Objective To develop and evaluate a method of estimating patient-specific risk for fetal loss by combining maternal characteristics with serum markers. Study Design Data were obtained on 36,014 women ...from the FaSTER trial. Separate likelihood ratios were estimated for significant maternal characteristics and serum markers. Patient-specific risk was calculated by multiplying the incidence of fetal loss by the likelihood ratios for each maternal characteristic and for different serum marker combinations. Results Three hundred eighteen women had fetal loss < 24 weeks (early) and 103 > 24 weeks (late). Clinical characteristics evaluated included maternal age, body mass index, race, parity, threatened abortion, previous preterm delivery, and previous early loss. Serum markers studied as possible predictors of early loss included first-trimester pregnancy-associated plasma protein A and second-trimester alpha-fetoprotein, and unconjugated estriol. A risk assessment for early loss based on all of these factors yielded a 46% detection rate, for a fixed 10% false-positive rate, 39% for 5% and 28% for 1%. The only significant marker for late loss was inhibin A. The detection rate was 27% for a fixed 10% false-positive rate and only increased slightly when clinical characteristics were added to the model. Conclusion Patient-specific risk assessment for early fetal loss using serum markers, with or without maternal characteristics, has a moderately high detection. Patient-specific risk assessment for late fetal loss has low detection rates.
Objective The purpose of this study was to calculate first and second trimester reference ranges and within-woman correlations for TSH, free T4, and thyroid antibodies. Study Design TSH, free T4, and ...thyroid antibodies were measured in paired sera from 9562 women in the FaSTER trial of Down syndrome screening. Results The median first trimester TSH (1.05 mIU/L) is lower than the second (1.23 mIU/L); and 98th centile is higher (4.15 vs 3.77 mIU/L). Within-woman paired TSH correlations are moderately strong ( r2 = 0.64). Among women with first trimester TSH values above the 98th centile, second trimester values are over the 95th centile in 68%. Median first trimester free T4 values (1.10 ng/dL) are higher than second (1.01 ng/dL). Paired free T4 measurements correlate weakly ( r2 = 0.23). Among women with first trimester free T4 values below the 2nd centile, second trimester values are below the 5th centile in 32%. Antibody measurements correlate strongly between trimesters (thyroperoxidase r2 = 0.79, thyroglobulin r2 = 0.83). Conclusion TSH and free T4 measurements require gestation-specific reference ranges.
Pelvic floor dysfunction is a common and potentially complex condition. Imaging can complement physical examination by revealing clinically occult abnormalities and clarifying the nature of the ...pelvic floor defects present. Imaging can add value in preoperative management for patients with a complex clinical presentation, and in postoperative management of patients suspected to have recurrent pelvic floor dysfunction or a surgical complication. Imaging findings are only clinically relevant if the patient is symptomatic. Several imaging modalities have a potential role in evaluating patients; the choice of modality depends on the patient's symptoms, the clinical information desired, and the usefulness of the test. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions; they are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals, and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Abstract Although there is limited evidence that antepartum testing decreases the risk for fetal death in low-risk pregnancies, women with high-risk factors for stillbirth should undergo antenatal ...fetal surveillance. The strongest evidence supporting antepartum testing pertains to pregnancies complicated by intrauterine fetal growth restriction secondary to uteroplacental insufficiency. The main ultrasound-based modalities to determine fetal health are the biophysical profile, modified biophysical profile, and duplex Doppler velocimetry. In patients at risk for cardiovascular compromise, fetal echocardiography may also be indicated to ensure fetal well-being. Although no single antenatal test has been shown to be superior, all have high negative predictive values. Weekly or twice-weekly fetal testing has become the standard practice in high-risk pregnancies. The timing for the initiation of assessments of fetal well-being should be tailored on the basis of the risk for stillbirth and the likelihood of survival with intervention. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (the RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Objective The purpose of this study was to examine how closely hypothyroidism management in the general pregnancy population satisfies recently issued guidelines and to determine whether improvements ...are indicated. Study Design This was an observational study in which women at 5 recruitment centers in the first- and second-trimester evaluation of risk for aneuploidy trial allowed the use of sequentially obtained first- and second-trimester sera for additional research. Three hundred eighty-nine women had hypothyroidism by self-report. Thyroid-related measurements were performed on all samples between July 2004 and May 2005. Results Forty-three percent of the thyroid-stimulating hormone (TSH) values are at or above recently recommended guidelines in the first trimester (2.5 mU/L), as opposed to 33% of the values in the second trimester (3.0 mU/L). Twenty percent of the TSH values are at or above a less restrictive 98th percentile of normal in the first trimester, as opposed to 23% of the values in the second trimester. Mean TSH levels are higher in women with antibodies. Free thyroxine values are unremarkable. Conclusion Future strategies should focus on more effectively treating women with hypothyroidism who have persistently elevated TSH values.
