DAVID WILLIAMS - Academia.edu (original) (raw)

Papers by DAVID WILLIAMS

Journal of Physical Oceanography, Apr 1, 2021

Meteotsunamis are shallow-water waves that, despite often being small (;0.3 m), can cause damage,... more Meteotsunamis are shallow-water waves that, despite often being small (;0.3 m), can cause damage, injuries, and fatalities due to relatively strong currents (.1 m s 21). Previous case studies, modeling, and localized climatologies have indicated that dangerous meteotsunamis can occur across northwest Europe. Using 71 tide gauges across northwest Europe between 2010 and 2017, a regional climatology was made to understand the typical sizes, times, and atmospheric systems that generate meteotsunamis. A total of 349 meteotsunamis (54.0 meteotsunamis per year) were identified with 0.27-0.40-m median wave heights. The largest waves (;1 m high) were measured in France and the Republic of Ireland. Most meteotsunamis were identified in winter (43%-59%), and the fewest identified meteotsunamis occurred in either spring or summer (0%-15%). There was a weak diurnal signal, with most meteotsunami identifications between 1200 and 1859 UTC (30%) and the fewest between 0000 and 0659 UTC (23%). Radar-derived precipitation was used to identify and classify the morphologies of mesoscale precipitating weather systems occurring within 6 h of each meteotsunami. Most mesoscale atmospheric systems were quasi-linear systems (46%) or open-cellular convection (33%), with some nonlinear clusters (17%) and a few isolated cells (4%). These systems occurred under westerly geostrophic flow, with Proudman resonance possible in 43 out of 45 selected meteotsunamis. Because most meteotsunamis occur on cold winter days, with precipitation, and in large tides, wintertime meteotsunamis may be missed by eyewitnesses, helping to explain why previous observationally based case studies of meteotsunamis are documented predominantly in summer.

Journal of Physical Oceanography, 2021

Meteotsunamis are shallow-water waves that, despite often being small (~0.3 m), can cause damage,... more Meteotsunamis are shallow-water waves that, despite often being small (~0.3 m), can cause damage, injuries, and fatalities due to relatively strong currents (>1 m s−1). Previous case studies, modeling, and localized climatologies have indicated that dangerous meteotsunamis can occur across northwest Europe. Using 71 tide gauges across northwest Europe between 2010 and 2017, a regional climatology was made to understand the typical sizes, times, and atmospheric systems that generate meteotsunamis. A total of 349 meteotsunamis (54.0 meteotsunamis per year) were identified with 0.27–0.40-m median wave heights. The largest waves (~1 m high) were measured in France and the Republic of Ireland. Most meteotsunamis were identified in winter (43%–59%), and the fewest identified meteotsunamis occurred in either spring or summer (0%–15%). There was a weak diurnal signal, with most meteotsunami identifications between 1200 and 1859 UTC (30%) and the fewest between 0000 and 0659 UTC (23%). Ra...

Natural Hazards, 2020

Proudman resonance is a primary amplification mechanism for meteotsunamis, which are shallow-wate... more Proudman resonance is a primary amplification mechanism for meteotsunamis, which are shallow-water waves generated by atmospheric forcings. The effect of tides, sloping bathymetry and the speed, amplitude and aspect ratio of the atmospheric forcing on Proudman resonant wave growth are investigated using analytical approximations and numerical models. With tides included, maximum wave growth through Proudman resonance occurred when the atmospheric-forcing speed matched the tidal-wave speed. Growth greater than Proudman resonance occurred with a positive tidal elevation together with a tidal current in the opposite direction to wave propagation, due to linear growth combined with further amplification from wave-flux conservation. Near-Proudman resonant growth occurred when the forced-wave speed or free-wave speed varied by either a small amount, or varied rapidly, around a speed appropriate for Proudman resonance. For a forcing moving at Proudman resonant speed, resultant wave growth ...

The American journal of occupational therapy : official publication of the American Occupational Therapy Association

This study assessed the feasibility and preliminary efficacy of an online-assisted, occupational ... more This study assessed the feasibility and preliminary efficacy of an online-assisted, occupational therapist-delivered, cognitive-behavioral therapy intervention to promote physical function in patients with knee osteoarthritis (KOA). Fifty-seven participants with KOA were randomized 2:1 to the Engage program (eight clinic-based sessions supported by online modules) or usual care. Using analysis of covariance, we estimated Engage's effect on physical function (Western Ontario and McMaster Universities Osteoarthritis Index's Physical Function subscale [WOMAC-PF]) at 6 mo. Data were analyzed on 46 completers. Engage was associated with a small effect (η² = 0.01) on the WOMAC-PF. More Engage participants than controls reported much or very much improvement (45% vs. 13%; p = .03). Satisfaction was high, and 30 of 31 participants attended six sessions or more. An online-supported cognitive-behavioral program for people with KOA delivered by occupational therapists is feasible and m...

