the components of ADCs and review their promising activity, safety, and applicability in non-small cell lung cancer (NSCLC). RECENT FINDINGS: Technological advancements have reinvigorated ADCs as a viable treatment strategy in advanced solid tumors. Several target-specific ADCs have shown promise in treatment-refractory NSCLC, including agents targeting HER2, HER3, TROP2, CEACAM5, and MET, among others, with multiple confirmatory phase 3 trials ongoing. Critically, ADCs have demonstrated efficacy signals in both driver mutation-positive and mutation-negative advanced NSCLC, reinforcing their potential as an efficacious treatment strategy that transcends diverse tumor biology in advanced NSCLC. ADCs are a promising class of anti-cancer therapeutics that have significant potential in advanced NSCLC. Beyond confirmatory phase 3 trials, several questions remain including optimal agent sequencing, combinatorial methods, and unique toxicity management.


Subject(s)
Antineoplastic Agents, Immunological , Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Immunoconjugates , Lung Neoplasms , Humans , Immunoconjugates/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Antineoplastic Agents/therapeutic use , Lung Neoplasms/drug therapy , Antineoplastic Agents, Immunological/therapeutic use
4.
Diabetes Obes Metab ; 22(11): 2045-2054, 2020 11.
Article in English | MEDLINE | ID: mdl-32573927

ABSTRACT

AIMS: To test whether a long-acting GLP-1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function. METHODS: We performed a randomized placebo-controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C-peptide. Seventy-nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C-peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24 weeks. Participants were followed for another 6 months off study drug. RESULTS: At week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C-peptide. Those treated with exenatide ER lost weight at 12 and 24 weeks compared to those treated with placebo (P <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased. CONCLUSION: Treatment with exenatide ER may have short-term benefits in some individuals with T1D who are overweight or who have detectable levels of C-peptide, but short-term improvements were not sustained.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Diabetes Mellitus, Type 1/drug therapy , Exenatide , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Insulin , Venoms/therapeutic use
5.
Pain Med ; 21(7): 1377-1384, 2020 11 07.
Article in English | MEDLINE | ID: mdl-32022892

ABSTRACT

OBJECTIVE: To describe the efficacy of a comprehensive approach aimed at reducing opioid prescribing in an internal medicine resident clinic. DESIGN: Retrospective observational study. SETTING: Internal medicine primary care resident clinic at a large urban academic medical center. SUBJECTS: All patients receiving opioid prescriptions from the primary care clinic. METHODS: We reviewed pharmacy dispensing data for two hospital-affiliated pharmacies for resident primary care patients filling opioid prescriptions between July 2016 and July 2018. We instituted a comprehensive set of interventions that included resident education, limiting supervision of encounters for long-term opioid therapy (LTOT) to a fixed set of faculty champions, and providing alternate modalities for pain control. We calculated the change in number of opioid prescriptions dispensed, number of patients receiving opioid prescriptions, morphine milligram equivalents (MMEs) dispensed, and average per-patient daily MMEs dispensed. RESULTS: We observed an average monthly reduction of 2.44% (P < 0.001) in the number of prescriptions dispensed and a 1.83% (P < 0.001) monthly reduction in the number of patients receiving prescriptions. Over the two-year period, there was a 74.3% reduction in total MMEs prescribed and a 66.5% reduction in the average MMEs prescribed per patient. CONCLUSIONS: Our findings demonstrate a significant reduction in opioid prescribing after implementation of a comprehensive initiative. Although our study was observational in nature, we witnessed a nearly threefold decrease in opioid prescribing compared with national trends. Our results offer important insights for other primary care resident clinics hoping to engender safe prescribing practices and curb high-dose opioid prescribing.


