Thomas Jemielita

Unconventional Gas and Oil Drilling Is Associated with Increased Hospital Utilization Rates

Over the past ten years, unconventional gas and oil drilling (UGOD) has markedly expanded in the United States. Despite substantial increases in well drilling, the health consequences of UGOD toxicant exposure remain unclear. This study examines an association between wells and healthcare use by zip code from 2007 to 2011 in Pennsylvania. Inpatient discharge databases from the Pennsylvania Healthcare Cost Containment Council were correlated with active wells by zip code in three counties in Pennsylvania. For overall inpatient prevalence rates and 25 specific medical categories, the association of inpatient prevalence rates with number of wells per zip code and, separately, with wells per km2 (separated into quantiles and defined as well density) were estimated using fixed-effects Poisson models. To account for multiple comparisons, a Bonferroni correction with associations of p<0.00096 was considered statistically significant. Cardiology inpatient prevalence rates were significantly associated with number of wells per zip code (p<0.00096) and wells per km2 (p<0.00096) while neurology inpatient prevalence rates were significantly associated with wells per km2 (p<0.00096). Furthermore, evidence also supported an association between well density and inpatient prevalence rates for the medical categories of dermatology, neurology, oncology, and urology. These data suggest that UGOD wells, which dramatically increased in the past decade, were associated with increased inpatient prevalence rates within specific medical categories in Pennsylvania. Further studies are necessary to address healthcare costs of UGOD and determine whether specific toxicants or combinations are associated with organ-specific responses.

Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort Study

Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence interval [95% CI], 293-533) and 323 (95% CI, 216-481) fractures per 10,000 person-years, respectively. These rates were 2- to 3-fold higher than published general population rates. The only gender difference in fracture risk was a 2.6-fold higher risk in males aged ≥15 years (570/10,000 person-years, adjusted P=0.04). In multivariable analysis, advanced pubertal stage, greater height Z-score, difficulty walking, and higher average log-transformed parathyroid hormone level were independently associated with greater fracture risk (all P≤0.04). Phosphate binder treatment (predominantly calcium-based) was associated with lower fracture risk (hazard ratio, 0.37; 95% CI, 0.15-0.91; P=0.03). Participation in more than one team sport was associated with higher risk (hazard ratio, 4.87; 95% CI, 2.21-10.75; P<0.001). In conclusion, children with CKD have a high burden of fracture. Regarding modifiable factors, higher average parathyroid hormone level was associated with greater risk of fracture, whereas phosphate binder use was protective in this cohort.

Assessing the risk of incident hypertension and chronic kidney disease after exposure to shock wave lithotripsy and ureteroscopy

In this study we sought to determine if among individuals with urolithiasis, extracorporeal shock wave lithotripsy (SWL) and ureteroscopy are associated with a higher risk of incident arterial hypertension (HTN) and/or chronic kidney disease (CKD). This was measured in a population-based retrospective study of 11,570 participants with incident urolithiasis and 127,464 without urolithiasis in The Health Improvement Network. Patients with pre-existing HTN and CKD were excluded. The study included 1319 and 919 urolithiasis patients with at least one SWL or URS procedure, respectively. Multivariable Cox regression was used to estimate the hazard ratio for incident CKD stage 3–5 and HTN in separate analyses. Over a median of 3.7 and 4.1 years, 1423 and 595 of urolithiasis participants developed HTN and CKD, respectively. Urolithiasis was associated with a significant hazard ratio each for HTN of 1.42 (95% CI: 1.35, 1.51) and for CKD of 1.82 (1.67, 1.98). SWL was associated with a significant increased risk of HTN 1.34 (1.15, 1.57), while ureteroscopy was not. When further stratified as SWL to the kidney or ureter, only SWL to the kidney was significantly and independently associated with HTN 1.40 (1.19, 1.66). Neither SWL nor ureteroscopy was associated with incident CKD. Since urolithiasis itself was associated with a hazard ratio of 1.42 for HTN, an individual who undergoes SWL to the kidney can be expected to have a significantly increased hazard ratio for HTN of 1.96 (1.67, 2.29) compared to an individual without urolithiasis.