Annals of behavioral medicine : a publication of the Society of Behavioral Medicine, Jan 13, 2018

Adverse Childhood Experiences (ACEs) such as sexual and physical violence, serious illness, and b... more Adverse Childhood Experiences (ACEs) such as sexual and physical violence, serious illness, and bereavement have been linked to number of chronic pain conditions in adulthood, and specifically to urologic chronic pelvic pain syndrome (UCPPS). We sought to characterize the prevalence of ACEs in UCPPS using a large well-characterized cohort in comparison with a group of healthy controls. We also sought to determine the association of ACE severity with psychological factors known to impact pain and to determine whether ACEs are associated with patterns of improvement or worsening of symptom over a year of naturalistic observation. For longitudinal analyses we used functional clusters identifying broad classes of (a) improved, (b) worsened, and (c) stable groups for genitourinary pain and urinary symptoms. We employed a mediation/path analysis framework to determine whether ACEs influenced 1 year outcomes directly, or indirectly through worse perceptions of physical well-being. ACE seve...

The Journal of pediatrics, Jan 25, 2018

To evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of... more To evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and pediatric enthesitis-related arthritis), psoriasis, and Crohn's disease. This analysis included data from 7 global, randomized, and open-label AbbVie-sponsored clinical trials of adalimumab and their open-label extensions conducted between September 2002 and December 31, 2015 (cutoff date for ongoing studies). Patients who received ≥1 dose of adalimumab subcutaneously were included. Adverse events that occurred after the first dose of adalimumab and up to 70 days (5 half-lives) after the last dose were reported and events per 100 patient-years were calculated. The analysis included 577 pediatric patients, representing 1440.7 patient-years of adalimumab exposure. Across indications, the most commonly reported adverse events (events/100 patient-years) were upper respiratory tract infections (24.3), nasophar...

Pain, Jan 28, 2018

Chronic Overlapping Pain Conditions (COPCs) are characterized by aberrant central nervous system ... more Chronic Overlapping Pain Conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This 'centralized pain' phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here we used three cohorts, including patients with Urologic Chronic Pelvic Pain Syndrome (UCPPS), a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified two general factors in all three cohorts, one characterized by a broad increased sensitivity to internal somatic sensations and environmental stimuli, and diffuse pain, termed Generaliz...

Oncology nursing forum, Jan 2, 2018

To explore associations between quantitative sensory testing (QST) and pretreatment pain, physica... more To explore associations between quantitative sensory testing (QST) and pretreatment pain, physical, and psychological characteristics in women with breast cancer. 41 women with treatment-naive stage 0-III breast cancer at the University of Michigan Comprehensive Cancer Center in Ann Arbor. Participants completed self-report surveys and QST within the month before breast surgery. Pressure pain thresholds (PPTs) were measured bilaterally at each trapezius with a manual QST algometer. PPT values were split, yielding low, moderate, and high pain sensitivity subgroups. Subgroup self-reported characteristics were compared using Spearman's correlation, chi-square, and one-way analysis of variance. Lower PPT (higher sensitivity) was associated with higher levels of pain interference and maladaptive pain cognitions. The high-sensitivity group reported higher pain severities, interference, and catastrophizing and lower belief in internal locus of pain control than the low-sensitivity grou...

The journal of pain : official journal of the American Pain Society, Dec 30, 2016

Somatic awareness (SA) refers to heightened sensitivity to a variety of physical sensations and s... more Somatic awareness (SA) refers to heightened sensitivity to a variety of physical sensations and symptoms. Few attempts have been made to dissociate the relationship of SA and affective symptoms with pain outcomes. We used a validated measure of mood and anxiety symptoms that includes questions related to SA to predict the number of tender points found on physical examination in a large cross-sectional community sample (the Midlife in the United States [MIDUS] Biomarker study). General distress, positive affect, and SA, which were all significantly associated with tender point number in bivariate analyses, were used as predictors of the number of tender points in a multivariate negative binomial regression model. In this model a greater number of tender points was associated with higher levels of SA (p = .02) but not general distress (p = .13) or positive affect (p = .50). Follow-up mediation analyses indicated that the relationship between general distress and tender points was part...