Subject(s)
Analgesics, Opioid , Drug Prescriptions , Analgesics, Opioid/therapeutic use , Humans , Pain/drug therapy , Practice Patterns, Physicians' , Primary Health Care
6.
BMC Pediatr ; 19(1): 511, 2019 12 23.
Article in English | MEDLINE | ID: mdl-31870329

ABSTRACT

BACKGROUND: In developed economies, obesity prevalence is high within children from some culturally and linguistically diverse (CALD) backgrounds. This study aims to identify whether CALD groups in Victoria, Australia, are at increased risk of childhood overweight and obesity, and obesity-related dietary behaviours; compared to their non-CALD counterparts. METHODS: Objective anthropometric and self-report dietary behavioural data were collected from 2407 Grade 4 and 6 primary school children (aged 9-12 years). Children were categorised into CALD and non-CALD cultural groups according to the Australian Standard Classification of Languages. Overweight/obesity was defined according to the World Health Organization growth reference standards. Obesity-related dietary behaviour categories included excess consumption of takeaway foods, energy-dense, nutrient-poor snacks and sugar sweetened beverages. T-tests and chi-square tests were performed to identify differences in weight status and dietary behaviours between CALD and non-CALD children. Logistic regression analyses examined the relationship between CALD background, weight status and dietary behaviours. RESULTS: Middle-Eastern children had a higher overweight/obesity prevalence (53.0%) than non-CALD children (36.7%; p < 0.001). A higher proportion of Middle-Eastern children had excess consumption of takeaway foods (54.9%), energy-dense, nutrient-poor snacks (36.6%) and sugar sweetened beverages (35.4%) compared to non-CALD children (40.4, 27.0 and 25.0%, respectively; p < 0.05). Southeast Asian and African children were 1.58 (95% CI = [1.06, 2.35]) and 1.61 (95% CI = [1.17, 2.21]) times more likely, respectively, to consume takeaway foods at least once per week than non-CALD children. CONCLUSIONS: Disparities in overweight/obesity prevalence and obesity-related dietary behaviours among children in Victoria suggest the need for cultural-specific, tailored prevention and intervention strategies.


Subject(s)
Body Weight , Feeding Behavior , Pediatric Obesity/epidemiology , Child , Cross-Sectional Studies , Cultural Characteristics , Female , Humans , Language , Male , Risk Assessment , Victoria
7.
J Res Adolesc ; 29(3): 710-723, 2019 09.
Article in English | MEDLINE | ID: mdl-29770516

ABSTRACT

The potential for peers to influence obesity risk behavior increases in adolescence, yet there are knowledge gaps of how behaviors are modified in response to peers over time. This study examined how personal friendship network characteristics were associated with obesity-related behaviors from late childhood to early adolescence. Two waves of friendship, physical activity, screen time, and dietary recall data were collected from 11- to 13-year-old students (99% retention) in Australia (n = 308) over a five- to eight-month period. Regression models identified friendship network characteristics that predicted later health behaviors which varied by gender and behavior type, such as the number of friends positively associated with physical activity intensity (males) and screen time (females). The need for considering context to influence behavior change is discussed.


Subject(s)
Exercise/psychology , Friends/psychology , Health Behavior/physiology , Obesity/psychology , Adolescent , Australia/epidemiology , Child , Cross-Sectional Studies , Diet Records , Female , Humans , Longitudinal Studies , Male , Obesity/epidemiology , Peer Group , Risk-Taking
8.
Health Promot J Austr ; 30(1): 28-36, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29729211

ABSTRACT

ISSUE ADDRESSED: Schools are a target for childhood obesity prevention strategies, yet intervention effectiveness may be hindered by school community perceptions (staff and students) and readiness to address the problem. We firstly describe students' perception of their own weight status. Secondly, we describe school staff perceptions and preparedness to address childhood obesity in their school. METHODS: Measured and self-report weight status were collected simultaneously from 11- to 14-year-old students (N = 339/733; RR 46%) recruited from 42 schools in Victoria, Australia. Student objective weight status was compared to self-report. School community readiness to address childhood obesity data was collected from staff (N = 114) at all participating schools. School readiness survey data were scored and descriptive analyses conducted for further insight of derived readiness scores. RESULTS: Using objective assessment, 18% (n = 62) of students were obese, but only 4% (n = 12) accurately identified themselves as obese. School communities were concerned about the problem of childhood obesity in general, yet were assessed at low stages of readiness to take action within their community. Descriptive data identified a strong focus on promoting healthy eating and physical activity through education. Further efforts to target childhood obesity appeared to be hindered by limited support, resources and engagement with the broader community. CONCLUSION: Perceptions of childhood obesity prevalence, low stages of readiness and limited school capacity may hinder prevention strategies. SO WHAT?: Perceptions of what is normal weight may have implications for prevention. Efforts must be informed by accurate weight data and require a broader community approach beyond the school environment.


