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Clearing the air: a review of the effects of air pollution on dialysis outcomes.
Spencer, A, Lavenburg, LM, Sanders, AP, Shah, AD
Current opinion in nephrology and hypertension. 2024;(2):192-202
Abstract
PURPOSE OF REVIEW An evolving body of literature indicates exposure to air pollutants is associated with adverse health outcomes in dialysis patients. As the prevalence of kidney disease increases, understanding the role of environmental agents on the health of dialysis patients is critical to reducing global morbidity and mortality. RECENT FINDINGS We identified 16 publications that investigated associations between pollutants including particulate matter (PM 2.5 and PM 10 ), carbon monoxide (CO), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and ozone (O 3 ) and health outcomes among dialysis patients. Eight studies examined the effects of particulate matter (PM) and four studies examined the effects CO exposure on dialysis patients. Exposure to PM was consistently associated with outcomes including all-cause mortality and a smaller body of literature suggested relationships with subclinical outcomes. Exposure to CO was associated with all-cause mortality, generalized inflammation, and uremic pruritus. An additional four studies examined multiple pollutant exposures including NO 2 , SO 2 , and O 3 and reported associations with all-cause mortality in dialysis patients. SUMMARY This review emphasized the nascent literature that demonstrates consistent relationships between air pollutant exposure and adverse outcomes among dialysis patients. Further research is needed to assess the impact of air pollutants, including how co-exposures will impact dialysis patient health.
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Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX.
Spencer, A, Moreau, P, Mateos, MV, Goldschmidt, H, Suzuki, K, Levin, MD, Sonneveld, P, Orlowski, RZ, Yoon, SS, Usmani, SZ, et al
Blood advances. 2024;(2):388-398
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Abstract
High-risk multiple myeloma (MM) is often defined based on cytogenetic abnormalities, but patients who relapse early after initial therapy are considered a functional high-risk group. In the phase 3 CASTOR and POLLUX studies, daratumumab plus bortezomib/dexamethasone (D-Vd) or lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS), regardless of cytogenetic risk, and achieved higher rates of complete response or better (≥CR) and minimal residual disease (MRD) negativity vs that with Vd/Rd alone in relapsed/refractory MM. Post hoc analyses of CASTOR and POLLUX evaluated patient subgroups with 1 prior line of therapy based on timing of progression/relapse (early or late) after initiation of first line of therapy. PFS consistently favored the daratumumab-containing regimens across subgroups using both a 24- and 18-month early-relapse cutoff. In the CASTOR/POLLUX pooled data set, daratumumab reduced the risk of disease progression or death by 65% (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.26-0.48; P < .0001) in the early-relapse (<24 months) subgroup and by 65% (HR, 0.35; 95% CI, 0.26-0.47; P < .0001) in the late-relapse (≥24 months) subgroup. OS also favored the daratumumab-containing regimens in both the early-relapse (HR, 0.62; 95% CI, 0.45-0.86; P = .0036) and late-relapse (HR, 0.67; 95% CI, 0.48-0.93; P = .0183) subgroups in the pooled population using a 24-month cutoff. Rates of ≥CR and MRD negativity (10-5) were higher with daratumumab vs control, regardless of progression/relapse timing. Although daratumumab is unable to fully overcome the adverse prognosis of early relapse, our results support the use of daratumumab for patients with 1 prior line of therapy, including for those who progress/relapse early after initial therapy and are considered to have functional high-risk MM. These trials were registered at www.clinicaltrials.gov as #NCT02136134 (CASTOR) and #NCT02076009 (POLLUX).
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Prevalence, trends and distribution of lifestyle cancer risk factors in Uganda: a 20-year systematic review.