Therapeutic advances in drug safety, 2011

A number of drug classes are licensed for the treatment of osteoporosis including bisphosphonates... more A number of drug classes are licensed for the treatment of osteoporosis including bisphosphonates, recombinant human parathyroid hormone (PTH), strontium, hormone replacement therapy (HRT), selective oestrogen receptor modulators (SERMS) and denosumab. This review discusses the safety of osteoporosis treatments and their efficacies. Recent concerns about the safety of calcium and high-dose vitamin D are discussed. Bisphosphonates have substantial postmarketing experience and a clearer picture of safety issues is emerging. Along with the well recognized effects on the gastrointestinal tract and kidney function, recently described adverse effects such as osteonecrosis of the jaw, oesophageal cancer, atrial fibrillation, subtrochanteric femur fractures and ocular complications of bisphosphonate therapy are discussed. Therapy with PTH is limited to two years' duration because of the development of osteogenic sarcomas in animal studies, which appeared related to dose, duration and ti...

Journal of Pediatric Hematology/Oncology, 2002

The Journal of Pain, 2014

Aromatase inhibitors (AI), which are used to treat breast cancer, inhibit estrogen production in ... more Aromatase inhibitors (AI), which are used to treat breast cancer, inhibit estrogen production in postmenopausal women. AI-associated musculoskeletal symptoms (AIMSS) occur in approximately half of treated women, and lead to treatment discontinuation in 20-30%. The etiology may be due in part to estrogen deprivation. In premenopausal women, lower estrogen levels have been associated with increased pain, as well as with impairment of descending pain inhibitory pathways, which may be a risk factor for developing chronic pain. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AIMSS. Fifty postmenopausal breast cancer patients underwent pressure pain testing and conditioned pain modulation (CPM) assessment prior to AI initiation and after 3 and 6 months. At baseline, 26 of 40 (65%) assessed patients demonstrated impaired CPM, which was greater in those who had previously received chemotherapy (p=0.006). No statistically significant change in pressure pain threshold or CPM was identified following estrogen deprivation. In

Circulation, 2004

Background— Noninvasive measures of arterial compliance may be useful for the detection of subcli... more Background— Noninvasive measures of arterial compliance may be useful for the detection of subclinical atherosclerosis. Methods and Results— Measures of calf and thigh arterial compliance (MaxV50) were recorded in 267 subjects who also underwent MRI of the distal aorta to quantify distal aorta atherosclerosis. The average of calf and thigh MaxV50 was strongly predictive of extent of aortic atherosclerosis and risk of being in the top quartile of aortic atherosclerosis after adjustment for the Framingham Coronary Risk Score (FCRS) or the combination of the FCRS and C-reactive protein ( P <0.0001). The areas under the receiver operating curves predicting the top quartile of gender-specific aortic atherosclerosis were 0.57, 0.60, and 0.75 for models containing the FCRS, the FCRS and C-reactive protein, and the FCRS, C-reactive protein, and the average of calf and thigh MaxV50. Conclusions— Lower-extremity arterial compliance may identify subjects with extensive subclinical atheroscl...

British Journal of Clinical Pharmacology, 2004

Aims Systemic absorption from inhaled glucocorticoids may lead to bone loss. We determined the ex... more Aims Systemic absorption from inhaled glucocorticoids may lead to bone loss. We determined the extent to which their use alone and in addition to shor t courses of oral glucocorticoids was associated with increased prescribing for osteoporosis in a large general practice population. Methods In a cohort study with follow-up of co-prescribing of antiosteoporotic drug therapy in the Irish national prescribing database (1.1 million people over 16 years), we identified 32 081 patients who received inhaled glucocorticoids alone during a 12-month period (following an identical lead-in period). We determined the odds ratio (OR), adjusting for age and gender for the co-prescription of bisphosphonates or other antiosteoporotic therapy with inhaled glucocorticoids by logistic regression. Results The adjusted OR (95% confidence interval) for co-prescribing of bisphosphonates and all inhaled glucocorticoids was 1.87 (1.71, 2.04); 1.58 (1.41, 1.78) for inhaled beclomethasone, 2.11 (1.75, 2.54) for inhaled budesonide and 3.29 (2.65, 4.1) for inhaled fluticasone. The ORs were significantly increased when patients who also received oral glucocorticoids were included and greater still in those under 45 years: 14.03 (10.6, 18.6). The results remained significant when the effects of comorbidity were adjusted for. The odds of receiving bisphosphonate therapy increased linearly with increasing exposure to inhaled glucocorticoids during the study period. Conclusions Treatment with inhaled glucocorticoids in general practice is associated with an increased risk of co-prescribing for antiosteoporotic therapy in a potency-and a doserelated manner. Exposure to a course of oral glucocorticoids doubles this risk. These results suggest that the systemic effects on bone mineral density from using inhaled glucocorticoids may be clinically relevant but may also reflect prescribers' concerns for the development of osteoporosis in these patients.