Subject(s)
Attitude to Health , Pediatric Obesity/psychology , School Teachers/psychology , Social Perception , Students/psychology , Adolescent , Body Weight , Child , Female , Humans , Male , Pediatric Obesity/epidemiology , Schools , Self Report , Surveys and Questionnaires , Victoria/epidemiology
9.
Diabetologia ; 61(1): 84-92, 2018 01.
Article in English | MEDLINE | ID: mdl-28956083

ABSTRACT

AIMS/HYPOTHESIS: We aimed to examine: (1) whether specific glucose-response curve shapes during OGTTs are predictive of type 1 diabetes development; and (2) the extent to which the glucose-response curve is influenced by insulin secretion. METHODS: Autoantibody-positive relatives of people with type 1 diabetes whose baseline OGTT met the definition of a monophasic or biphasic glucose-response curve were followed for the development of type 1 diabetes (n = 2627). A monophasic curve was defined as an increase in OGTT glucose between 30 and 90 min followed by a decline of ≥ 0.25 mmol/l between 90 and 120 min. A biphasic response curve was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 0.25 mmol/l. Associations of type 1 diabetes risk with glucose curve shapes were examined using cumulative incidence curve comparisons and proportional hazards regression. C-peptide responses were compared with and without adjustments for potential confounders. RESULTS: The majority of participants had a monophasic curve at baseline (n = 1732 [66%] vs n = 895 [34%]). The biphasic group had a lower cumulative incidence of type 1 diabetes (p < 0.001), which persisted after adjustments for age, sex, BMI z score and number of autoantibodies (p < 0.001). Among the monophasic group, the risk of type 1 diabetes was greater for those with a glucose peak at 90 min than for those with a peak at 30 min; the difference persisted after adjustments (p < 0.001). Compared with the biphasic group, the monophasic group had a lower early C-peptide (30-0 min) response, a lower C-peptide index (30-0 min C-peptide/30-0 min glucose), as well as a greater 2 h C-peptide level (p < 0.001 for all). CONCLUSIONS/INTERPRETATION: Those with biphasic glucose curves have a lower risk of progression to type 1 diabetes than those with monophasic curves, and the risk among the monophasic group is increased when the glucose peak occurs at 90 min than at 30 min. Differences in glucose curve shapes between the monophasic and biphasic groups appear to be related to C-peptide responses.


Subject(s)
C-Peptide/metabolism , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/metabolism , Glucose Tolerance Test/methods , Adult , Blood Glucose/metabolism , Female , Humans , Insulin/metabolism , Male , Middle Aged
10.
J Sports Sci ; 36(14): 1614-1622, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29157151

ABSTRACT

Participation in organized sports is promoted as a means of increasing physical activity levels and reducing chronic disease risk in adults. Hard martial arts practice (i.e. using body contact techniques), has gained in popularity over time. This review explores the evidence for health benefits of "hard" martial arts practice within the adult population. A systematic electronic database search was conducted, and quality assessments applied the Effective Public Health Practice Project tool. Twenty-eight studies met the inclusion criteria, examining balance, cognitive function, muscular skeletal status, psychological, cardiovascular fitness, and metabolic effects. The majority of studies reported positive effects resulting from hard martial arts practice, showing some improvement and maintenance of balance, cognitive function and psychological health. Benefits may be obtained regardless of the age of practice commencement. However, quality of the evidence is affected by methodological weaknesses across the studies. "Hard" martial arts seem to have potential to improve balance and cognitive functions that decline with age, which can lead to poorer health outcomes among the elderly (e.g. cognitive decline, falls and fractures). Benefits should be further investigated with improved intervention studies, representative samples and longer follow-up periods in order to establish associations with morbidity and mortality in the long term.


