Environmental factors shaping the gut microbiome in a Dutch population.

The gut microbiome is associated with diverse diseases1-3, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.

Molnupiravir; molecular and functional descriptors of mitochondrial safety.

Molnupiravir is an orally active nucleoside analog antiviral drug that recently was approved by the U.S. FDA for emergency treatment of adult patients infected with the SARS-CoV-2 (COVID-19) virus and at risk for severe progression. The active form of the drug, N-hydroxycytidine (NHC) triphosphate competes for incorporation by RNA-dependent RNA-polymerase (RdRp) into the replicating viral genome resulting in mutations and arrest of the replicating virus. Historically, some nucleoside analog antiviral drugs have been found to lack specificity for the virus and also inhibit replication and/or expression of the mitochondrial genome. The objective of the present study was to test whether molnupiravir and/or NHC also target mitochondrial DNA polymerase gamma (PolG) or RNA polymerase (POLRMT) activity to inhibit the replication and/or expression of the mitochondrial genome leading to impaired mitochondrial function. Human-derived HepG2 cells were exposed for 48 h in culture to increasing concentrations of either molnupiravir or NHC after which cytotoxicity, mtDNA copy number and mitochondrial gene expression were determined. The phenotypic endpoint, mitochondrial respiration, was measured with the Seahorse® XF96 Extracellular Flux Analyzer. Both molnupiravir and NHC were cytotoxic at concentrations of ≥10 µM. However, at non-cytotoxic concentrations, neither significantly altered mitochondrial gene dose or transcription, or mitochondrial respiration. From this we conclude that mitochondrial toxicity is not a primary off target in the mechanism of cytotoxicity for either molnupiravir or its active metabolite NHC in the HepG2 cell line.

Remdesivir; molecular and functional measures of mitochondrial safety.

Remdesivir is one of a few antiviral drugs approved for treating severe cases of coronavirus 2 (SARS-CoV-2) infection in hospitalized patients. The prodrug is a nucleoside analog that interferes with viral replication by inhibiting viral RNA-dependent RNA polymerase. The drug has also been shown to be a weak inhibitor of human mitochondrial RNA polymerase, leaving open the possibility of mitochondrial off-targets and toxicity. The investigation was designed to explore whether remdesivir causes mitochondrial toxicity, using both genomic and functional parameters in the assessment. Human-derived HepG2 liver cells were exposed for up to 48 h in culture to increasing concentrations of remdesivir. At sub-cytotoxic concentrations (<1 µM), the drug failed to alter either the number of copies or the expression of the mitochondrial genome. mtDNA copy number was unaffected as was the relative rates of expression of mtDNA-encoded and nuclear encoded subunits of complexes I and IV of the mitochondrial respiratory chain. Consistent with this is the observation that remdesivir was without effect on mitochondrial respiration, including basal respiration, proton leak, maximum uncoupled respiration, spare respiratory capacity or coupling efficiency. We conclude that although remdesivir has weak inhibitory activity towards mitochondrial RNA polymerase, mitochondria are not primary off-targets for the mechanism of cytotoxicity of the drug.

Hand strength and dexterity in individuals with hand eczema.

BACKGROUND: Patients with hand eczema often describe symptoms such as pain, clumsiness and difficulty flexing their fingers, thus impairing the function of the hand. OBJECTIVE: The aim of this study was to investigate whether hand eczema is associated with a measurable impairment of hand strength and dexterity. We also studied the relationship between hand function and the ability to perform activities of daily living (ADL), pain level and quality of life measured with the Dermatology Life Quality Index (DLQI). METHODS: Twenty-one participants with ongoing hand eczema were examined with well-established methods for measuring hand grip strength, pinch strength and dexterity. A questionnaire was designed to investigate perceived ability to perform ADL. The participants were also asked to grade their current pain level, and the DLQI was used to assess the participants' quality of life. A group of 12 participants was reinvestigated when healed. RESULTS: The participants demonstrated a significant improvement in all functional tests when healed. There was a strong correlation between ADL and both dexterity and hand grip strength. There was also a strong correlation between ADL and pain. All participants reported some difficulty performing ADL. CONCLUSIONS: Our results suggest that ongoing hand eczema may lead to a measurable decrease of strength and dexterity of the hand, leading to an impairment of the ability to perform ADL and consequently to a poorer quality of life.