British Journal of Clinical Pharmacology, 2001

Aims To develop an index of quality prescribing in general practice by investigating the inciden... more Aims To develop an index of quality prescribing in general practice by investigating the incidence of potential drug interactions when medicines were coprescribed within the State supported General Medical Services (GMS) in Ireland.Methods We determined an odds ratio (OR), as a measure of the relative risk of being exposed to a potential interaction, comparing the use of the H2‐receptor antagonist, cimetidine, with that of the noninteracting agents ranitidine, famotidine and nizatidine in users and nonusers of warfarin, phenytoin and theophylline.Results and conclusions In 86 510 prescriptions for the H2–receptor antagonists potentially interacting drugs were dispensed to 8188 (9%) patients in the Eastern Health Board Region of the GMS. We found that prescribers were significantly less likely to use cimetidine (OR = 0.20,95% CI 0.17–0.21, P < 0.001) in those patients who were coprescribed warfarin, suggesting good prescribing practice within the GMS. Similarly there was prefer...

AIDS and Behavior, 2012

Discrimination can influence risk of disease by promoting unhealthy behaviors (e.g., smoking, alc... more Discrimination can influence risk of disease by promoting unhealthy behaviors (e.g., smoking, alcohol use). Whether it influences the formation of high-risk social ties that facilitate HIV transmission is unclear. Using cross-sectional data from a cohort of illicit drug users, this study examined the association between discrimination based on race, drug use and prior incarceration and risky sex and drug ties. Negative binomial regression models were performed. Participants who reported discrimination based on race and drug use had significantly more sex and drug-using ties. But, after accounting for both racial and drug use discrimination, only racial discrimination was associated with increased sex, drug-using, and injecting ties. Drug users who experience discrimination and subsequently develop more sex and drug-using ties, increase their risk of contracting HIV. Future longitudinal studies illuminating the pathways linking discrimination and social network development may guide intervention development and identify drug-using subpopulations at high risk for disease transmission.

American Journal of Psychiatry, 1989

Six women with late luteal phase dysphoric disorder had a significant reduction in depression rat... more Six women with late luteal phase dysphoric disorder had a significant reduction in depression ratings after treatment with evening, but not morning, bright light. Bright light may offer an alternative to the pharmacologic treatment of premenstrual mood disorders.

Circulation, 2004

The recent article by Mitsios et al 1 suggests that atorvastatin does not affect the antiplatelet... more The recent article by Mitsios et al 1 suggests that atorvastatin does not affect the antiplatelet potency of clopidogrel after coadministration for 5 weeks in patients who have suffered from acute coronary syndromes. However, we believe that uncertainty persists regarding a possible interaction. Firstly, the dose of atorvastatin in this study may have been too low to cause a significant drug interaction. Lau et al 2 found that the antiaggregatory effects of clopidogrel were attenuated in a dosedependent manner. Neubauer et al 3 found a non-significant trend of increasing attenuation of the effect of clopidogrel with increasing dose of coadministered cytochrome P450 3A4metabolized statins (simvastatin and atorvastatin). Furthermore, the greatest effect was seen in the initial loading period with clopidogrel and had diminished within 48 hours. These results suggest that any potential interaction may be dose-dependent and that some form of adaptation of platelet function may occur. The use of 2 methods to detect platelet activation-aggregation and flow cytometric measurement of P-selectin expressionwould be expected to increase the chance of detecting a potential interaction. However, we wonder why the P-selectin results were reported in the article by Mitsios et al 1 as changes in mean fluorescence intensity and not as the percentage of activated platelets, which would provide a better indication of the magnitude of platelet inhibition by clopidogrel. Although it is reassuring to find no effect of atorvastatin 10 mg on antiplatelet activity after 5 weeks of coadministration with clopidogrel, we would suggest that further work is required using higher doses of statins in both the acute and chronic phase of statin-clopidogrel use.

Journal of Physical Oceanography, 2018

On the morning of 23 June 2016, a 0.70-m meteotsunami was observed in the English Channel between... more On the morning of 23 June 2016, a 0.70-m meteotsunami was observed in the English Channel between the United Kingdom and France. This wave was measured by several tide gauges and coincided with a heavily precipitating convective system producing 10 m s−1 wind speeds at the 10-m level and 1–2.5-hPa surface pressure anomalies. A combination of precipitation rate cross correlations and NCEP–NCAR Reanalysis 1 data showed that the convective system moved northeastward at 19 ± 2 m s−1. To model the meteotsunami, the finite element model Telemac was forced with an ensemble of prescribed pressure forcings, covering observational uncertainty. Ensembles simulated the observed wave period and arrival times within minutes and wave heights within tens of centimeters. A directly forced wave and a secondary coastal wave were simulated, and these amplified as they propagated. Proudman resonance was responsible for the wave amplification, and the coastal wave resulted from strong refraction of the p...