Although overweight and obesity have been studied in relation to individual cardiometabolic diseases, their association with risk of cardiometabolic multimorbidity is poorly understood. Here we aimed ...to establish the risk of incident cardiometabolic multimorbidity (ie, at least two from: type 2 diabetes, coronary heart disease, and stroke) in adults who are overweight and obese compared with those who are a healthy weight.
We pooled individual-participant data for BMI and incident cardiometabolic multimorbidity from 16 prospective cohort studies from the USA and Europe. Participants included in the analyses were 35 years or older and had data available for BMI at baseline and for type 2 diabetes, coronary heart disease, and stroke at baseline and follow-up. We excluded participants with a diagnosis of diabetes, coronary heart disease, or stroke at or before study baseline. According to WHO recommendations, we classified BMI into categories of healthy (20·0–24·9 kg/m2), overweight (25·0–29·9 kg/m2), class I (mild) obesity (30·0–34·9 kg/m2), and class II and III (severe) obesity (≥35·0 kg/m2). We used an inclusive definition of underweight (<20 kg/m2) to achieve sufficient case numbers for analysis. The main outcome was cardiometabolic multimorbidity (ie, developing at least two from: type 2 diabetes, coronary heart disease, and stroke). Incident cardiometabolic multimorbidity was ascertained via resurvey or linkage to electronic medical records (including hospital admissions and death). We analysed data from each cohort separately using logistic regression and then pooled cohort-specific estimates using random-effects meta-analysis.
Participants were 120 813 adults (mean age 51·4 years, range 35–103; 71 445 women) who did not have diabetes, coronary heart disease, or stroke at study baseline (1973–2012). During a mean follow-up of 10·7 years (1995–2014), we identified 1627 cases of multimorbidity. After adjustment for sociodemographic and lifestyle factors, compared with individuals with a healthy weight, the risk of developing cardiometabolic multimorbidity in overweight individuals was twice as high (odds ratio OR 2·0, 95% CI 1·7–2·4; p<0·0001), almost five times higher for individuals with class I obesity (4·5, 3·5–5·8; p<0·0001), and almost 15 times higher for individuals with classes II and III obesity combined (14·5, 10·1–21·0; p<0·0001). This association was noted in men and women, young and old, and white and non-white participants, and was not dependent on the method of exposure assessment or outcome ascertainment. In analyses of different combinations of cardiometabolic conditions, odds ratios associated with classes II and III obesity were 2·2 (95% CI 1·9–2·6) for vascular disease only (coronary heart disease or stroke), 12·0 (8·1–17·9) for vascular disease followed by diabetes, 18·6 (16·6–20·9) for diabetes only, and 29·8 (21·7–40·8) for diabetes followed by vascular disease.
The risk of cardiometabolic multimorbidity increases as BMI increases; from double in overweight people to more than ten times in severely obese people compared with individuals with a healthy BMI. Our findings highlight the need for clinicians to actively screen for diabetes in overweight and obese patients with vascular disease, and pay increased attention to prevention of vascular disease in obese individuals with diabetes.
NordForsk, Medical Research Council, Cancer Research UK, Finnish Work Environment Fund, and Academy of Finland.
