Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing’s syndrome, because there is no recent consensus on ...the management of this rare disorder.
Participants: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing’s syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing’s disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing’s disease, and 5) management of ectopic ACTH syndrome, Nelson’s syndrome, and special patient populations.
Evidence: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking.
Consensus Process: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority.
Conclusions: ACTH-dependent Cushing’s syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing’s syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing’s disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing’s syndrome, early diagnosis and prompt therapy are warranted.
We combined two existing datasets of vegetation aboveground biomass (AGB) (Proceedings of the National Academy of Sciences of the United States of America, 108, 2011, 9899; Nature Climate Change, 2, ...2012, 182) into a pan‐tropical AGB map at 1‐km resolution using an independent reference dataset of field observations and locally calibrated high‐resolution biomass maps, harmonized and upscaled to 14 477 1‐km AGB estimates. Our data fusion approach uses bias removal and weighted linear averaging that incorporates and spatializes the biomass patterns indicated by the reference data. The method was applied independently in areas (strata) with homogeneous error patterns of the input (Saatchi and Baccini) maps, which were estimated from the reference data and additional covariates. Based on the fused map, we estimated AGB stock for the tropics (23.4 N–23.4 S) of 375 Pg dry mass, 9–18% lower than the Saatchi and Baccini estimates. The fused map also showed differing spatial patterns of AGB over large areas, with higher AGB density in the dense forest areas in the Congo basin, Eastern Amazon and South‐East Asia, and lower values in Central America and in most dry vegetation areas of Africa than either of the input maps. The validation exercise, based on 2118 estimates from the reference dataset not used in the fusion process, showed that the fused map had a RMSE 15–21% lower than that of the input maps and, most importantly, nearly unbiased estimates (mean bias 5 Mg dry mass ha⁻¹ vs. 21 and 28 Mg ha⁻¹ for the input maps). The fusion method can be applied at any scale including the policy‐relevant national level, where it can provide improved biomass estimates by integrating existing regional biomass maps as input maps and additional, country‐specific reference datasets.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This analysis involving patients with stage III colon cancer pooled the findings of six clinical trials regarding the effect of adjuvant-therapy duration on disease-free survival. The results varied ...according to drug regimen and disease subgroup.
Background
Stroke risk is increased during pregnancy, but estimates of pregnancy-related stroke incidence vary widely.
Aims
A systematic review and meta-analysis was conducted to assess the incidence ...of stroke during pregnancy and the puerperium. Ovid Medline, EMBASE, and ISI Web of Science were searched for studies published between 1990 and January 2017 reporting stroke incidence during pregnancy and postpartum, from defined pregnancy populations. Pooled analyses were conducted using a random effects approach and expressed as an incidence rate per 100,000 pregnancies, with 95% confidence intervals. Subgroup analyses of stroke type and timing were conducted.
Summary of review
Eleven studies met inclusion criteria. Variation in estimated rates was noted based on geography and study methodology. The pooled crude rate of pregnancy-related stroke was 30.0 per 100,000 pregnancies (95% confidence interval 18.8–47.9). The pooled crude rates from nonhemorrhagic stroke (arterial and cerebral venous sinus thrombosis) were 19.9 (95% confidence interval 10.7–36.9) and from hemorrhage 12.2 (95% confidence interval 6.4–23.2) per 100,000 pregnancies. For studies separately reporting cerebral venous sinus thrombosis, the rates were roughly equal between ischemic stroke (12.2, 95% confidence interval 6.7–22.2), cerebral venous sinus thrombosis (9.1, 95% confidence interval 4.3–18.9), and hemorrhage (12.2, 95% confidence interval 6.4–23.2). The crude stroke rate for antenatal/perinatal stroke was 18.3 (95% confidence interval 11.9–28.2), and for postpartum stroke was 14.7 (95% confidence interval 8.3–26.1).