Journal of Physical Oceanography, Apr 1, 2021

Meteotsunamis are shallow-water waves that, despite often being small (;0.3 m), can cause damage,... more Meteotsunamis are shallow-water waves that, despite often being small (;0.3 m), can cause damage, injuries, and fatalities due to relatively strong currents (.1 m s 21). Previous case studies, modeling, and localized climatologies have indicated that dangerous meteotsunamis can occur across northwest Europe. Using 71 tide gauges across northwest Europe between 2010 and 2017, a regional climatology was made to understand the typical sizes, times, and atmospheric systems that generate meteotsunamis. A total of 349 meteotsunamis (54.0 meteotsunamis per year) were identified with 0.27-0.40-m median wave heights. The largest waves (;1 m high) were measured in France and the Republic of Ireland. Most meteotsunamis were identified in winter (43%-59%), and the fewest identified meteotsunamis occurred in either spring or summer (0%-15%). There was a weak diurnal signal, with most meteotsunami identifications between 1200 and 1859 UTC (30%) and the fewest between 0000 and 0659 UTC (23%). Radar-derived precipitation was used to identify and classify the morphologies of mesoscale precipitating weather systems occurring within 6 h of each meteotsunami. Most mesoscale atmospheric systems were quasi-linear systems (46%) or open-cellular convection (33%), with some nonlinear clusters (17%) and a few isolated cells (4%). These systems occurred under westerly geostrophic flow, with Proudman resonance possible in 43 out of 45 selected meteotsunamis. Because most meteotsunamis occur on cold winter days, with precipitation, and in large tides, wintertime meteotsunamis may be missed by eyewitnesses, helping to explain why previous observationally based case studies of meteotsunamis are documented predominantly in summer.

Journal of Physical Oceanography, 2021

Meteotsunamis are shallow-water waves that, despite often being small (~0.3 m), can cause damage,... more Meteotsunamis are shallow-water waves that, despite often being small (~0.3 m), can cause damage, injuries, and fatalities due to relatively strong currents (>1 m s−1). Previous case studies, modeling, and localized climatologies have indicated that dangerous meteotsunamis can occur across northwest Europe. Using 71 tide gauges across northwest Europe between 2010 and 2017, a regional climatology was made to understand the typical sizes, times, and atmospheric systems that generate meteotsunamis. A total of 349 meteotsunamis (54.0 meteotsunamis per year) were identified with 0.27–0.40-m median wave heights. The largest waves (~1 m high) were measured in France and the Republic of Ireland. Most meteotsunamis were identified in winter (43%–59%), and the fewest identified meteotsunamis occurred in either spring or summer (0%–15%). There was a weak diurnal signal, with most meteotsunami identifications between 1200 and 1859 UTC (30%) and the fewest between 0000 and 0659 UTC (23%). Ra...

Natural Hazards, 2020

Proudman resonance is a primary amplification mechanism for meteotsunamis, which are shallow-wate... more Proudman resonance is a primary amplification mechanism for meteotsunamis, which are shallow-water waves generated by atmospheric forcings. The effect of tides, sloping bathymetry and the speed, amplitude and aspect ratio of the atmospheric forcing on Proudman resonant wave growth are investigated using analytical approximations and numerical models. With tides included, maximum wave growth through Proudman resonance occurred when the atmospheric-forcing speed matched the tidal-wave speed. Growth greater than Proudman resonance occurred with a positive tidal elevation together with a tidal current in the opposite direction to wave propagation, due to linear growth combined with further amplification from wave-flux conservation. Near-Proudman resonant growth occurred when the forced-wave speed or free-wave speed varied by either a small amount, or varied rapidly, around a speed appropriate for Proudman resonance. For a forcing moving at Proudman resonant speed, resultant wave growth ...

The American journal of occupational therapy : official publication of the American Occupational Therapy Association

This study assessed the feasibility and preliminary efficacy of an online-assisted, occupational ... more This study assessed the feasibility and preliminary efficacy of an online-assisted, occupational therapist-delivered, cognitive-behavioral therapy intervention to promote physical function in patients with knee osteoarthritis (KOA). Fifty-seven participants with KOA were randomized 2:1 to the Engage program (eight clinic-based sessions supported by online modules) or usual care. Using analysis of covariance, we estimated Engage's effect on physical function (Western Ontario and McMaster Universities Osteoarthritis Index's Physical Function subscale [WOMAC-PF]) at 6 mo. Data were analyzed on 46 completers. Engage was associated with a small effect (η² = 0.01) on the WOMAC-PF. More Engage participants than controls reported much or very much improvement (45% vs. 13%; p = .03). Satisfaction was high, and 30 of 31 participants attended six sessions or more. An online-supported cognitive-behavioral program for people with KOA delivered by occupational therapists is feasible and m...

