Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Tyggegummi for å gjenopprette tarmfunksjon etter bukkirurgi. Kvalitetsforbedringsprosjekt

Postoperativ ileus er en vanlig selvbegrensende komplikasjon ved bukkirurgi. Noen pasienter får imidlertid en langvarig postoperativ ileus. Som konsekvens av dette risikerer disse pasientene å få flere komplikasjoner og sykehuset får økte kostnader. Derfor er det viktig å forebygge tilstanden. Noen internasjonale oppslagsverk anbefaler tyggegummi som forebyggende tiltak, men dette er ikke nevnt i norske retningslinjer. I dette kvalitetsforbedringsprosjektet undersøker vi kunnskapsgrunnlaget for tiltaket og hvordan dette kan implementeres i praksis på en sykehusavdeling i Norge. Kunnskapsgrunnlag For å undersøke kunnskapsgrunnlaget formulerte vi et PICO-spørsmål og søkte igjennom søkemotoren McMaster Plus på Helsebibliotekets nettsider. Vi fant to retningslinjer, i BMJ Best Practice og UpToDate, som begge anbefalte tyggegummi for å forkorte tid med postoperativ ileus. Kunnskapsgrunnlaget bedømmes av middels god kvalitet og det gis en svak anbefaling av begge oppslagsverkene. Studiene viser at tyggegummi reduserer liggetid på sykehus og tid til første avføring og luftavgang. Vår anbefaling av tiltaket baserer seg i stor grad på retningslinjen fra BMJ Best Practice fordi den tar for seg en Cochrane-oversikt fra 2015, og dermed en oppdatert anbefaling av tiltaket. Dagens praksis, tiltak og indikatorer Vi gikk videre med kunnskapsgrunnlaget til gastrokirurgisk sengepost på Drammen sykehus som fortalte at tyggegummi foreslås til pasienter postoperativt sporadisk. Deretter lagde vi en plan for implementering av rutinemessig utdeling av tyggegummi til pasienter som har blitt operert i buken. For å kunne måle kvaliteten på tiltaket formulerte vi kvalitetsindikatorer (tre strukturindikatorer): 1. Har avdelingen tyggegummi tilgjengelig? 2. Er informasjonen om effekt av tyggegummi for gjenopprettelse av tarmfunksjon etter abdominal kirurgi tilgjengelig for helsepersonell på avdelingen? 3. Er oppdatert pasientinformasjon tilgjengelig? Og én prosessindikator: 4. Tilbys det tyggegummi til pasienter? Ledelse og organisering Videre lagde vi en plan for gjennomføring av prosjektet. I grove trekk tenkte vi at operatør informerer om tiltaket, kartlegger kontraindikasjoner preoperativt og ordinerer tyggegummi på pasientkurven. Denne deles så ut av sykepleier. Målet med prosjektet er at alle pasienter uten kontraindikasjoner ved avdelingen tilbys tyggegummi tre ganger daglig under hele sitt postoperative opphold. De månedlige kostnadene ble beregnet til cirka 280kr. Vi undersøkte også mulige årsaker til vanskeligheter ved implementering av tiltaket og la vekt på aspekter ved ledelse som kan minske disse. Konklusjon Etter å ha undersøkt kunnskapsgrunnlaget og implementeringen av tiltaket i praksis kom vi fram til følgende konklusjon. Anbefalingene for bruk av tyggegummi postoperativt for å forebygge ileus er svake når man ser på kunnskapsgrunnlaget. Samtidig er tiltaket enkelt å implementere, billig, har potensielt stor effekt på pasientens helse og sykehusets økonomi. Tiltaket er i tillegg allerede implementert ved OUS, noe som bekrefter gjennomførbarheten av tiltaket. Vi konkluderer derfor med at tyggegummi bør tilbys til alle pasienter som er operert i buken og som ikke har kontraindikasjoner på gastrokirurgisk sengepost ved Drammen sykehus

Harmful effects of exercise intensity and exercise duration in patients with arrhythmogenic cardiomyopathy