Nationwide study of appendicitis in children.

BACKGROUND: Paediatric surgical care is increasingly being centralized away from low-volume centres, and prehospital delay is considered a risk factor for more complicated appendicitis. The aim of this study was to determine the incidence of paediatric appendicitis in Sweden, and to assess whether distance to the hospital was a risk factor for complicated disease. METHODS: A nationwide cohort study of all paediatric appendicitis cases in Sweden, 2001-2014, was undertaken, including incidence of disease in different population strata, with trends over time. The risk of complicated disease was determined by regression methods, with travel time as the primary exposure and individual-level socioeconomic determinants as independent variables. RESULTS: Some 38 939 children with appendicitis were identified. Of these, 16·8 per cent had complicated disease, and the estimated risk of paediatric appendicitis by age 18 years was 2·5 per cent. Travel time to the treating hospital was not associated with complicated disease (adjusted odds ratio (OR) 1·00 (95 per cent c.i. 0·96 to 1·05) per 30-min increase; P = 0·934). Level of education (P = 0·177) and family income (P = 0·120) were not independently associated with increased risk of complicated disease. Parental unemployment (adjusted OR 1·17, 95 per cent c.i. 1·05 to 1·32; P = 0·006) and having parents born outside Sweden (1 parent born in Sweden: adjusted OR 1·12, 1·01 to 1·25; both parents born outside Sweden: adjusted OR 1·32, 1·18 to 1·47; P < 0·001) were associated with an increased risk of complicated appendicitis. CONCLUSION: Every sixth child diagnosed with appendicitis in Sweden has a more complicated course of disease. Geographical distance to the surgical facility was not a risk factor for complicated appendicitis.

ANTECEDENTES: La atención quirúrgica pediátrica está cada vez más centralizada lejos de los centros de bajo volumen, y el retraso pre-hospitalario se considera un factor de riesgo para las apendicitis más complicadas. El objetivo de este estudio fue determinar la incidencia de apendicitis pediátrica en Suecia y evaluar si la distancia al hospital era un factor de riesgo para una enfermedad complicada. MÉTODOS: Se analizó un estudio de cohortes a nivel nacional que incluyó todos los casos de apendicitis pediátrica en Suecia durante el periodo 2001-2014, incluida la incidencia de la enfermedad en diferentes estratos de la población y las tendencias a lo largo del tiempo. El riesgo de enfermedad complicada se determinó mediante métodos de regresión, con el tiempo de viaje como exposición primaria y los determinantes socioeconómicos a nivel individual como variables independientes. RESULTADOS: Se identificaron 38.939 casos de apendicitis pediátrica. De estos, el 17% eran complicados y el riesgo estimado de apendicitis pediátrica a los 18 años era del 2,5%. El tiempo de viaje al hospital de tratamiento no se asoció con una enfermedad complicada (razón de oportunidades, odds ratio OR ajustada 1,00 (i.c. del 95%: 0,96 a 1,05) por aumentos de 30 minutos, P = 0,93). El nivel de educación (P = 0,18) y los ingresos familiares (P = 0,120) no se asociaron de forma independiente con un aumento del riesgo de enfermedad complicada. El desempleo de los padres (OR ajustada 1,17 (1,05 a 1,32), P = 0,006) y tener padres nacidos fuera de Suecia se asociaron con un mayor riesgo de apendicitis complicada (P < 0,001; un progenitor nacido en Suecia: OR ajustada 1,12 (1,01 a 1,25), ambos progenitores nacidos fuera de Suecia: OR ajustada 1,32 (1,18 a 1,47)). CONCLUSIÓN: Uno de cada seis niños diagnosticados de apendicitis en Suecia sufre un curso de enfermedad más complicado. La distancia geográfica al hospital donde se llevó a cabo la cirugía no fue un factor de riesgo para la apendicitis complicada.

Population-based incidence rate of inpatient and outpatient surgical procedures in a high-income country.