Annals of behavioral medicine : a publication of the Society of Behavioral Medicine, Jan 13, 2018

Adverse Childhood Experiences (ACEs) such as sexual and physical violence, serious illness, and b... more Adverse Childhood Experiences (ACEs) such as sexual and physical violence, serious illness, and bereavement have been linked to number of chronic pain conditions in adulthood, and specifically to urologic chronic pelvic pain syndrome (UCPPS). We sought to characterize the prevalence of ACEs in UCPPS using a large well-characterized cohort in comparison with a group of healthy controls. We also sought to determine the association of ACE severity with psychological factors known to impact pain and to determine whether ACEs are associated with patterns of improvement or worsening of symptom over a year of naturalistic observation. For longitudinal analyses we used functional clusters identifying broad classes of (a) improved, (b) worsened, and (c) stable groups for genitourinary pain and urinary symptoms. We employed a mediation/path analysis framework to determine whether ACEs influenced 1 year outcomes directly, or indirectly through worse perceptions of physical well-being. ACE seve...

The Journal of pediatrics, Jan 25, 2018

To evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of... more To evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and pediatric enthesitis-related arthritis), psoriasis, and Crohn's disease. This analysis included data from 7 global, randomized, and open-label AbbVie-sponsored clinical trials of adalimumab and their open-label extensions conducted between September 2002 and December 31, 2015 (cutoff date for ongoing studies). Patients who received ≥1 dose of adalimumab subcutaneously were included. Adverse events that occurred after the first dose of adalimumab and up to 70 days (5 half-lives) after the last dose were reported and events per 100 patient-years were calculated. The analysis included 577 pediatric patients, representing 1440.7 patient-years of adalimumab exposure. Across indications, the most commonly reported adverse events (events/100 patient-years) were upper respiratory tract infections (24.3), nasophar...

Pain, Jan 28, 2018

Chronic Overlapping Pain Conditions (COPCs) are characterized by aberrant central nervous system ... more Chronic Overlapping Pain Conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This 'centralized pain' phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here we used three cohorts, including patients with Urologic Chronic Pelvic Pain Syndrome (UCPPS), a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified two general factors in all three cohorts, one characterized by a broad increased sensitivity to internal somatic sensations and environmental stimuli, and diffuse pain, termed Generaliz...

Oncology nursing forum, Jan 2, 2018

To explore associations between quantitative sensory testing (QST) and pretreatment pain, physica... more To explore associations between quantitative sensory testing (QST) and pretreatment pain, physical, and psychological characteristics in women with breast cancer. 41 women with treatment-naive stage 0-III breast cancer at the University of Michigan Comprehensive Cancer Center in Ann Arbor. Participants completed self-report surveys and QST within the month before breast surgery. Pressure pain thresholds (PPTs) were measured bilaterally at each trapezius with a manual QST algometer. PPT values were split, yielding low, moderate, and high pain sensitivity subgroups. Subgroup self-reported characteristics were compared using Spearman's correlation, chi-square, and one-way analysis of variance. Lower PPT (higher sensitivity) was associated with higher levels of pain interference and maladaptive pain cognitions. The high-sensitivity group reported higher pain severities, interference, and catastrophizing and lower belief in internal locus of pain control than the low-sensitivity grou...

The journal of pain : official journal of the American Pain Society, Dec 30, 2016

Somatic awareness (SA) refers to heightened sensitivity to a variety of physical sensations and s... more Somatic awareness (SA) refers to heightened sensitivity to a variety of physical sensations and symptoms. Few attempts have been made to dissociate the relationship of SA and affective symptoms with pain outcomes. We used a validated measure of mood and anxiety symptoms that includes questions related to SA to predict the number of tender points found on physical examination in a large cross-sectional community sample (the Midlife in the United States [MIDUS] Biomarker study). General distress, positive affect, and SA, which were all significantly associated with tender point number in bivariate analyses, were used as predictors of the number of tender points in a multivariate negative binomial regression model. In this model a greater number of tender points was associated with higher levels of SA (p = .02) but not general distress (p = .13) or positive affect (p = .50). Follow-up mediation analyses indicated that the relationship between general distress and tender points was part...