Subject(s)
Martial Arts/physiology , Martial Arts/psychology , Adult , Cardiorespiratory Fitness/physiology , Cognition/physiology , Humans , Martial Arts/injuries , Muscle Strength/physiology , Muscle, Skeletal/physiology , Postural Balance/physiology
12.
J Interprof Care ; 30(4): 466-74, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27268513

ABSTRACT

Interprofessional (IP) care is critical for effective pain management, but evidence is lacking about the best way to teach pain management skills to medical and nursing students using IP strategies. In 2013 and 2014, 307 medical and 169 nursing students participated in an IP case-based pain management workshop. The aims of this study were to determine (1) if students who participate in IP case-based learning groups will have improved pain management skills compared to students who participate in uniprofessional case-based learning groups, and (2) if students mentored by faculty with IP training will have improved pain management skills compared to students who are not mentored by IP-trained faculty. Student learning was assessed and compared using scored checklists for each group's pain management plans. Findings show that IP mentorship and IP group participation improved medical students' pain management skills but did not have the same effect on nursing student performance. Continued work is needed to develop, refine, and integrate innovative and tailored IP strategies into the curricula of medical and nursing schools to advance the pain management competencies of students before they enter clinical practice.


Subject(s)
Curriculum , Interdisciplinary Communication , Pain Management , Students, Medical , Students, Nursing , Checklist , Cross-Sectional Studies , Female , Humans , Male , Self Report , Young Adult
13.
Int J Behav Nutr Phys Act ; 12: 59, 2015 May 08.
Article in English | MEDLINE | ID: mdl-25952318

ABSTRACT

BACKGROUND: There is little empirical evidence of the impact of transition from primary to secondary school on obesity-related risk behaviour. The purpose of this study was to examine the effect of a change of school system on physical activity (PA) and sedentary behaviour in pre-early adolescents. METHODS: Fifteen schools in Victoria, Australia were recruited at random from the bottom two strata of a five level socio-economic scale. In nine schools, students in year 6 primary school transitioned to a different school for year 7 secondary school, while in six schools (combined primary-secondary), students remained in the same school environment from year 6 to year 7. Time 1 (T1) measures were collected from students (N=245) in year 6 (age 11-13). Time 2 (T2) data were collected from 243 (99%) of the original student cohort when in year 7. PA and sedentary behaviour data were collected objectively (via ActiGraph accelerometer) and subjectively (via child self-report recall questionnaire). School environment data were collected via school staff survey. Change of behaviour analyses were conducted longitudinally i) for all students and ii) by change/no change of school. Mixed model regression analysis tested for behavioural interaction effects of changing/not changing school. RESULTS: Sixty-three percent (N=152) changed schools from T1 to T2. Across all students we observed declines in average daily moderate to vigorous physical activity (MVPA) (-4 min) and light PA (-23 min), and increases in average daily sedentary behaviour (16 min), weekday leisure screen time (17 min) and weekday homework screen time (25 min), all P<0.05. Compared to students who remained in the same school environment, students who changed school reported a greater reduction in PA intensity at recess and lunch, less likelihood to cycle to/from school, greater increase in weekday (41 mins) and weekend (45 mins) leisure screen time (P<0.05) and greater encouragement to participate in sport. School staff surveys identified that sport participation encouragement was greater in primary and combined primary-secondary than secondary schools (P<0.05). CONCLUSION: Transitioning from primary to secondary school negatively impacts on children's PA and sedentary behaviour, and has further compounding effects on behaviour type by changing school environments.


Subject(s)
Environment , Motor Activity , Schools , Sedentary Behavior , Students , Adolescent , Australia , Child , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Socioeconomic Factors
14.
Prev Chronic Dis ; 12: E145, 2015 Sep 10.
Article in English | MEDLINE | ID: mdl-26355826