BACKGROUND: The WHO and the World Bank ask countries to report the national volume of surgery. This report describes these data for Sweden, a high-income country. METHODS: In an 8-year population-based observational cohort study, all inpatient and outpatient care in the public and private sectors was detected in the Swedish National Patient Register and screened for the occurrence of surgery. The entire Swedish population was eligible for inclusion. All patients attending healthcare for any disease were included. Incidence rates of surgery and likelihood of surgery were calculated, with trends over time, and correlation with sex, age and disease category. RESULTS: Almost one in three hospitalizations involved a surgical procedure (30·6 per cent). The incidence rate of surgery exceeded 17 480 operations per 100 000 person-years, and at least 58·5 per cent of all surgery was performed in an outpatient setting (range 58·5 to 71·6 per cent). Incidence rates of surgery increased every year by 5·2 (95 per cent c.i. 4·2 to 6·1) per cent (P < 0·001), predominantly owing to more outpatient surgery. Women had a 9·8 (95 per cent c.i. 5·6 to 14·0) per cent higher adjusted incidence rate of surgery than men (P < 0·001), mainly explained by more surgery during their fertile years. Incidence rates peaked in the elderly for both women and men, and varied between disease categories. CONCLUSION: Population requirements for surgery are greater than previously reported, and more than half of all surgery is performed in outpatient settings. Distributions of age, sex and disease influence estimates of population surgical demand, and should be accounted for in future global and national projections of surgical public health needs.

Wet work exposure and hand eczema among healthcare workers: a cross-sectional study.

BACKGROUND: Hand eczema is more common in healthcare workers than in the general population. Hands are subject to changing occupational exposures as a result of mandatory hygiene regulations for healthcare workers. OBJECTIVES: To describe exposure to hygiene procedures and investigate the associations between occupational hand washing, use of nonsterile gloves and hand disinfectant, and self-reported hand eczema. METHODS: This was a cross-sectional study; an electronic questionnaire was distributed to 28 762 hospital employees in southern Sweden. Nurses, assistant nurses or physicians constituted the group of healthcare workers analysed. Adjustments were made for sex, age, wet work at home, lifestyle factors and atopic dermatitis. RESULTS: In total, 12 288 (43%) responded, including 9051 healthcare workers. In this group the 1-year prevalence of self-reported hand eczema was 21%. On a daily basis, 30% reported hand washing with soap > 20 times at work, 45% used hand disinfectants > 50 times and 54% wore nonsterile gloves for > 2 h. After adjustment for confounding factors, a dose-dependent association with self-reported hand eczema was found for the daily number of hand washes with soap at work and time working with disposable gloves but not for alcoholic disinfectant use. Hand washing outside work was not associated with self-reported hand eczema in the adjusted multivariate analysis. CONCLUSIONS: In this study, we found a higher 1-year prevalence of self-reported hand eczema among Swedish healthcare workers than reported in the general population. Hand washing with soap and use of disposable gloves were associated with the occurrence of self-reported hand eczema in a dose-dependent way. Use of hand disinfectant was not associated with self-reported hand eczema.

Recent hip fracture trends in Sweden and Denmark with age-period-cohort effects.

This study used nationwide hip fracture data from Denmark and Sweden during 1987-2010 to examine effects of (birth) cohort and period. We found that time trends, cohort, and period effects were different in the two countries. Results also indicated that hip fracture rates may increase in the not so far future. INTRODUCTION: The reasons for the downturn in hip fracture rates remain largely unclear but circumstances earlier in life seem important. METHODS: We ascertained hip fractures in the populations ≥50 years in Denmark and Sweden in national discharge registers. Country- and sex-specific age-period-cohort (APC) effects during 1987-2010 were evaluated by log-likelihood estimates in Poisson regression models presented as incidence rate ratios (IRR). RESULTS: There were 399,596 hip fractures in SE and 248,773 in DK. Age-standardized hip fracture rate was stable in SE men but decreased in SE women and in DK. Combined period + cohort effects were generally stronger in SE than DK and in women than men. IRR per period ranged from 1.05 to 1.30 in SE and 0.95 to 1.21 in DK. IRR per birth cohort ranged from 1.07 to 3.13 in SE and 0.77 to 1.67 in DK. Relative period effects decreased with successive period in SE and described a convex curve in DK. Relative cohort effects increased with successive birth cohort in both countries but with lower risks for DK women and men and SE women born around the 1930s (age 75-86 years today and responsible for most hip fractures) partly explaining the recent downturn. Men and women born thereafter however seem to have a higher hip fracture risk, and we expect a reversal of the present decline in rates, with increasing hip fracture rates in both Denmark and Sweden during the upcoming decade. CONCLUSIONS: Time trends, cohort, and period effects were different in SE and DK. This may reflect differences in general health as evident in known differences in life expectancy, healthcare organization, and prevention such as use of anti-osteoporosis drugs. Analyses indicate that hip fracture rates may increase in the not so far future.