Therapeutic advances in drug safety, 2011

A number of drug classes are licensed for the treatment of osteoporosis including bisphosphonates... more A number of drug classes are licensed for the treatment of osteoporosis including bisphosphonates, recombinant human parathyroid hormone (PTH), strontium, hormone replacement therapy (HRT), selective oestrogen receptor modulators (SERMS) and denosumab. This review discusses the safety of osteoporosis treatments and their efficacies. Recent concerns about the safety of calcium and high-dose vitamin D are discussed. Bisphosphonates have substantial postmarketing experience and a clearer picture of safety issues is emerging. Along with the well recognized effects on the gastrointestinal tract and kidney function, recently described adverse effects such as osteonecrosis of the jaw, oesophageal cancer, atrial fibrillation, subtrochanteric femur fractures and ocular complications of bisphosphonate therapy are discussed. Therapy with PTH is limited to two years' duration because of the development of osteogenic sarcomas in animal studies, which appeared related to dose, duration and ti...

Journal of Pediatric Hematology/Oncology, 2002

The Journal of Pain, 2014

Aromatase inhibitors (AI), which are used to treat breast cancer, inhibit estrogen production in ... more Aromatase inhibitors (AI), which are used to treat breast cancer, inhibit estrogen production in postmenopausal women. AI-associated musculoskeletal symptoms (AIMSS) occur in approximately half of treated women, and lead to treatment discontinuation in 20-30%. The etiology may be due in part to estrogen deprivation. In premenopausal women, lower estrogen levels have been associated with increased pain, as well as with impairment of descending pain inhibitory pathways, which may be a risk factor for developing chronic pain. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AIMSS. Fifty postmenopausal breast cancer patients underwent pressure pain testing and conditioned pain modulation (CPM) assessment prior to AI initiation and after 3 and 6 months. At baseline, 26 of 40 (65%) assessed patients demonstrated impaired CPM, which was greater in those who had previously received chemotherapy (p=0.006). No statistically significant change in pressure pain threshold or CPM was identified following estrogen deprivation. In

Circulation, 2004

Background— Noninvasive measures of arterial compliance may be useful for the detection of subcli... more Background— Noninvasive measures of arterial compliance may be useful for the detection of subclinical atherosclerosis. Methods and Results— Measures of calf and thigh arterial compliance (MaxV50) were recorded in 267 subjects who also underwent MRI of the distal aorta to quantify distal aorta atherosclerosis. The average of calf and thigh MaxV50 was strongly predictive of extent of aortic atherosclerosis and risk of being in the top quartile of aortic atherosclerosis after adjustment for the Framingham Coronary Risk Score (FCRS) or the combination of the FCRS and C-reactive protein ( P <0.0001). The areas under the receiver operating curves predicting the top quartile of gender-specific aortic atherosclerosis were 0.57, 0.60, and 0.75 for models containing the FCRS, the FCRS and C-reactive protein, and the FCRS, C-reactive protein, and the average of calf and thigh MaxV50. Conclusions— Lower-extremity arterial compliance may identify subjects with extensive subclinical atheroscl...

British Journal of Clinical Pharmacology, 2004

Aims Systemic absorption from inhaled glucocorticoids may lead to bone loss. We determined the ex... more Aims Systemic absorption from inhaled glucocorticoids may lead to bone loss. We determined the extent to which their use alone and in addition to shor t courses of oral glucocorticoids was associated with increased prescribing for osteoporosis in a large general practice population. Methods In a cohort study with follow-up of co-prescribing of antiosteoporotic drug therapy in the Irish national prescribing database (1.1 million people over 16 years), we identified 32 081 patients who received inhaled glucocorticoids alone during a 12-month period (following an identical lead-in period). We determined the odds ratio (OR), adjusting for age and gender for the co-prescription of bisphosphonates or other antiosteoporotic therapy with inhaled glucocorticoids by logistic regression. Results The adjusted OR (95% confidence interval) for co-prescribing of bisphosphonates and all inhaled glucocorticoids was 1.87 (1.71, 2.04); 1.58 (1.41, 1.78) for inhaled beclomethasone, 2.11 (1.75, 2.54) for inhaled budesonide and 3.29 (2.65, 4.1) for inhaled fluticasone. The ORs were significantly increased when patients who also received oral glucocorticoids were included and greater still in those under 45 years: 14.03 (10.6, 18.6). The results remained significant when the effects of comorbidity were adjusted for. The odds of receiving bisphosphonate therapy increased linearly with increasing exposure to inhaled glucocorticoids during the study period. Conclusions Treatment with inhaled glucocorticoids in general practice is associated with an increased risk of co-prescribing for antiosteoporotic therapy in a potency-and a doserelated manner. Exposure to a course of oral glucocorticoids doubles this risk. These results suggest that the systemic effects on bone mineral density from using inhaled glucocorticoids may be clinically relevant but may also reflect prescribers' concerns for the development of osteoporosis in these patients.