Characterization of Whole Body Pain in Urological Chronic Pelvic Pain Syndrome at Baseline: A MAPP Research Network Study

Purpose: We characterized the location and spatial distribution of whole body pain in patients with urological chronic pelvic pain syndrome using a body map. We also compared the severity of urinary symptoms, pelvic pain, nonpelvic pain and psychosocial health among patients with different pain patterns. Materials and Methods: A total of 233 women and 191 men with urological chronic pelvic pain syndrome enrolled in a multicenter, 1‐year observational study completed a battery of baseline measures, including a body map describing the location of pain during the last week. Participants were categorized with pelvic pain if they reported pain in the abdomen and pelvis only. Participants who reported pain beyond the pelvis were further divided into 2 subgroups based on the number of broader body regions affected by pain, including an intermediate group with 1 or 2 additional regions outside the pelvis and a widespread pain group with 3 to 7 additional regions. Results: Of the 424 enrolled patients 25% reported pelvic pain only and 75% reported pain beyond the pelvis, of whom 38% reported widespread pain. Participants with a greater number of pain locations had greater nonpelvic pain severity (p <0.0001), sleep disturbance (p = 0.035), depression (p = 0.005), anxiety (p = 0.011), psychological stress (p = 0.005) and negative affect scores (p = 0.0004), and worse quality of life (p ≤0.021). No difference in pelvic pain and urinary symptom severity was observed according to increasing pain distribution. Conclusions: Three‐quarters of the men and women with urological chronic pelvic pain syndrome reported pain outside the pelvis. Widespread pain was associated with greater severity of nonpelvic pain symptoms, poorer psychosocial health and worse quality of life but not with worse pelvic pain or urinary symptoms.

Correction: Unconventional Gas and Oil Drilling Is Associated with Increased Hospital Utilization Rates

The Data Availability statement is incorrect. The correct statement is: All relevant data are available via Figshare (http://dx.doi.org/10.6084/m9.figshare.1508617).

Oral Antibiotic Exposure and Kidney Stone Disease

Background Although intestinal and urinary microbiome perturbations are associated with nephrolithiasis, whether antibiotics are a risk factor for this condition remains unknown.Methods We determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based, case-control study nested within 641 general practices providing electronic health record data for >13 million children and adults from 1994 to 2015 in the United Kingdom. We used incidence density sampling to match 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at date of diagnosis (index date). Conditional logistic regression models were adjusted for the rate of health care encounters, comorbidities, urinary tract infections, and use of thiazide and loop diuretics, proton-pump inhibitors, and statins.Results Exposure to any of five different antibiotic classes 3-12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (P<0.001) and 3-6 months before index date (P<0.001), with all but broad-spectrum penicillins remaining statistically significant 3-5 years from exposure.Conclusions Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children.

Variability in measures of mineral metabolism in children on hemodialysis: impact on clinical decision-making

BackgroundVariability in measures of mineral metabolism has not been studied in pediatric end stage kidney disease. We sought to determine the intra-individual variability in measures of mineral metabolism in children on hemodialysis (HD) and its impact on clinical decision-making.MethodsWe conducted a prospective single-center study of children (3.6–17.3 years old) on chronic HD. Serial twice weekly measures of serum calcium, phosphate and intact parathyroid hormone (PTH), as well as weekly measures of fibroblast growth factor 23 (FGF23) and vitamin D metabolites, were obtained over a 12-week period in 10 children. Samples (n = 226) were assayed in a single batch at the end of the study.ResultsThe median intra-individual coefficient of variation (CV) calculated by 4-week blocks was 5.1–6.5% for calcium, 9.5–14.9% for phosphate and 32.7–33.4% for PTH. The median overall CV for FGF23 was 44.4%. Using the first value of each block as a reference, subsequent values would dictate a discrepant management decision 33–56%, 19–28%, and 30–33% of the time for calcium, phosphate, and PTH, respectively. Adjusting for sex and age, most of the variability in phosphate and PTH was attributable to within-participant variability. For calcium, 49% of the variability was attributable to day of blood collection (Monday vs. Friday). The median (range) of an individual participant’s values within clinical target ranges was 55% (26–86%) for calcium, 58% (0–96%) for phosphate, and 21% (0–64%) for PTH.ConclusionsThere is considerable intra-individual variability in measures of mineral metabolism that serve as surrogate markers for bone health in children on HD. Within a 4-week period, at least 20–30% of measures would dictate a discrepant decision from the referent measure of that month. These findings have important implications for clinical decision-making and underscore the need to base therapeutic decisions on trends rather than single measurements.