Socioeconomic disadvantage is a risk factor for many diseases. We characterised cascades of these conditions by using a data-driven approach to examine the association between socioeconomic status ...and temporal sequences in the development of 56 common diseases and health conditions.
In this multi-cohort study, we used data from two Finnish prospective cohort studies: the Health and Social Support study and the Finnish Public Sector study. Our pooled prospective primary analysis data comprised 109 246 Finnish adults aged 17–77 years at study entry. We captured socioeconomic status using area deprivation and education at baseline (1998–2013). Participants were followed up for health conditions diagnosed according to the WHO International Classification of Diseases until 2016 using linkage to national health records. We tested the generalisability of our findings with an independent UK cohort study—the Whitehall II study (9838 people, baseline in 1997, follow-up to 2017)—using a further socioeconomic status indicator, occupational position.
During 1 110 831 person-years at risk, we recorded 245 573 hospitalisations in the Finnish cohorts; the corresponding numbers in the UK study were 60 946 hospitalisations in 186 572 person-years. Across the three socioeconomic position indicators and after adjustment for lifestyle factors, compared with more advantaged groups, low socioeconomic status was associated with increased risk for 18 (32·1%) of the 56 conditions. 16 diseases formed a cascade of inter-related health conditions with a hazard ratio greater than 5. This sequence began with psychiatric disorders, substance abuse, and self-harm, which were associated with later liver and renal diseases, ischaemic heart disease, cerebral infarction, chronic obstructive bronchitis, lung cancer, and dementia.
Our findings highlight the importance of mental health and behavioural problems in setting in motion the development of a range of socioeconomically patterned physical illnesses. Policy and health-care practice addressing psychological health issues in social context and early in the life course could be effective strategies for reducing health inequalities.
UK Medical Research Council, US National Institute on Aging, NordForsk, British Heart Foundation, Academy of Finland, and Helsinki Institute of Life Science.
Background Neoadjuvant chemoradiotherapy followed by operative staging and liver transplantation is an effective treatment for patients with unresectable hilar cholangiocarcinoma (CCA) and CCA ...arising in the setting of primary sclerosing cholangitis (PSC). Pathologic confirmation of CCA is notoriously difficult, and many patients have been treated based on clinical criteria without pathological confirmation. Study Design We reviewed our experience with the specific aim of determining the need for pathological confirmation of CCA before treatment. Results Two hundred and fifteen patients received neoadjuvant therapy between 1992 and 2011. One hundred and eighty-two patients underwent operative staging and 38 (21%) had findings that precluded transplantation. Pathological confirmation of CCA before therapy was achieved in 45 of 87 (52%) PSC patients and 22 of 49 (45%) de novo patients who underwent transplantation. Pretreatment pathological confirmation was associated with significantly worse 5-year survival after start of therapy for PSC patients (50% vs 80%; p = 0.001), but not for de novo patients (39% vs 48%; p = 0.27). Pretreatment pathological confirmation was associated with worse 5-year survival after transplantation for PSC patients (66% vs 92%; p = 0.01), but not for de novo patients (63% vs 65%; p = 0.71). The difference in the PSC patients was not due to recurrent cancer. Absence of pretreatment pathological confirmation did not result in less detection of residual CCA in the explanted livers or in less recurrence after transplantation. Conclusions Rates of residual CCA in liver explants and recurrences after transplantation are comparable for patients with and without pretreatment pathological confirmation of CCA and attest to the accuracy of clinical diagnostic criteria. Pretreatment pathological confirmation of CCA is desirable but should not be a requirement for treatment.
Obesity increases the risk of several chronic diseases, but the extent to which the obesity-related loss of disease-free years varies by lifestyle category and across socioeconomic groups is unclear. ...We estimated the number of years free from major non-communicable diseases in adults who are overweight and obese, compared with those who are normal weight.