Current and future impact of osteoarthritis on health care: a population-based study with projections to year 2032.

OBJECTIVE: To estimate the current and future (to year 2032) impact of osteoarthritis (OA) health care seeking. METHOD: Population-based study with prospectively ascertained data from the Skåne Healthcare Register (SHR), Sweden, encompassing more than 15 million person-years of primary and specialist outpatient care and hospitalizations. We studied all Skåne region residents aged ≥45 by the end of 2012 (n = 531, 254) and determined the prevalence of doctor-diagnosed OA defined as the proportion of the prevalent population that had received a diagnosis of OA of the knee, hip, hand, or other locations except the spine between 1999 and 2012. We projected consultation prevalence of OA until year 2032 using Statistics Sweden's (SCB) projected age and sex structure and prevalence of overweight and obesity. RESULTS: In 2012 the proportion of population aged ≥45 with any doctor-diagnosed OA was 26.6% (95% confidence interval (CI): 26.5-26.8) (men 22.4%, women 30.5%). The most common locations were knee (13.8%), hip (5.8%) and hand (3.1%). Of the prevalent cases 26.8% had OA in multiple joints. By the year 2032, the proportion of the population aged ≥45 with doctor-diagnosed OA is estimated to increase from 26.6% to 29.5% (any location), from 13.8% to 15.7% for the knee and 5.8-6.9% for the hip. CONCLUSION: In 2032, at least an additional 26,000 individuals per 1 million population aged ≥45 years are estimated to have consulted a physician for OA in a peripheral joint compared to 2012. These findings underscore the need to address modifiable risk factors and develop new effective OA treatments.

Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis.

AIM: Duodenal adenomatosis in familial adenomatous polyposis results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study was to present the results of long-term duodenal surveillance and to evaluate the risk of cancer development. METHOD: Follow up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included the χ(2) test, actuarial method and Kaplan-Meier analysis. RESULTS: Among 304 patients, 261 (86%) had more than one endoscopy. The median follow up was 14 (interquartile range, 9-17) years. The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI, 84-93), and of Spigelman stage IV was 35% (95% CI, 25-45). The Spigelman stage improved in 32 (12%) patients, remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty (7%) patients had duodenal cancer at a median age of 56 (range, 44-82) years. The cumulative cancer incidence was 18% at 75 years of age (95% CI, 8-28) and increased with increasing Spigelman stage at the index endoscopy to 33% in Spigelman stage IV (P < 0.0001). The median overall survival was 6.4 years (95% CI, 1.7 to not estimated): 8 years after a screen-detected cancer vs 0.8 years (95% CI, 0.03-1.7) after a symptomatic cancer (P < 0.0001). The location of the mutation in the APC gene did not influence the risk of developing Spigelman stage IV (P = 0.46) or duodenal cancer (P = 0.83). CONCLUSION: The risk of duodenal cancer in familial adenomatous polyposis is considerable, and regular surveillance and cancer prophylactic surgery result in a significantly improved prognosis.

Usefulness of colonoscopic examination with indigo carmine in diagnosing microscopic colitis.

Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is epitomized by chronic watery diarrhea, endoscopically normal colonic mucosa, and characteristic histopathological features. Reports on chromoendoscopic findings in microscopic colitis are scarce and in this paper we describe such findings. We have examined 13 patients with microscopic colitis by means of chromoendoscopy with indigo carmine 0.2 % - 0.5 %. In all 13 cases continuous mucosal changes were seen, with disappearance of innominate grooves or with irregularity of grooves. The segmental distribution of abnormal chromoendoscopic findings corresponded almost completely with the microscopic features. A diffuse mosaic pattern was found in five of 10 cases of collagenous colitis and in all three cases of lymphocytic colitis. Uneven surface was seen in four cases of collagenous colitis, one of collagenous colitis in remission, and one of lymphocytic colitis, and a nodular surface was recorded in five cases of collagenous colitis but in none of the lymphocytic colitis cases. If these findings can be reproduced in larger series of microscopic colitis cases, the need for biopsies as a diagnostic tool might be restricted to patients where chromoendoscopy shows clear mucosal changes, thereby saving costs and limiting possible complications associated with multiple biopsies.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Health-related quality of life in diabetic patients with carpal tunnel syndrome.