Objectives The goal of this study was to explore the association between exercise duration versus exercise intensity and adverse outcome in patients with arrhythmogenic cardiomyopathy (AC). Background Vigorous exercise aggravates and accelerates AC, but there are no data assessing the harmful effects of exercise intensity and duration in these patients. Methods Exercise habits at time of diagnosis were recorded by standardized interviews in consecutive AC patients. Exercise >6 metabolic equivalents was defined as high intensity, and exercise duration was categorized as long if above median. Life-threatening ventricular arrhythmia (VA) was defined as aborted cardiac arrest, documented sustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter-defibrillator therapy. Results We included 173 AC patients (53% probands; 44% female; 41 ± 16 years of age). Median weekly exercise duration was 2.5 h (interquartile range: 2.0 to 5.5 h), and 91 patients (52%) reported high-intensity exercise. VA had occurred in 83 patients (48%) and was more prevalent in patients with high-intensity exercise than low-intensity exercise (74% vs. 20%, p < 0.001), and more prevalent in long-duration than short-duration exercise (65% vs. 31%, p < 0.001). High-intensity exercise was a strong and independent marker of VA, even when adjusted for the interaction with long-duration exercise (odds ratio: 3.8; 95% confidence interval: 1.3 to 11.0, p < 0.001), whereas long-duration exercise was not. Conclusions High-intensity exercise was a strong and independent marker of life-threatening VA in AC patients, independent of exercise duration. AC patients could be advised to restrict their exercise intensity

Prediction of Life-Threatening Ventricular Arrhythmia in Patients With Arrhythmogenic Cardiomyopathy: A Primary Prevention Cohort Study

Objectives: This study aimed to identify clinical, electrocardiographic (ECG) and cardiac imaging predictors of first-time life-threatening ventricular arrhythmia in patients with arrhythmogenic cardiomyopathy (AC). Background: The role of clinical, electrocardiographic, and cardiac imaging parameters in risk stratification of patients without ventricular arrhythmia is unclear. Methods: We followed consecutive AC probands and mutation-positive family members with no documented ventricular arrhythmia from time of diagnosis to first event. We assessed clinical, electrocardiographic, and cardiac imaging parameters according to Task Force Criteria of 2010 in addition to left ventricular (LV) and strain parameters. High-intensity exercise was defined as >6 metabolic equivalents. Results: We included 117 patients (29% probands, 50% female, age 40 ± 17 years). During 4.2 (interquartile range [IQR]: 2.4 to 7.4) years of follow-up, 18 (15%) patients experienced life-threatening ventricular arrhythmias. The 1-, 2-, and 5-year incidence was 6%, 9%, and 22%, respectively. History of high-intensity exercise, T-wave inversions ≥V3, and greater LV mechanical dispersion were the strongest risk markers (adjusted hazard ratio [HR]: 4.7 [95% confidence interval (CI): 1.2 to 17.5]; p = 0.02, 4.7 [95% CI: 1.6 to 13.9]; p = 0.005), and 1.4 [95% CI: 1.2 to 1.6] by 10-ms increments; p < 0.001, respectively). Median arrhythmia-free survival in patients with all risk factors was 1.2 (95% CI: 0.4 to 1.9) years, compared with an estimated 12.0 (95% CI: 11.5 to 12.5) years in patients without any risk factors. Conclusions: History of high-intensity exercise, electrocardiographic T-wave inversions ≥V3, and greater LV mechanical dispersion were strong predictors of life-threatening ventricular arrhythmia. Patients without any of these risk factors had minimal risk, whereas ≥2 risk factors increased the risk dramatically. This may help to make decisions on primary preventive implantable cardioverter defibrillator (ICD) therapy

Life-threatening arrhythmic presentation in patients with arrhythmogenic cardiomyopathy before and after entering the genomic era; a two-decade experience from a large volume center