Nakaganda, A, Mbarusha, I, Spencer, A, Patterson, L, Gemmell, I, Jones, A, Verma, A
BMC cancer. 2023;(1):311
Abstract
BACKGROUND Cancer is becoming an important public health problem in Uganda. Cancer control requires surveillance of lifestyle risk factors to inform targeted interventions. However, only one national Non-Communicable Disease (NCD) risk factor survey has been conducted in Uganda. This review assessed the prevalence, trends and distribution of lifestyle risk factors in Uganda. METHODS The review identified studies up to January 2019 by searching Medline, Embase, CINAL and Cochrane databases. Further literature was identified from relevant websites and journals; scanning reference lists of relevant articles; and citation searching using Google Scholar. To be eligible, studies had to have been conducted in Uganda, and report prevalence estimates for at least one lifestyle cancer risk factor. Narrative and systematic synthesis was used to analyse the data. RESULTS Twenty-four studies were included in the review. Overall, unhealthy diet (88%) was the most prevalent lifestyle risk factor for both males and females. This was followed by harmful use of alcohol (range of 14.3% to 26%) for men, and being overweight (range of 9% to 24%) for women. Tobacco use (range of 0.8% to 10.1%) and physical inactivity (range of 3.7% to 4.9%) were shown to be relatively less prevalent in Uganda. Tobacco use and harmful use of alcohol were more common in males and more prevalent in Northern region, while being overweight (BMI > 25 kg/m2) and physical inactivity were more common in females and more prevalent in Central region. Tobacco use was more prevalent among the rural populations compared to urban, while physical inactivity and being overweight were more common in urban than in rural settings. Tobacco use has decreased overtime, while being overweight increased in all regions and for both sexes. CONCLUSION There is limited data about lifestyle risk factors in Uganda. Apart from tobacco use, other lifestyle risk factors seem to be increasing and there is variation in the prevalence of lifestyle risk factors among the different populations in Uganda. Prevention of lifestyle cancer risk factors requires targeted interventions and a multi-sectoral approach. Most importantly, improving the availability, measurement and comparability of cancer risk factor data should be a top priority for future research in Uganda and other low-resource settings.
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The gut microbiome in konzo.
Bramble, MS, Vashist, N, Ko, A, Priya, S, Musasa, C, Mathieu, A, Spencer, A, Lupamba Kasendue, M, Mamona Dilufwasayo, P, Karume, K, et al
Nature communications. 2021;(1):5371
Abstract
Konzo, a distinct upper motor neuron disease associated with a cyanogenic diet and chronic malnutrition, predominately affects children and women of childbearing age in sub-Saharan Africa. While the exact biological mechanisms that cause this disease have largely remained elusive, host-genetics and environmental components such as the gut microbiome have been implicated. Using a large study population of 180 individuals from the Democratic Republic of the Congo, where konzo is most frequent, we investigate how the structure of the gut microbiome varied across geographical contexts, as well as provide the first insight into the gut flora of children affected with this debilitating disease using shotgun metagenomic sequencing. Our findings indicate that the gut microbiome structure is highly variable depending on region of sampling, but most interestingly, we identify unique enrichments of bacterial species and functional pathways that potentially modulate the susceptibility of konzo in prone regions of the Congo.
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Does L-Methylfolate Supplement Methylphenidate Pharmacotherapy in Attention-Deficit/Hyperactivity Disorder?: Evidence of Lack of Benefit From a Double-Blind, Placebo-Controlled, Randomized Clinical Trial.