Improved power in crossover designs through linear combinations of baselines

In a crossover design in the absence of any carryover effect, including period-specific baselines as covariates in an analysis of covariance, is known to increase the precision of the estimated treatment effect. The extent of the efficiency gain is a function of the joint covariance structure of the baselines and post-treatment responses, as well as the metric used to incorporate the baselines into the analysis. Here, we show how the underlying covariance structure can be leveraged to find an optimal linear combination of baselines so as to minimize the theoretical variance of the analysis of covariance-based estimated treatment effect. Our work is relevant to complete designs with up to four periods, specifically the 2 × 2, 3 × 3, and 4 × 4. Given that the optimal linear combination of baselines is a function of the covariance structure, which in practice is unknown, we propose an adaptive method. Here, the covariance structure is chosen using information criterion to guide the choice of the linear combination of baselines. Evaluation of the proposed approach suggests that the type I error rate is maintained. Moreover, relative to previously published methods, sizeable gains in power are possible with this method. Results from a 2 × 2 trial exploring renal function, and a 3 × 3 trial with heart rate as the outcome, are used to illustrate the methods. Copyright

A Case-Crossover Study of Urological Chronic Pelvic Pain Syndrome Flare Triggers in the MAPP Research Network

Purpose: Although many factors have been proposed to trigger symptom exacerbations (flares) in patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, few studies have investigated these factors empirically. Therefore, we embedded a case‐crossover study in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain longitudinal study to evaluate a range of patient reported triggers. Materials and Methods: We assessed exposure to proposed triggers, including diet, physical activities, sedentary behaviors, stress, sexual activities, infection‐like symptoms and allergies, by questionnaire a maximum of 3 times when participants reported flares and at 3 randomly selected times. We compared participant preflare to nonflare exposures by conditional logistic regression. Results: In our full analytical sample of 292 participants only 2 factors, including recent sexual activity (OR 1.44, 95% CI 1.06–1.96) and urinary tract infection symptoms (OR 3.39, 95% CI 2.02–5.68), which may overlap with those of flares, were associated with flare onset. On subanalyses restricted to flares with specific suspected triggers additional positive associations were observed for some factors such as certain dietary factors, abdominal muscle exercises, and vaginal infection‐like symptoms and fever, but not for other factors (eg stress). Conclusions: Except for sexual activity our findings suggest that patient reported triggers may be individual or group specific, or they may not contribute to flares. These findings suggest caution in following rigid, global flare prevention strategies and support additional research to develop evidence‐based strategies.

MP29-12 USE OF A BODY PAIN MAP TO CHARACTERIZE UROLOGIC CHRONIC PELVIC PAIN SYNDROME – A MAPP RESEARCH NETWORK STUDY

H. Henry Lai*, St Louis, MO; Thomas Jemielita, Philadelphia, PA; Catherine S. Bradley, Iowa City, IA; Bruce Naliboff, Los Angeles, CA; Robert Gereau IV, St Louis, MO; David A. Williams, Ann Arbor, MI; Karl Kreder, Iowa City, IA; J. Quentin Clemens, Ann Arbor, MI; Larissa V. Rodriguez, Los Angeles, CA; John N. Krieger, Seattle, WA; John T. Farrar, Nancy Robinson, J. Richard Landis, Philadelphia, PA