ABSTRACT

INTRODUCTION: Environments that facilitate energy-dense, nutrient-poor diets are associated with childhood obesity. We examined the effect of a change of school environment on the prevalence of obesity and related dietary behavior in early adolescence. METHODS: Fifteen schools in Victoria, Australia, were recruited at random from the bottom 2 strata of a 5-level socioeconomic scale. In 9 schools, students in grade 6 primary school transitioned to different schools for grade 7 secondary school, whereas in 6 schools, students remained in the same school from grade 6 to grade 7. Time 1 measures were collected from students (N = 245) in grade 6 (aged 11-13 y). Time 2 data were collected from 243 (99%) of the original cohort in grade 7. Data collected were dietary recall self-reported by students via questionnaire, measured height and weight of students, and aspects of the school food environment via school staff survey. Comparative and mixed model regression analyses were conducted. RESULTS: Of 243 students, 63% (n = 152) changed schools from time 1 to time 2, with no significant difference in weight status. Students who changed schools reported an increase in purchases of after-school snack food, greater sweetened beverage intake, fewer fruit-and-vegetable classroom breaks, and less encouragement for healthy eating compared with students who remained in the same school. School staff surveys showed that more primary than secondary schools had written healthy canteen policies and fewer days of canteen or food services operation. CONCLUSION: A change of school environment has negative effects on children's obesity-related dietary behavior. Consistent policy is needed across school types to support healthy eating in school environments.


Subject(s)
Diet/psychology , Feeding Behavior/psychology , Obesity/epidemiology , School Health Services/standards , Schools/statistics & numerical data , Adolescent , Adolescent Behavior , Anthropometry , Child , Cohort Studies , Diet/adverse effects , Diet/economics , Energy Intake , Female , Food Dispensers, Automatic/statistics & numerical data , Fruit , Health Knowledge, Attitudes, Practice , Humans , Linear Models , Longitudinal Studies , Male , Overweight/epidemiology , Residence Characteristics/statistics & numerical data , Self Report , Snacks/psychology , Social Class , Students/psychology , Students/statistics & numerical data , Surveys and Questionnaires , Victoria
15.
Lancet ; 381(9881): 1905-15, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-23562090

ABSTRACT

BACKGROUND: Innate immunity contributes to the pathogenesis of autoimmune diseases, such as type 1 diabetes, but until now no randomised, controlled trials of blockade of the key innate immune mediator interleukin-1 have been done. We aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1 antibody, or anakinra, a human interleukin-1 receptor antagonist, improved ß-cell function in recent-onset type 1 diabetes. METHODS: We did two randomised, placebo-controlled trials in two groups of patients with recent-onset type 1 diabetes and mixed-meal-tolerance-test-stimulated C peptide of at least 0·2 nM. Patients in the canakinumab trial were aged 6-45 years and those in the anakinra trial were aged 18-35 years. Patients in the canakinumab trial were enrolled at 12 sites in the USA and Canada and those in the anakinra trial were enrolled at 14 sites across Europe. Participants were randomly assigned by computer-generated blocked randomisation to subcutaneous injection of either 2 mg/kg (maximum 300 mg) canakinumab or placebo monthly for 12 months or 100 mg anakinra or placebo daily for 9 months. Participants and carers were masked to treatment assignment. The primary endpoint was baseline-adjusted 2-h area under curve C-peptide response to the mixed meal tolerance test at 12 months (canakinumab trial) and 9 months (anakinra trial). Analyses were by intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00947427 and NCT00711503, and EudraCT number 2007-007146-34. FINDINGS: Patients were enrolled in the canakinumab trial between Nov 12, 2010, and April 11, 2011, and in the anakinra trial between Jan 26, 2009, and May 25, 2011. 69 patients were randomly assigned to canakinumab (n=47) or placebo (n=22) monthly for 12 months and 69 were randomly assigned to anakinra (n=35) or placebo (n=34) daily for 9 months. No interim analyses were done. 45 canakinumab-treated and 21 placebo-treated patients in the canakinumab trial and 25 anakinra-treated and 26 placebo-treated patients in the anakinra trial were included in the primary analyses. The difference in C peptide area under curve between the canakinumab and placebo groups at 12 months was 0·01 nmol/L (95% CI -0·11 to 0·14; p=0·86), and between the anakinra and the placebo groups at 9 months was 0·02 nmol/L (-0·09 to 0·15; p=0·71). The number and severity of adverse events did not differ between groups in the canakinumab trial. In the anakinra trial, patients in the anakinra group had significantly higher grades of adverse events than the placebo group (p=0·018), which was mainly because of a higher number of injection site reactions in the anakinra group. INTERPRETATION: Canakinumab and anakinra were safe but were not effective as single immunomodulatory drugs in recent-onset type 1 diabetes. Interleukin-1 blockade might be more effective in combination with treatments that target adaptive immunity in organ-specific autoimmune disorders. FUNDING: National Institutes of Health and Juvenile Diabetes Research Foundation.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/therapeutic use , Immunologic Factors/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Adolescent , Adult , Analysis of Variance , Antibodies, Monoclonal, Humanized , C-Peptide/drug effects , Child , Double-Blind Method , Female , Humans , Insulin-Secreting Cells/drug effects , Interleukin-1/antagonists & inhibitors , Male , Treatment Outcome , Young Adult
16.
J Obstet Gynaecol Can ; 36(2): 141-145, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24518913