Background: Arrhythmogenic cardiomyopathy (AC) is an inheritable progressive heart disease with high risk of life-threatening ventricular arrhythmia (VA). We aimed to explore the prevalence of VA as presenting event in patients with AC over two decades, symptoms preceding VA and compare the clinical presentations and rate of AC-diagnosis over time. Methods: We included consecutive AC-patients from our tertiary referral center. We recorded clinical history, VA (aborted cardiac arrest, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator therapy), cardiac symptoms preceding VA in AC, and compared the history of patients diagnosed before and after implementation of genetic testing. Results: We included 179 consecutive AC-patients and mutation-positive family members (95 [53%] probands, 84 [45%] female, 49 ± 17 years), 33 (18%) diagnosed before and 146 (82%) after genetic testing became available. VA led to the AC-diagnosis in 46 (26%), and was less prevalent after implementation of genetic testing (17[52%] vs. 29[20%], p < 0.001), also when adjusted for proband status (Adjusted OR 2.7, 95% CI 1.1–6.7, p = 0.03). Yearly rate of AC-diagnosis increased after implementation of genetic testing in probands (2.7 ± 1.3 vs. 6.8 ± 4.3, p = 0.01) and family members (0.7 ± 1.1 vs. 7.7 ± 5.9, p = 0.002). Most patients with VA (92%) reported cardiac symptoms prior to event, and exercise-induced syncope was the strongest marker of subsequent VA (Adjusted OR 5.3, 95% CI 1.7–16.4, p = 0.004). Conclusion: VA led to AC-diagnosis in 46% of probands and was preceded by cardiac symptoms in the majority of cases. Yearly rate of AC-diagnoses increased after the implementation of genetic testing and life-threatening presentation of AC-disease seemed to decrease

Left ventricular dysfunction in arrhythmogenic cardiomyopathy: Association with exercise exposure, genetic basis, and prognosis

Background Arrhythmogenic cardiomyopathy (AC) is characterized by biventricular dysfunction, exercise intolerance, and high risk of ventricular tachyarrhythmias and sudden death. Predisposing factors for left ventricular (LV) disease manifestation and its prognostic implication in AC are poorly described. We aimed to assess the associations of exercise exposure and genotype with LV dysfunction in AC, and to explore the impact of LV disease progression on adverse arrhythmic outcome. Methods and Results We included 168 patients with AC (50% probands, 45% women, 40±16 years old) with 715 echocardiographic exams (4.1±1.7 exams/patient, follow‐up 7.6 [interquartile range (IQR), 5.4–10.9] years) and complete exercise and genetic data in a longitudinal study. LV function by global longitudinal strain was −18.8% [IQR, −19.2% to −18.3%] at presentation and was worse in patients with greater exercise exposure (global longitudinal strain worsening, 0.09% [IQR, 0.01%–0.17%] per 5 MET‐hours/week, P=0.02). LV function by global longitudinal strain worsened, with 0.08% [IQR, 0.05%–0.12%] per year; (P<0.001), and progression was most evident in patients with desmoplakin genotype (P for interaction <0.001). Deterioration of LV function predicted incident ventricular tachyarrhythmia (aborted cardiac arrest, sustained ventricular tachycardia, or implantable cardioverter defibrillator shock) (adjusted odds ratio, 1.1 [IQR, 1.0–1.3] per 1% worsening by global longitudinal strain; P=0.02, adjusted for time and previous arrhythmic events). Conclusions Greater exercise exposure was associated with worse LV function at first visit of patients with AC but did not significantly affect the rate of LV progression during follow‐up. Progression of LV dysfunction was most pronounced in patients with desmoplakin genotypes. Deterioration of LV function during follow‐up predicted subsequent ventricular tachyarrhythmia and should be considered in risk stratification

Right Ventricular Functional Abnormalities in Arrhythmogenic Cardiomyopathy: Association With Life-Threatening Ventricular Arrhythmias