AIMS: To determine health-related quality of life (HRQL) in diabetic and non-diabetic patients with carpal tunnel syndrome (CTS) before and after surgical treatment. METHODS: In a prospective study, 35 consecutive diabetic patients with CTS were age and gender matched with 31 non-diabetic patients with idiopathic CTS. At baseline (preoperatively), 6, 12 and 52 weeks after surgical carpal tunnel release, patients completed the generic Short-Form 36 (SF-36) and the disease-specific Boston Carpal Tunnel Questionnaire (BCTQ). RESULTS: The SF-36 physical component scores at baseline were significantly reduced for diabetic (39+/-7.4) compared with non-diabetic patients (48+/-9.0) (P<0.05). Mixed model analysis demonstrated no differences in post-surgical improvement over time between diabetic and non-diabetic patients. The largest clinical effect was found for bodily pain (effect size 0.8). However, population norms were not reached for the diabetic patients. At baseline, no difference was found in mental component score, which deteriorated over time for diabetic patients. At baseline, BCTQ demonstrated that diabetic patients experienced more pronounced 'numbness in the hand' than non-diabetic patients. Large clinical improvements were found in both symptom severity (effect size 1.98-2.14) and functional status score (effect size 0.89-0.94) for both diabetic and non-diabetic patients, with no difference between the two patient groups. CONCLUSIONS: HRQL is impaired in diabetic patients with CTS compared with non-diabetic patients with CTS and population norms. However, diabetic patients experience similar symptomatic and functional benefits from carpal tunnel release as do non-diabetic patients.

Does gold concentration in the blood influence the result of patch testing to gold?

BACKGROUND: We have recently found a correlation between contact allergy to gold sodium thiosulphate (GSTS) and gold concentration in the blood (B-Au) in a stented population: the higher the B-Au, the stronger the patch-test reaction. OBJECTIVES: To further investigate the correlation between B-Au and patch-test reactivity to gold. METHODS: In this provocation control cross-over trial of 24 patients with dermatitis with a known contact allergy to gold, the patients were randomized into two groups where one was topically provoked to gold (15 mg GSTS) and one to the control. All patients were simultaneously patch tested with GSTS in 10 aqueous dilutions (1.1 mg GSTS). Patch-test readings were performed and blood was drawn. After 6 weeks, the experiment was repeated and the group that had previously been provoked with gold was now provoked with the control and vice versa. RESULTS: B-Au was higher after gold provocation whereas no treatment effect was discerned for minimal eliciting concentration (MEC) or summarized test score (STS). Instead, significant differences in period effect were observed implying higher B-Au and STS and lower MEC on test occasion II. The most likely explanation is the increased B-Au and /or booster effect from test occasion I. There was a correlation between B-Au and MEC: the higher the B-Au, the lower the MEC. CONCLUSIONS: The correlation between B-Au and MEC indicates that the B-Au is of importance for the skin reactivity to gold.

Is contact allergy to disperse dyes and related substances associated with textile dermatitis?

BACKGROUND: Disperse dyes (DDs) are the most common sensitizers among textile dyes, but there is little knowledge of the clinical relevance of positive patch test reactions. OBJECTIVE: To investigate if patient-reported textile-related skin problems can be explained by contact allergy to eight different DDs and/or to chemically related substances, by occupation or by atopic constitution, and if the skin problems are influenced by age or sex. METHODS: A questionnaire on textile-related skin problems was answered by 858 of 982 consecutively patch tested patients in Malmö, Sweden and in Leuven, Belgium. The baseline series used for patch testing was supplemented with a textile dye mix (TDM) consisting of the eight DDs and with the separate dyes. The association between textile-related skin problems and contact allergy to the DDs and other risk factors was investigated using multiple logistic regression analysis. RESULTS: Eighteen per cent of the patients suspected textiles as a cause of their skin problems. Atopic constitution and female sex were risk factors for skin reactions. Synthetic materials were the most common textiles to give skin problems. A significant association was found between self-reported textile-related skin problems and contact allergy to para-phenylenediamine (PPD) [adjusted odds ratio (OR) 2.1; 95% confidence interval (CI) 1.0-4.3]. A similar, but more imprecise, adjusted OR was found for TDM (OR 1.9; 95% CI 0.57-5.6). Contact allergy to black rubber mix was too rare to be evaluated. CONCLUSIONS: Contact allergy to PPD was a more prevalent indicator for skin reactions to textiles than the TDM used in this study.