ABSTRACT

BACKGROUND: Endocervicosis, endosalpingiosis, endometriosis, and adenomyosis represent choristomas of Mullerian origin and are referred to as mullerianosis. These conditions frequently coexist, and they may present with pelvic pain, mass lesions, and/or infertility. Clinically, they are indistinguishable from one another, and histologically their epithelium is that of the endocervix, endosalpinx, or endometrium. Endocervicosis can be found in the urinary tract, frequently presenting as a bladder lesion or bladder dysfunction. CASE: We report here a case of bladder endocervicosis in a woman with extensive endometriosis and a bladder tumour who presented with chronic pelvic pain and infertility. Pelvic endometriosis was excised and vaporized with the CO2 laser, and the bladder lesion was excised in a combined transurethral and laparoscopic approach using the CO2 laser and robotic monopolar electrosurgical scissors. The cystotomy was then repaired using the robot, and the patient had an uneventful recovery with good clinical outcomes including spontaneous conception. CONCLUSION: Endocervicosis of the urinary bladder is a rare Mullerian choristoma. Symptomatic lesions can be removed surgically by various surgical techniques, and a collaborative team-based approach is in the patient's best interest.


Contexte : L'endocervicose, l'endosalpingiose, l'endométriose et l'adénomyose constituent des choristomes d'origine müllérienne et sont connues sous le nom de mullérianose. Ces pathologies coexistent fréquemment et peuvent donner lieu à de la douleur pelvienne, à des lésions de masse et/ou à une infertilité. Sur le plan clinique, elles ne peuvent être distinguées l'une de l'autre et, sur le plan histologique, leur épithélium est celui de l'endocol, de l'endosalpinx ou de l'endomètre. La présence d'une endocervicose peut être constatée dans les voies urinaires et prend fréquemment la forme d'une lésion ou d'une dysfonction vésicale. Cas : Nous signalons ici un cas d'endocervicose vésicale chez une femme qui présentait une endométriose étendue et une tumeur vésicale, et qui connaissait des douleurs pelviennes chroniques et une infertilité. L'endométriose pelvienne a été excisée et vaporisée au moyen d'un laser CO2, et la lésion vésicale a été excisée au moyen d'une approche combinée transurétrale et laparoscopique faisant appel au laser CO2 et à des ciseaux électrochirurgicaux monopolaires robotisés. La cystotomie a par la suite été réparée au moyen du robot et la patiente a connu une récupération sans incidents s'accompagnant de bonnes issues cliniques (y compris une conception spontanée). Conclusion : L'endocervicose de la vessie constitue un rare choristome d'origine müllérienne. Les lésions symptomatiques peuvent être retirées au moyen de chirurgies faisant appel à diverses techniques; le recours à une approche d'équipe concertée constitue la mesure qui est la plus favorable pour la patiente.


