Abstract
Background
We evaluated the risk of pelvic inflammatory disease (PID), ectopic pregnancy, and infertility in women with a previous Chlamydia trachomatis (CT) diagnosis compared with women ...who tested negative for CT and CT untested women, considering both targeted and incidental (ie, prescribed for another indication) use of CT-effective antibiotics.
Methods
This was a retrospective study of women aged 12–25 years at start of follow-up within the Clinical Practice Research Datalink GOLD database linked to index of multiple deprivation quintiles, 2000–2013. CT test status and antibiotic use were determined in a time-dependent manner. Risk of PID, ectopic pregnancy, or female infertility were evaluated using of Cox proportional hazard models.
Results
We studied 857 324 women, contributing 6 457 060 person-years. Compared with women who tested CT-negative, women who tested CT-positive had an increased risk of PID (adjusted hazard ratio aHR, 2.36; 95% confidence interval CI, 2.01–2.79), ectopic pregnancy (aHR, 1.87; 95% CI, 1.38–2.54), and infertility (aHR, 1.85; 95% CI, 1.27–2.68). The PID risk was higher for women with 2 or more positive CT tests than those with 1 positive test. PID risk increased with the number of previous antibiotic prescriptions, regardless of CT test status.
Conclusions
We showed an association between CT-positive tests and 3 adverse reproductive health outcomes. Moreover, this risk increased with repeat CT infections. CT-effective antibiotic use showed no decreased risks of subsequent PID regardless of CT history. Our results confirm the reproductive health burden of CT, which requires adequate public health interventions.
Time-dependent analyses on a dataset including 6.5 million person-years confirms a strong relationship between Chlamydia trachomatis (CT) and pelvic inflammatory disease (PID), ectopic pregnancy, and female infertility. CT-effective antibiotic use showed no decreased PID risk in CT untested women.
Summary
Impaired physical performance is associated with increased fracture risk. Performance on four physical functioning tests and prevalence of sarcopenia were assessed for 1789 fracture patients ...and compared to reference data. Performance was low on all tests, especially for patients with a hip, major or ≥ 1 prevalent vertebral fracture.
Purpose Introduction
Impaired physical performance and sarcopenia are associated with increased fracture risk. This study aims to assess physical performance and the prevalence of sarcopenia in patients with a recent clinical fracture attending the Fracture Liaison Service (FLS) compared to population means.
Methods
In this cross-sectional study, chair stand test (CST), handgrip strength (HGS), timed-up-and-go (TUG), 6-min walking-test (6MWT), and sarcopenia (following EWGSOP2) were assessed. The proportion of patients with impaired/poor performance compared to reference data was calculated (Z-score: ≥ − 2SD to < − 1 (impaired) and < − 2 SD (poor)). Associations of fracture type, sex, age, and time since fracture with Z-scores were assessed using linear regression analyses.
Results
A total of 1789 consecutive FLS patients were included (median age (IQR): 66 (59–74), 70.7% females, 3.9 (± 1.6) months after fracture). The prevalence of impaired/poor performance for CST, HGS, TUG, and 6MWT was 39.2%, 30.4%, 21.9%, and 71.5%, respectively (expected proportion of 16%) and 2.8% had sarcopenia. Lower Z-scores (
P
< 0.001) were found for hip, major, and ≥ 1 prevalent vertebral fracture (VF) in CST (major: regression coefficient (
B
) (95%CI) = − 0.25 − 0.34, − 0.16; hip:
B
= − 0.32 − 0.47, − 0.17, VF:
B
= − 0.22 − 0.34, − 0.11), TUG; (major:
B
= − 0.54 − 0.75, − 0.33; hip:
B
= − 1.72 − 2.08, -1.35, VF:
B
= − 0.61 − 0.88, − 0.57), 6MWT (major:
B
= − 0.34 − 0.47, − 0.21; hip:
B
= − 0.99 − 1,22, − 0.77, VF:
B
= − 0.36 − 0.53, − 0.19).
Conclusions
Physical performance is significantly lower in FLS patients compared to healthy peers, especially in patients with hip, major or prevalent VF. These findings underline the need to assess and improve the physical performance of FLS patients, despite a low prevalence of sarcopenia.