Density functional theory based screening of ternary alkali-transition metal borohydrides: a computational material design project.

We present a computational screening study of ternary metal borohydrides for reversible hydrogen storage based on density functional theory. We investigate the stability and decomposition of alloys containing 1 alkali metal atom, Li, Na, or K (M(1)); and 1 alkali, alkaline earth or 3d/4d transition metal atom (M(2)) plus two to five (BH(4))(-) groups, i.e., M(1)M(2)(BH(4))(2-5), using a number of model structures with trigonal, tetrahedral, octahedral, and free coordination of the metal borohydride complexes. Of the over 700 investigated structures, about 20 were predicted to form potentially stable alloys with promising decomposition energies. The M(1)(Al/Mn/Fe)(BH(4))(4), (Li/Na)Zn(BH(4))(3), and (Na/K)(Ni/Co)(BH(4))(3) alloys are found to be the most promising, followed by selected M(1)(Nb/Rh)(BH(4))(4) alloys.

Minimizing contrast medium doses to diagnose pulmonary embolism with 80-kVp multidetector computed tomography in azotemic patients.

BACKGROUND: In diagnosing acute pulmonary embolism (PE) in azotemic patients, scintigraphy and magnetic resonance imaging are frequently inconclusive or not available in many hospitals. Computed tomography is readily available, but relatively high doses (30-50 g I) of potentially nephrotoxic iodine contrast media (CM) are used. PURPOSE: To report on the diagnostic quality and possible contrast-induced nephropathy (CIN) after substantially reduced CM doses to diagnose PE in azotemic patients using 80-peak kilovoltage (kVp) 16-row multidetector computed tomography (MDCT) combined with CM doses tailored to body weight, fixed injection duration adapted to scan time, automatic bolus tracking, and saline chaser. MATERIAL AND METHODS: Patients with estimated glomerular filtration rate (eGFR) <50 ml/min were scheduled to undergo 80-kVp MDCT using 200 mg I/kg, and those with eGFR >or=50 ml/min, 120-kVp MDCT with 320 mg I/kg. Both protocols used an 80-kg maximum dose weight and a fixed 15-s injection time. Pulmonary artery density and contrast-to-noise ratio were measured assuming 70 Hounsfield units (HU) for a fresh clot. CIN was defined as a plasma creatinine rise >44.2 micromol/l from baseline. RESULTS: 89/148 patients (63/68 females) underwent 80-/120-kVp protocols, respectively, with 95% of the examinations being subjectively excellent or adequate. Mean values in the 80-/120-kVp cohorts regarding age were 82/65 years, body weight 66/78 kg, effective mAs 277/117, CM dose 13/23 g I, pulmonary artery density 359/345 HU, image noise (1 standard deviation) 24/21 HU, contrast-to-noise ratio 13/13, and dose-length product 173/258 mGy x cm. Only 1/65 and 2/119 patients in the 80- and 120-kVp cohorts, respectively, with negative CT and no anticoagulation suffered non-fatal thromboembolism during 3-month follow-up. No patient developed CIN. CONCLUSION: 80-kVp 16-row MDCT with optimization of injection parameters may be performed with preserved diagnostic quality, using markedly reduced CM doses compared with common routine practice, which should be to the benefit of patients at risk of CIN.

Contrast medium dose-to-GFR ratio: a measure of systemic exposure to predict contrast-induced nephropathy after percutaneous coronary intervention.