Surman, C, Ceranoglu, A, Vaudreuil, C, Albright, B, Uchida, M, Yule, A, Spencer, A, Boland, H, Grossman, R, Rhodewalt, L, et al
Journal of clinical psychopharmacology. 2019;(1):28-38
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PURPOSE/BACKGROUND Interventions for attention-deficit/hyperactivity disorder (ADHD) may be inadequate for some patients. There is evidence that supplementation with L-methylfolate augments antidepressant agent effects and thus might also augment ADHD treatment effects by a common catecholaminergic mechanism. METHODS Forty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ADHD participated in a randomized, double-blind, placebo-controlled, 12-week trial of 15 mg of L-methylfolate in combination with osmotic-release oral system methylphenidate. Osmotic-release oral system methylphenidate was dose optimized over the first 6 weeks. We evaluated the effects on ADHD symptoms, self-report on the Behavior Rating Inventory of Executive Function of executive function, methylphenidate dosing, neuropsychological test measures, the Adult ADHD Self-report scale, emotional dysregulation, social adjustment, and work productivity, as well as moderating effects of body mass index, autoantibodies to folate receptors, and select genetic polymorphisms. RESULTS L-Methylfolate was well tolerated, with no significant effect over placebo except improvement from abnormal measures on the mean adaptive dimension of the ASR scale (χ = 4.36, P = 0.04). Methylphenidate dosing was significantly higher in individuals on L-methylfolate over time (χ = 7.35, P = 0.007). Exploratory analyses suggested that variation in a guanosine triphosphate cyclohydrolase gene predicted association with higher doses of methylphenidate (P < 0.001). CONCLUSIONS L-Methylfolate was associated with no change in efficacy on measures relevant to neuropsychiatric function in adults with ADHD, other than suggestion of reduced efficacy of methylphenidate. Further investigation would be required to confirm this effect and its mechanism and the genotype prediction of effects on dosing.
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Vitamin D Status and Gestational Diabetes: Effect of Smoking Status during Pregnancy.
Dodds, L, Woolcott, CG, Weiler, H, Spencer, A, Forest, JC, Armson, BA, Giguère, Y
Paediatric and perinatal epidemiology. 2016;(3):229-37
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BACKGROUND Vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D), has been shown in some studies to be inversely associated with gestational diabetes risk. Recently, it has been suggested that maternal smoking status may modify this relationship. We explored the association between 25(OH)D concentration and gestational diabetes and determined if there was an interaction between smoking and 25(OH)D. METHODS A nested case-control study was conducted in Halifax, Nova Scotia and Quebec City, Quebec. Women were recruited before 20 weeks gestation and 25(OH)D was measured. Cases were women who developed gestational diabetes and controls were frequency matched to cases on study site, gestational age at blood draw, and season and year of blood draw. Logistic regression models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI). Models were tested for multiplicative and additive interaction, which was estimated by relative excess risk due to interaction (RERI). RESULTS The study included 395 gestational diabetes cases and 1925 controls. Women who smoked during pregnancy and had 25(OH)D concentrations <30 nmol/L had an aOR = 3.73 [95% CI 1.95, 7.14] compared to non-smokers with 25(OH)D concentrations ≥50 nmol/L. Additive interaction was detected between smoking status and 25(OH)D [RERI = 2.44, 95% CI 0.03, 4.85]. CONCLUSION Our study supports the inverse association of vitamin D status with gestational diabetes risk, particularly among women who smoke during pregnancy. More research is needed to confirm this finding and, if confirmed, to determine the mechanism by which the combined effect of smoking and low vitamin D status increases the risk of developing gestational diabetes.
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High-dose cytarabine (24 g/m2) in combination with idarubicin (HiDAC-3) results in high first-cycle response with limited gastrointestinal toxicity in adult acute myeloid leukaemia.
Low, M, Lee, D, Coutsouvelis, J, Patil, S, Opat, S, Walker, P, Schwarer, A, Salem, H, Avery, S, Spencer, A, et al
Internal medicine journal. 2013;(3):294-7
Abstract
BACKGROUND/AIM: Although induction chemotherapy comprising high-dose cytarabine (HiDAC) in combination with idarubicin and etoposide or 'ICE' for adult acute myeloid leukaemia (AML) produces a complete remission rate of nearly 80%, gastrointestinal toxicity is significant. Omission of etoposide may produce similar clinical outcomes with potentially less gastrointestinal toxicity. METHODS Fifty-three consecutive patients aged 15-60 with newly diagnosed AML, receiving high-dose cytarabine induction at the Alfred Hospital, Melbourne, were retrospectively analysed. Regimens included HiDAC-3 (idarubicin 12 mg/m(2) day 1-3, cytarabine 3 gm/m(2) bd day 1,3,5,7) or ICE (idarubicin 9 mg/m(2) day 1-3, cytarabine 3 g/m(2) bd day 1,3,5,7, etoposide 75 mg/m(2) day 1-7). Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.03. RESULTS Thirty-one patients received HIDAC-3 and 22 patients received ICE induction. HiDAC-3 was better tolerated than ICE in terms of lower frequency of grade 3-4 nausea (0% vs 41%; P < 0.01), grade 3-4 diarrhoea (26% vs 55%; P = 0.05), lower rates of radiologically evident enterocolitis (6% vs 32%; P = 0.03) and less cumulative days of total parenteral nutrition use (1.2 vs 7.3 days; P < 0.01). Times to haematological recovery were similar between the two regimens. Thirty-day mortality was 0% for HiDAC-3 and 9% for ICE. Eighty-four per cent of HiDAC-3-treated patients achieved complete remission after the first cycle of therapy, compared with 77% with ICE. No differences in survival were evident between the two regimens. CONCLUSIONS HiDAC-3 is a clinically effective induction regimen for adult AML, producing a high rate of first-cycle complete remission with less treatment-related gastrointestinal toxicity than ICE.