Industrial penicillin production with the filamentous fungus Penicillium chrysogenum is based on an unprecedented effort in microbial strain improvement. To gain more insight into penicillin ...synthesis, we sequenced the 32.19 Mb genome of P. chrysogenum Wisconsin54-1255 and identified numerous genes responsible for key steps in penicillin production. DNA microarrays were used to compare the transcriptomes of the sequenced strain and a penicillinG high-producing strain, grown in the presence and absence of the side-chain precursor phenylacetic acid. Transcription of genes involved in biosynthesis of valine, cysteine and alpha-aminoadipic acid-precursors for penicillin biosynthesis-as well as of genes encoding microbody proteins, was increased in the high-producing strain. Some gene products were shown to be directly controlling beta-lactam output. Many key cellular transport processes involving penicillins and intermediates remain to be characterized at the molecular level. Genes predicted to encode transporters were strongly overrepresented among the genes transcriptionally upregulated under conditions that stimulate penicillinG production, illustrating potential for future genomics-driven metabolic engineering.
BACKGROUND Pre-eclampsia has a clear familial component, suggesting that the condition may be partly attributable to genetic susceptibility. The search for susceptibility genes has led to a drastic ...increase in the number of published studies associating genetic factors with pre-eclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis assessed the pooled effect of each genetic variant that is reproducibly associated with pre-eclampsia. METHODS Studies that assessed the association between genes and pre-eclampsia were searched in PubMed, Embase and Web of Science. We selected all genetic variants that were significantly associated with pre-eclampsia in an initial study and were subsequently independently reproduced in at least one additional study. All studies that assessed these reproduced variants were then included. The association between genetic variants and pre-eclampsia was calculated at the allele level, and the main measure of effect was a pooled odds ratio in a random-effects model. RESULTS The literature search yielded 2965 articles, of which 542 investigated genetic associations in pre-eclampsia. We identified 22 replicated genetic variants, of which 7 remained significantly associated with pre-eclampsia following meta-analysis. These variants were in or near the following genes: ACE, CTLA4, F2, FV, LPL and SERPINE1. CONCLUSIONS This meta-analysis identified seven genetic variants associated with pre-eclampsia. Importantly, many of these variants are also risk factors for developing cardiovascular disease, revealing that pre-eclampsia and cardiovascular disease have shared genetic risk factors. The contribution of the identified genetic variants in the pathogenesis of pre-eclampsia should be the focus of future studies.
Summary
In smokers and former smokers from the ECLIPSE cohort, there is an association between prevalent vertebral fractures (VFs) and coronary artery calcification (CAC). Chest CT scans provide the ...opportunity to evaluate VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions.
Introduction
Prevalence of VFs among smokers and patients with chronic obstructive pulmonary disease (COPD) is high, and an association between CAC and osteoporosis has been described. We investigated the associations between VFs and CAC (expressed in Agatston score) in (former) smokers.
Methods
Current and former smokers from the ECLIPSE study (designed to determine underlying COPD progression mechanisms) were studied. Baseline Agatston score (zero (0), medium (1–400), or high (> 400)), baseline bone attenuation (BA), and prevalent and incident VFs (vertebrae T
1
–L
1
) were assessed on CT.
Results
A total of 586 subjects were included (mean age 59.8 ± 8.3; 62.3% men; 70.1% with COPD; 21.0% with prevalent VFs; 196 with zero, 266 with medium, and 124 with high Agatston score). Of these, 23.4% suffered incident VFs within 3 years. In multivariate models, prevalent VFs were associated with medium (1.83 95% CI 1.01–3.30) and with high (OR = 3.06 1.45–6.47) Agatston score. After adjustment for BA, prevalent VFs were still associated with high (OR = 2.47 1.13–5.40), but not significantly with medium Agatston score (OR = 1.57 0.85–2.88). Similarly, after adjustment for BA, high (OR = 2.06 1.02–4.13) but not medium Agatston score (OR = 1.61 0.88–2.94) was associated with prevalent VFs. Agatston score at baseline was not associated with short-term VF incidence.
Conclusion
In (former) smokers, there was an association between prevalent VFs and Agatston score. Chest CT scans provide the opportunity to also evaluate for VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions.
Aims/hypothesis
Type 2 diabetes is a highly heterogeneous disease for which new subgroups (‘clusters’) have been proposed based on disease severity: moderate age-related diabetes (MARD), moderate ...obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD) and severe insulin-resistant diabetes (SIRD). It is unknown how disease severity is reflected in terms of quality of life in these clusters. Therefore, we aimed to investigate the cluster characteristics and cluster-wise evolution of quality of life in the previously defined clusters of type 2 diabetes.