Conclusions
Stroke affects 30.0 per 100,000 pregnancies, with ischemia, cerebral venous sinus thrombosis, and hemorrhage causing roughly equal numbers and with highest risk peripartum and postpartum. Organized approaches to the management of this high-risk population, informed by existing evidence from stroke and obstetrical care are needed.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Aims/hypothesis
The aim of this study was to examine the prevalence of and risk factors for diabetic retinopathy in people with newly diagnosed type 2 diabetes mellitus, using Scottish national data.
...Methods
We identified individuals diagnosed with type 2 diabetes mellitus in Scotland between January 2005 and May 2008 using data from the national diabetes database. We calculated the prevalence of retinopathy and ORs for risk factors associated with retinopathy at first screening.
Results
Of the 51,526 people with newly diagnosed type 2 diabetes mellitus identified, 91.4% had been screened by 31 December 2010. The median time to first screening was 315 days (interquartile range IQR 111–607 days), but by 2008 the median was 83 days (IQR 51–135 days). The prevalence at first screening of any retinopathy was 19.3%, and for referable retinopathy it was 1.9%. For individuals screened after a year the prevalence of any retinopathy was 20.5% and referable retinopathy was 2.3%. Any retinopathy at screening was associated with male sex (OR 1.19, 95% CI 1.14, 1.25), HbA
1c
(OR 1.07, 95% CI 1.06, 1.08 per 1% 11 mmol/mol increase), systolic BP (OR 1.06, 95% CI 1.05, 1.08 per 10 mmHg increase), time to screening (OR for screening >1 year post diagnosis = 1.12, 95% CI 1.07, 1.17) and obesity (OR 0.87, 95% CI 0.82, 0.93) in multivariate analysis.
Conclusions/interpretation
The prevalence of retinopathy at first screening is lower than in previous UK studies, consistent with earlier diagnosis of diabetes. Most newly diagnosed type 2 diabetic patients in Scotland are screened within an acceptable interval and the prevalence of referable disease is low, even in those with delayed screening.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Degenerative cervical myelopathy DCM is a disabling and increasingly prevalent group of diseases. Heterogeneous reporting of trial outcomes limits effective inter-study comparison and optimisation of ...treatment. This is recognised in many fields of healthcare research. The present study aims to assess the heterogeneity of outcome reporting in DCM as the premise for the development of a standardised reporting set.
A systematic review of MEDLINE and EMBASE databases, registered with PROSPERO (CRD42015025497) was conducted in accordance with PRISMA guidelines. Full text articles in English, with >50 patients (prospective) or >200 patients (retrospective), reporting outcomes of DCM were eligible.
108 studies, assessing 23,876 patients, conducted world-wide, were identified. Reported outcome themes included function (reported by 97, 90% of studies), complications (reported by 56, 52% of studies), quality of life (reported by 31, 29% of studies), pain (reported by 29, 27% of studies) and imaging (reported by 59, 55% of studies). Only 7 (6%) studies considered all of domains in a single publication. All domains showed variability in reporting.
Significant heterogeneity exists in the reporting of outcomes in DCM. The development of a consensus minimum dataset will facilitate future research synthesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Desert dust perturbs climate by directly and indirectly interacting with incoming solar and outgoing long wave radiation, thereby changing precipitation and temperature, in addition to modifying ...ocean and land biogeochemistry. While we know that desert dust is sensitive to perturbations in climate and human land use, previous studies have been unable to determine whether humans were increasing or decreasing desert dust in the global average. Here we present observational estimates of desert dust based on paleodata proxies showing a doubling of desert dust during the 20th century over much, but not all the globe. Large uncertainties remain in estimates of desert dust variability over 20th century due to limited data. Using these observational estimates of desert dust change in combination with ocean, atmosphere and land models, we calculate the net radiative effect of these observed changes (top of atmosphere) over the 20th century to be −0.14 ± 0.11 W/m2 (1990–1999 vs. 1905–1914). The estimated radiative change due to dust is especially strong between the heavily loaded 1980–1989 and the less heavily loaded 1955–1964 time periods (−0.57 ± 0.46 W/m2), which model simulations suggest may have reduced the rate of temperature increase between these time periods by 0.11 °C. Model simulations also indicate strong regional shifts in precipitation and temperature from desert dust changes, causing 6 ppm (12 PgC) reduction in model carbon uptake by the terrestrial biosphere over the 20th century. Desert dust carries iron, an important micronutrient for ocean biogeochemistry that can modulate ocean carbon storage; here we show that dust deposition trends increase ocean productivity by an estimated 6% over the 20th century, drawing down an additional 4 ppm (8 PgC) of carbon dioxide into the oceans. Thus, perturbations to desert dust over the 20th century inferred from observations are potentially important for climate and biogeochemistry, and our understanding of these changes and their impacts should continue to be refined.