Objectives This study aimed to perform an external validation of the value of right ventricular (RV) deformation patterns and RV mechanical dispersion in patients with arrhythmogenic cardiomyopathy (AC). Secondly, this study assessed the association of these parameters with life-threatening ventricular arrhythmia (VA). Background Subtle RV dysfunction assessed by echocardiographic deformation imaging is valuable in AC diagnosis and risk prediction. Two different methods have emerged, the RV deformation pattern recognition and RV mechanical dispersion, but these have neither been externally validated nor compared. Methods We analyzed AC probands and mutation-positive family members, matched from 2 large European referral centers. We performed speckle tracking echocardiography, whereby we classified the subtricuspid deformation patterns from normal to abnormal and assessed RV mechanical dispersion from 6 segments. We defined VA as sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapy, or aborted cardiac arrest. Results We included 160 subjects, 80 from each center (43% proband, 55% women, age 41 ± 17 years). VA had occurred in 47 (29%) subjects. In both cohorts, patients with a history of VA showed abnormal deformation patterns (96% and 100%) and had greater RV mechanical dispersion (53 ± 30 ms vs. 30 ± 21 ms; p < 0.001 for the total cohort). Both parameters were independently associated to VA (adjusted odds ratio: 2.71 [95% confidence interval: 1.47 to 5.00] per class step-up, and 1.26 [95% confidence interval: 1.07 to 1.49]/10 ms, respectively). The association with VA significantly improved when adding RV mechanical dispersion to pattern recognition (net reclassification improvement 0.42; p = 0.02 and integrated diagnostic improvement 0.06; p = 0.01). Conclusions We externally validated 2 RV dysfunction parameters in AC. Adding RV mechanical dispersion to RV deformation patterns significantly improved the association with life-threatening VA, indicating incremental value

Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy

Abstract Aims We aimed to assess sex-specific phenotypes and disease progression, and their relation to exercise, in arrhythmogenic cardiomyopathy (AC) patients. Methods and results In this longitudinal cohort study, we included consecutive patients with AC from a referral centre. We performed echocardiography at baseline and repeatedly during follow-up. Patients’ exercise dose at inclusion was expressed as metabolic equivalents of task (MET)-h/week. Ventricular arrhythmia (VA) was defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by implantable cardioverter-defibrillator. We included 190 AC patients (45% female, 51% probands, age 41 ± 17 years). Ventricular arrhythmia had occurred at inclusion or occurred during follow-up in 85 patients (33% of females vs. 55% of males, P = 0.002). Exercise doses were higher in males compared with females [25 (interquartile range, IQR 14–51) vs. 12 (IQR 7–22) MET-h/week, P &amp;lt; 0.001]. Male sex was a marker of proband status [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4–5.0, P = 0.003] and a marker of VA (OR 2.6, 95% CI 1.4–5.0, P = 0.003), but not when adjusted for exercise dose and age (adjusted OR 1.8, 95% CI 0.9–3.6, P = 0.12 and 1.5, 95% CI 0.7–3.1, P = 0.30, by 5 MET-h/week increments). In all, 167 (88%) patients had ≥2 echocardiographic examinations during 6.9 (IQR 4.7–9.8) years of follow-up. We observed no sex differences in deterioration of right or left ventricular dimensions and functions. Conclusion Male AC patients were more often probands and had higher prevalence of VA than female patients, but not when adjusting for exercise dose. Importantly, disease progression was similar between male and female patients

Complications of implantable cardioverter-defibrillator treatment in arrhythmogenic right ventricular cardiomyopathy

Aims: Treatment with implantable cardioverter-defibrillators (ICD) is a cornerstone for prevention of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at describing the complications associated with ICD treatment in a multinational cohort with long-term follow-up. Methods and results: The Nordic ARVC registry was established in 2010 and encompasses a large multinational cohort of ARVC patients, including their clinical characteristics, treatment, and events during follow-up. We included 299 patients (66% males, median age 41 years). During a median follow-up of 10.6 years, 124 (41%) patients experienced appropriate ICD shock therapy, 28 (9%) experienced inappropriate shocks, 82 (27%) had a complication requiring surgery (mainly lead-related, n = 75), and 99 (33%) patients experienced the combined endpoint of either an inappropriate shock or a surgical complication. The crude rate of first inappropriate shock was 3.4% during the first year after implantation but decreased after the first year and plateaued over time. Contrary, the risk of a complication requiring surgery was 5.5% the first year and remained high throughout the study period. The combined risk of any complication was 7.9% the first year. In multivariate cox regression, presence of atrial fibrillation/flutter was a risk factor for inappropriate shock (P 0.05). Conclusion: Forty-one percent of ARVC patients treated with ICD experienced potentially life-saving ICD therapy during long-term follow-up. A third of the patients experienced a complication during follow-up with lead-related complications constituting the vast majority

Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. Objectives: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. Methods: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age &lt;30 years, 30 to 50 years, and =50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework. Results: We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up. Conclusions: Disease progression was similar in all age groups, and sustained VA also occurred in patients aged &gt;50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age