British Journal of Clinical Pharmacology, 2001

Aims To develop an index of quality prescribing in general practice by investigating the inciden... more Aims To develop an index of quality prescribing in general practice by investigating the incidence of potential drug interactions when medicines were coprescribed within the State supported General Medical Services (GMS) in Ireland.Methods We determined an odds ratio (OR), as a measure of the relative risk of being exposed to a potential interaction, comparing the use of the H2‐receptor antagonist, cimetidine, with that of the noninteracting agents ranitidine, famotidine and nizatidine in users and nonusers of warfarin, phenytoin and theophylline.Results and conclusions In 86 510 prescriptions for the H2–receptor antagonists potentially interacting drugs were dispensed to 8188 (9%) patients in the Eastern Health Board Region of the GMS. We found that prescribers were significantly less likely to use cimetidine (OR = 0.20,95% CI 0.17–0.21, P < 0.001) in those patients who were coprescribed warfarin, suggesting good prescribing practice within the GMS. Similarly there was prefer...

AIDS and Behavior, 2012

Discrimination can influence risk of disease by promoting unhealthy behaviors (e.g., smoking, alc... more Discrimination can influence risk of disease by promoting unhealthy behaviors (e.g., smoking, alcohol use). Whether it influences the formation of high-risk social ties that facilitate HIV transmission is unclear. Using cross-sectional data from a cohort of illicit drug users, this study examined the association between discrimination based on race, drug use and prior incarceration and risky sex and drug ties. Negative binomial regression models were performed. Participants who reported discrimination based on race and drug use had significantly more sex and drug-using ties. But, after accounting for both racial and drug use discrimination, only racial discrimination was associated with increased sex, drug-using, and injecting ties. Drug users who experience discrimination and subsequently develop more sex and drug-using ties, increase their risk of contracting HIV. Future longitudinal studies illuminating the pathways linking discrimination and social network development may guide intervention development and identify drug-using subpopulations at high risk for disease transmission.

American Journal of Psychiatry, 1989

Six women with late luteal phase dysphoric disorder had a significant reduction in depression rat... more Six women with late luteal phase dysphoric disorder had a significant reduction in depression ratings after treatment with evening, but not morning, bright light. Bright light may offer an alternative to the pharmacologic treatment of premenstrual mood disorders.

Circulation, 2004

The recent article by Mitsios et al 1 suggests that atorvastatin does not affect the antiplatelet... more The recent article by Mitsios et al 1 suggests that atorvastatin does not affect the antiplatelet potency of clopidogrel after coadministration for 5 weeks in patients who have suffered from acute coronary syndromes. However, we believe that uncertainty persists regarding a possible interaction. Firstly, the dose of atorvastatin in this study may have been too low to cause a significant drug interaction. Lau et al 2 found that the antiaggregatory effects of clopidogrel were attenuated in a dosedependent manner. Neubauer et al 3 found a non-significant trend of increasing attenuation of the effect of clopidogrel with increasing dose of coadministered cytochrome P450 3A4metabolized statins (simvastatin and atorvastatin). Furthermore, the greatest effect was seen in the initial loading period with clopidogrel and had diminished within 48 hours. These results suggest that any potential interaction may be dose-dependent and that some form of adaptation of platelet function may occur. The use of 2 methods to detect platelet activation-aggregation and flow cytometric measurement of P-selectin expressionwould be expected to increase the chance of detecting a potential interaction. However, we wonder why the P-selectin results were reported in the article by Mitsios et al 1 as changes in mean fluorescence intensity and not as the percentage of activated platelets, which would provide a better indication of the magnitude of platelet inhibition by clopidogrel. Although it is reassuring to find no effect of atorvastatin 10 mg on antiplatelet activity after 5 weeks of coadministration with clopidogrel, we would suggest that further work is required using higher doses of statins in both the acute and chronic phase of statin-clopidogrel use.

Journal of Physical Oceanography, 2018

On the morning of 23 June 2016, a 0.70-m meteotsunami was observed in the English Channel between... more On the morning of 23 June 2016, a 0.70-m meteotsunami was observed in the English Channel between the United Kingdom and France. This wave was measured by several tide gauges and coincided with a heavily precipitating convective system producing 10 m s−1 wind speeds at the 10-m level and 1–2.5-hPa surface pressure anomalies. A combination of precipitation rate cross correlations and NCEP–NCAR Reanalysis 1 data showed that the convective system moved northeastward at 19 ± 2 m s−1. To model the meteotsunami, the finite element model Telemac was forced with an ensemble of prescribed pressure forcings, covering observational uncertainty. Ensembles simulated the observed wave period and arrival times within minutes and wave heights within tens of centimeters. A directly forced wave and a secondary coastal wave were simulated, and these amplified as they propagated. Proudman resonance was responsible for the wave amplification, and the coastal wave resulted from strong refraction of the p...