Subject(s)
Cervix Uteri , Choristoma/surgery , Cystectomy/methods , Laparoscopy , Robotics , Urinary Bladder Diseases/surgery , Adult , Choristoma/complications , Choristoma/diagnosis , Electrosurgery , Endometriosis/complications , Endometriosis/surgery , Female , Humans , Infertility, Female/etiology , Infertility, Female/therapy , Laser Therapy , Mullerian Ducts , Pelvic Pain , Urinary Bladder Diseases/diagnosis
17.
Biomedicines ; 12(5)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38790937

ABSTRACT

The management of elderly patients diagnosed with acute myelogenous leukemia (AML) is complicated by high relapse risk and comorbidities that often preclude access to allogeneic hematopoietic cellular transplantation (allo-HCT). In recent years, fast-paced FDA drug approval has reshaped the therapeutic landscape, with modest, albeit promising improvement in survival. Still, AML outcomes in elderly patients remain unacceptably unfavorable highlighting the need for better understanding of disease biology and tailored strategies. In this review, we discuss recent modifications suggested by European Leukemia Network 2022 (ELN-2022) risk stratification and review recent aging cell biology advances with the discussion of four AML cases. While an older age, >60 years, does not constitute an absolute contraindication for allo-HCT, the careful patient selection based on a detailed and multidisciplinary risk stratification cannot be overemphasized.

18.
Cancers (Basel) ; 16(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38611091

ABSTRACT

Precision immuno-oncology involves the development of personalized cancer treatments that are influenced by the unique nature of an individual's DNA, immune cells, and their tumor's molecular characterization. Biological sex influences immunity; females typically mount stronger innate and adaptive immune responses than males. Though more research is warranted, we continue to observe an enhanced benefit for females with lung cancer when treated with combination chemoimmunotherapy in contrast to the preferred approach of utilizing immunotherapy alone in men. Despite the observed sex differences in response to treatments, women remain underrepresented in oncology clinical trials, largely as a result of gender-biased misconceptions. Such exclusion has resulted in the development of less efficacious treatment guidelines and clinical recommendations and has created a knowledge gap in regard to immunotherapy-related survivorship issues such as fertility. To develop a more precise approach to care and overcome the exclusion of women from clinical trials, flexible trial schedules, multilingual communication strategies, financial, and transportation assistance for participants should be adopted. The impact of intersectionality and other determinants of health that affect the diagnosis, treatment, and outcomes in women must also be considered in order to develop a comprehensive understanding of the unique impact of immunotherapy in all women with lung cancer.

19.
J Obstet Gynaecol Can ; 35(2): 164-167, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23470067

ABSTRACT

BACKGROUND: Retroperitoneal cysts can be asymptomatic or can present with vague symptoms such as abdominal pain or distension. Their clinical implications vary significantly. CASE: A 45-year-old woman, gravida 2, para 2, presented with vague, non-specific pelvic symptomatology. Imaging indicated a right-sided pelvic cyst 5 cm in diameter. At laparoscopy a retroperitoneal cyst was identified, with a normal pelvis and intra-abdominal organs. No attempt was made at laparoscopy to drain, biopsy, or excise the cyst. CT-guided biopsy of the cyst was performed and small intestine mucosa was identified with goblet cells and smooth muscle. Repeat biopsy confirmed areas of tissue necrosis and small intestine mucosa, with additional tissue containing respiratory epithelium. Following laparotomy and excision of the cyst, the final pathologic diagnosis was benign epithelial cyst consistent with a duplication or hindgut cyst. CONCLUSION: Although most retroperitoneal cysts are benign, surgical excision is required to rule out malignancy definitively.


Subject(s)
Cysts/diagnosis , Cysts/surgery , Retroperitoneal Space , Biopsy , Cysts/pathology , Diagnosis, Differential , Female , Humans , Laparoscopy , Laparotomy , Middle Aged
20.
JTO Clin Res Rep ; 4(6): 100521, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37251503

ABSTRACT

We report a case of a patient with Li Fraumeni Syndrome (LFS) who developed synchronous EGFR exon deletion 19 and EGFR exon 20 insertion NSCLC and characterize the diagnostic and therapeutic challenges in managing her care. Osimertinib was effective in the EGFR deletion 19 population but did not garner a response in the EGFR exon 20 insertion population, which was treated definitively with surgical resection. At the time of oligoprogression, she underwent surgical resection, and radiation therapy was minimized. The biologic link between LFS and EGFR mutation remains unclear, and using larger, real-world cohorts could help to clarify the relationship between LFS and EGFR-mutant NSCLC.

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