Sleep problems have a high prevalence and negative daytime consequences in adolescents. Current sleep measures for this age group have limitations. The Patient‐Reported Outcomes Measurement ...Information System (PROMIS®) developed sleep item banks for adults. In a previous validation study, these item banks were adapted to a shortened version for adolescents. The current study aimed to further explore the psychometric properties of the 11‐item Sleep‐Related Impairment and 23‐item Sleep Disturbance item banks in Dutch adolescents. We investigated structural validity by testing item response theory assumptions and model fit; measurement invariance by performing differential item functioning analyses; performance as a computerized adaptive test; reliability by marginal reliability estimates and test–retest reliability (intraclass correlation coefficients and limits of agreement); and construct validity by hypothesis testing. Additionally, we provide mean values for the item banks. The study sample consisted of 1,046 adolescents (mean age 14.3 ± 1.6), including 1,013 high‐school students and 33 sleep‐clinic patients. The Sleep Disturbance‐23 showed lack of unidimensionality, but had sufficient test–retest reliability, and could distinguish between adolescents with and without sleep or health issues. The Sleep‐Related Impairment‐11 showed sufficient unidimensionality and model fit and was thus tested as a computerized adaptive test, demonstrating an equal amount of reliable measures to the full item bank. Furthermore, the Sleep‐Related Impairment‐11 could distinguish between adolescents with and without sleep or health issues and test–retest reliability was moderate. The use of both item banks in the full form and the use of the Sleep‐related Impairment‐11 as a computer adaptive test is recommended.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In contrast to primary colorectal cancer (CRC) little is known about the genomic landscape of metastasized CRC. Here we present whole genome sequencing data of metastases of 429 CRC patients ...participating in the pan-cancer CPCT-02 study (NCT01855477). Unsupervised clustering using mutational signature patterns highlights three major patient groups characterized by signatures known from primary CRC, signatures associated with received prior treatments, and metastasis-specific signatures. Compared to primary CRC, we identify additional putative (non-coding) driver genes and increased frequencies in driver gene mutations. In addition, we identify specific genes preferentially affected by microsatellite instability. CRC-specific 1kb-10Mb deletions, enriched for common fragile sites, and LINC00672 mutations are associated with response to treatment in general, whereas FBXW7 mutations predict poor response specifically to EGFR-targeted treatment. In conclusion, the genomic landscape of mCRC shows defined changes compared to primary CRC, is affected by prior treatments and contains features with potential clinical relevance.
Surveillance testing for infectious disease is an important tool to combat disease transmission at the population level. During the SARS-CoV-2 pandemic, RT-PCR tests have been considered the gold ...standard due to their high sensitivity and specificity. However, RT-PCR tests for SARS-CoV-2 have been shown to return positive results when performed to individuals who are past the infectious stage of the disease. Meanwhile, antigen-based tests are often treated as a less accurate substitute for RT-PCR, however, new evidence suggests they may better reflect infectiousness. Consequently, the two test types may each be most optimally deployed in different settings. Here, we present an epidemiological model with surveillance testing and coordinated isolation in two congregate living settings (a nursing home and a university dormitory system) that considers test metrics with respect to viral culture, a proxy for infectiousness. Simulations show that antigen-based surveillance testing coupled with isolation greatly reduces disease burden and carries a lower economic cost than RT-PCR-based strategies. Antigen and RT-PCR tests perform different functions toward the goal of reducing infectious disease burden and should be used accordingly.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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