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Hypertensive African American women and the DASH diet.
Spencer, A, Jablonski, R, Loeb, SJ
The Nurse practitioner. 2012;(2):41-6
Abstract
This integrative review identifies barriers to implementing the Dietary Approaches to Stop Hypertension (DASH) diet in hypertensive African American women. Databases were searched for original research published between 1999 and 2009. Barriers included clinicians' low adherence to nutritional counseling and patients' lack of knowledge regarding nutrition and the consequences of hypertension.
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Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma.
Henry, DH, Costa, L, Goldwasser, F, Hirsh, V, Hungria, V, Prausova, J, Scagliotti, GV, Sleeboom, H, Spencer, A, Vadhan-Raj, S, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011;(9):1125-32
Abstract
PURPOSE This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma. PATIENTS AND METHODS Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression). RESULTS Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading. CONCLUSION Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.
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The Logan Healthy Living Program: a cluster randomized trial of a telephone-delivered physical activity and dietary behavior intervention for primary care patients with type 2 diabetes or hypertension from a socially disadvantaged community--rationale, design and recruitment.
Eakin, EG, Reeves, MM, Lawler, SP, Oldenburg, B, Del Mar, C, Wilkie, K, Spencer, A, Battistutta, D, Graves, N
Contemporary clinical trials. 2008;(3):439-54
Abstract
BACKGROUND Physical activity and dietary behavior changes are important to both the primary prevention and secondary management of the majority of our most prevalent chronic conditions (i.e., cardiovascular disease, hypertension, type 2 diabetes, breast and colon cancer). With over 85% of Australian adults visiting a general practitioner each year, the general practice setting has enormous potential to facilitate wide scale delivery of health behaviour interventions. However, there are also many barriers to delivery in such settings, including lack of time, training, resources and remuneration. Thus there is an important need to evaluate other feasible and effective means of delivering evidence-based physical activity and dietary behaviour programs to patients in primary care, including telephone counseling interventions. METHODS Using a cluster randomized design with practice as the unit of randomization, this study evaluated a telephone-delivered intervention for physical activity and dietary change targeting patients with chronic conditions (type 2 diabetes or hypertension) recruited from primary care practices in a socially disadvantaged community in Queensland, Australia. Ten practices were randomly assigned to the telephone intervention or to usual care, and 434 patients were recruited. Patients in intervention practices received a workbook and 18 calls over 12 months. Assessment at baseline, 4-, 12- and 18-months allows for assessment of initial change and maintenance of primary outcomes (physical activity and dietary behavior change) and secondary outcomes (quality of life, cost-effectiveness, support for health behavior change). CONCLUSIONS This effectiveness trial adds to the currently limited number of telephone-delivered intervention studies targeting both physical activity and dietary change. It also addresses some of the shortcomings of previous trials by targeting patients from a disadvantaged community, and by including detailed reporting on participant representativeness, intervention implementation and cost-effectiveness, as well as an evaluation of maintenance of health behavior change.