We pooled individual-level data on body-mass index (BMI) and non-communicable diseases from men and women with no initial evidence of these diseases in European cohort studies from the Individual-Participant-Data Meta-Analysis in Working Populations consortium. BMI was assessed at baseline (1991–2008) and non-communicable diseases (incident type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease) were ascertained via linkage to records from national health registries, repeated medical examinations, or self-report. Disease-free years from age 40 years to 75 years associated with underweight (BMI <18·5 kg/m2), overweight (≥25 kg/m2 to <30 kg/m2), and obesity (class I mild ≥30 kg/m2 to <35 kg/m2; class II–III severe ≥35 kg/m2) compared with normal weight (≥18·5 kg/m2 to <25 kg/m2) were estimated.
Of 137 503 participants from ten studies, we excluded 6973 owing to missing data and 10 349 with prevalent disease at baseline, resulting in an analytic sample of 120 181 participants. Of 47 127 men, 211 (0·4%) were underweight, 21 468 (45·6%) normal weight, 20 738 (44·0%) overweight, 3982 (8·4%) class I obese, and 728 (1·5%) class II–III obese. The corresponding numbers among the 73 054 women were 1493 (2·0%), 44 760 (61·3%), 19 553 (26·8%), 5670 (7·8%), and 1578 (2·2%), respectively. During 1 328 873 person-years at risk (mean follow-up 11·5 years range 6·3–18·6), 8159 men and 8100 women developed at least one non-communicable disease. Between 40 years and 75 years, the estimated number of disease-free years was 29·3 (95% CI 28·8–29·8) in normal-weight men and 29·4 (28·7–30·0) in normal-weight women. Compared with normal weight, the loss of disease-free years in men was 1·8 (95% CI −1·3 to 4·9) for underweight, 1·1 (0·7 to 1·5) for overweight, 3·9 (2·9 to 4·9) for class I obese, and 8·5 (7·1 to 9·8) for class II–III obese. The corresponding estimates for women were 0·0 (−1·4 to 1·4) for underweight, 1·1 (0·6 to 1·5) for overweight, 2·7 (1·5 to 3·9) for class I obese, and 7·3 (6·1 to 8·6) for class II–III obese. The loss of disease-free years associated with class II–III obesity varied between 7·1 and 10·0 years in subgroups of participants of different socioeconomic level, physical activity level, and smoking habit.
Mild obesity was associated with the loss of one in ten, and severe obesity the loss of one in four potential disease-free years during middle and later adulthood. This increasing loss of disease-free years as obesity becomes more severe occurred in both sexes, among smokers and non-smokers, the physically active and inactive, and across the socioeconomic hierarchy.
NordForsk, UK Medical Research Council, US National Institute on Aging, Academy of Finland, Helsinki Institute of Life Science, and Cancer Research UK.
Background Dural venous sinus thrombosis (DVST) is a cause of infarction and intracranial hemorrhage (ICH) that can lead to significant morbidity. Endovascular therapy has emerged as an adjunctive ...therapy in select cases but has been associated with increased hemorrhagic complications. We present our experience with a large single-center cohort of DVST cases treated with current-generation thrombectomy devices. Materials and Methods In this retrospective cohort study, a chart review was performed to compare presentations and outcomes of patients treated with anticoagulation alone with those treated with additional interventional therapy, using the modified Rankin Scale (mRS) score at discharge and at 90 days' follow-up. Results A total of 66 patients were included; 37 were treated with anticoagulation alone, and 29 underwent additional interventional therapy. Patients presenting with ICH or infarction had a significantly greater likelihood of disability at the time of discharge (odds ratio OR of 64.5 and 45.8, respectively; P < .0001) and at 90 days (OR of 28.4 and 22.8, respectively; P < .0001). Patients presenting with ICH or infarction were more likely to be selected for endovascular therapy ( P < .05). Endovascular therapy was typically performed within 24 hours of admission; 9 patients (31%) had post-treatment hemorrhage, with 2 being (6.9%) symptomatic. There were fewer patients with slight disability (mRS score ≤1) in the endovascular group compared with the anticoagulation group at discharge ( P = .05), but outcomes were not significantly different at 90 days ( P = .19). Conclusions Despite a higher rate of ICH or infarction at presentation in the endovascular group and an increased risk of postprocedural ICH, both treatment groups had similarly good functional outcomes at 90 days.
PDF