BACKGROUND: The contrast medium (CM) dose-to-eGFR (estimated glomerular filtration rate) ratio has recently been advocated to express systemic exposure to CM in assessing the risk of contrast medium-induced nephropathy (CIN). PURPOSE: To evaluate how CIN risk might vary with decreasing eGFR at fixed CM-dose/eGFR ratios and other CIN risk factors, and to find a relatively safe CM-dose/eGFR ratio. MATERIAL AND METHODS: 391 patients underwent primary coronary angioplasty for ST-segment elevation acute myocardial infarction. CM dose (grams iodine; g I), eGFR (ml/min), and preprocedural CIN risk factors were entered into a multiple logistic regression model. From the established statistical model, the probability of CIN (>or=44.2 micromol/l serum creatinine rise or oliguria/anuria) was calculated at various eGFR levels based on g-I/eGFR ratios of 1:2, 1:1, 2:1, and 3:1. RESULTS: At a g-I/eGFR ratio <1 the risk of CIN was 3%, while it was 25% at a g-I/eGFR ratio >or=1. Independent predictors of CIN were CM dose, eGFR, left ventricular ejection fraction (LVEF) and cardiogenic shock (ROC area =0.87). An estimated CIN risk of 10% would for example occur at a g-I/eGFR ratio of 1.5:1 in patients with 50% LVEF without shock. At a 1:2, 1:1, 2:1, and 3:1 g-I/eGFR ratio with 50% LVEF without shock, the CIN risk was about 2, 6, 18, and 30%, respectively, over a wide range of eGFR values (30-90 ml/min). At a 1:1 g-I/eGFR ratio with 50% LVEF+shock, 25% LVEF without shock, or 25% LVEF+shock, the CIN risk was 20, 55, and 80%, respectively. CONCLUSION: Relating CM dose to eGFR appears to be an attractive pharmacotoxic model to assess CIN risk. At fixed CM-dose/eGFR ratios, CIN risk increased marginally with decreasing eGFR. Limiting the CM dose in g I numerically to the eGFR value in ml/min or less may be relatively safe with regard to CIN, unless multiple risk factors are present.

Validation of Random Sampling as an Estimation Procedure for Lyme Disease Surveillance in Massachusetts and Minnesota.

Many disease surveillance programs, including the Massachusetts Department of Public Health and the Minnesota Department of Health, are challenged by marked increases in Lyme disease (LD) reports. The purpose of this study was to retrospectively analyse LD reports from 2005 through 2012 to determine whether key epidemiologic characteristics were statistically indistinguishable when an estimation procedure based on sampling was utilized. Estimates of the number of LD cases were produced by taking random 20% and 50% samples of laboratory-only reports, multiplying by 5 or 2, respectively, and adding the number of provider-reported confirmed cases. Estimated LD case counts were compared to observed, confirmed cases each year. In addition, the proportions of cases that were male, were ≤12 years of age, had erythema migrans (EM), had any late manifestation of LD, had a specific late manifestation of LD (arthritis, cranial neuritis or carditis) or lived in a specific region were compared to the proportions of cases identified using standard surveillance to determine whether estimated proportions were representative of observed proportions. Results indicate that the estimated counts of confirmed LD cases were consistently similar to observed, confirmed LD cases and accurately conveyed temporal trends. Most of the key demographic and disease manifestation characteristics were not significantly different (P < 0.05), although estimates for the 20% random sample demonstrated greater deviation than the 50% random sample. Applying this estimation procedure in endemic states could conserve limited resources by reducing follow-up effort while maintaining the ability to track disease trends.

Adolescent neurocognitive development and impacts of substance use: Overview of the adolescent brain cognitive development (ABCD) baseline neurocognition battery.

Adolescence is characterized by numerous social, hormonal and physical changes, as well as a marked increase in risk-taking behaviors. Dual systems models attribute adolescent risk-taking to tensions between developing capacities for cognitive control and motivational strivings, which may peak at this time. A comprehensive understanding of neurocognitive development during the adolescent period is necessary to permit the distinction between premorbid vulnerabilities and consequences of behaviors such as substance use. Thus, the prospective assessment of cognitive development is fundamental to the aims of the newly launched Adolescent Brain and Cognitive Development (ABCD) Consortium. This paper details the rationale for ABC'lected measures of neurocognition, presents preliminary descriptive data on an initial sample of 2299 participants, and provides a context for how this large-scale project can inform our understanding of adolescent neurodevelopment.