Methods
We included individuals with type 2 diabetes from the Maastricht Study, who were allocated to clusters based on a nearest centroid approach. We used logistic regression to evaluate the cluster-wise association with diabetes-related complications. We plotted the evolution of HbA
1c
levels over time and used Kaplan–Meier curves and Cox regression to evaluate the cluster-wise time to reach adequate glycaemic control. Quality of life based on the Short Form 36 (SF-36) was also plotted over time and adjusted for age and sex using generalised estimating equations. The follow-up time was 7 years. Analyses were performed separately for people with newly diagnosed and already diagnosed type 2 diabetes.
Results
We included 127 newly diagnosed and 585 already diagnosed individuals. Already diagnosed people in the SIDD cluster were less likely to reach glycaemic control than people in the other clusters, with an HR compared with MARD of 0.31 (95% CI 0.22, 0.43). There were few differences in the mental component score of the SF-36 in both newly and already diagnosed individuals. In both groups, the MARD cluster had a higher physical component score of the SF-36 than the other clusters, and the MOD cluster scored similarly to the SIDD and SIRD clusters.
Conclusions/interpretation
Disease severity suggested by the clusters of type 2 diabetes is not entirely reflected in quality of life. In particular, the MOD cluster does not appear to be moderate in terms of quality of life. Use of the suggested cluster names in practice should be carefully considered, as the non-neutral nomenclature may affect disease perception in individuals with type 2 diabetes and their healthcare providers.
Graphical Abstract
Aim
To investigate the association between the use of incretin agents and the risk of pancreatic cancer.
Methods
A retrospective population‐based cohort study, using data from the Clinical Practice ...Research Datalink, 2007–2012, was conducted. Patients (n = 182 428) with at least one non‐insulin antidiabetic drug (NIAD) prescription and aged ≥18 years during data collection, were matched one‐to‐one to control patients without diabetes. Multivariable Cox proportional hazards models and a new user design were used to estimate the hazard ratio (HR) of pancreatic cancer in incretin users (n = 28 370) compared with control subjects without diabetes and other NIAD‐treated patients. Time‐dependent adjustments were made for age, sex, lifestyle, comorbidities and drug use.
Results
The mean duration of follow‐up was 4.1 years for incretin users. Current NIAD use was associated with a fourfold increased risk of pancreatic cancer HR 4.28, 95% confidence interval (CI) 3.49–5.24. This risk was almost doubled among current incretin users as compared with control subjects. Incretin use was not associated with pancreatic cancer when compared with control subjects with diabetes (HR 1.36, 95% CI 0.94–1.96); however, the ‘new user’ design did show an association between incretin use and pancreatic cancer when compared with control subjects with diabetes. In both cohorts with prevalent and incident users of antidiabetic drugs, the risk of pancreatic cancer almost doubled in those who had recently initiated incretin therapy (up to seven prescriptions), whereas this elevated risk dropped to baseline levels with prolonged use.
Conclusions
We found that incretin use was not associated with pancreatic cancer after adjustment for the severity of the underlying Type 2 Diabetes Mellitus (T2DM). The elevated risk of pancreatic cancer in those recently initiating incretin agents is likely to be caused by protopathic bias or other types of unknown distortion. The presence of considerable confounding by disease severity and the lack of a duration‐of‐use relationship do not support a causal explanation for the association between incretin agents and pancreatic cancer.
Summary
Higher incidences of fractures are seen in people with type 1 diabetes (T1D), but knowledge on different fracture sites is sparse. We found a higher incidence mainly for distal fracture sites ...in people with T1D compared to controls. It must be further studied which fractures attributed to the higher incidence rates (IRs) at specific sites.
Introduction
People with T1D have a higher incidence of fractures compared to the general population. However, sparse knowledge exists on the incidence rates of individual fracture sites. Therefore, we examined the incidence of various fracture sites in people with newly treated T1D compared to matched controls.
Methods
All people from the UK Clinical Practice Research Datalink GOLD (1987–2017), of all ages with a T1D diagnosis code (
n
= 6381), were included. People with T1D were matched by year of birth, sex, and practice to controls (
n
= 6381). Fracture IRs and incidence rate ratios (IRRs) were calculated. Analyses were stratified by fracture site and sex.
Results
The IR of all fractures was significantly higher in people with T1D compared to controls (IRR: 1.39 (CI95%: 1.24–1.55)). Compared to controls, the IRR for people with T1D was higher for several fracture sites including carpal (IRR: 1.41 (CI95%: 1.14–1.75)), clavicle (IRR: 2.10 (CI95%: 1.18–3.74)), foot (IRR: 1.70 (CI95%: 1.23–2.36)), humerus (IRR: 1.46 (CI95%: 1.04–2.05)), and tibia/fibula (IRR: 1.67 CI95%: 1.08–2.59)). In women with T1D, higher IRs were seen at the ankle (IRR: 2.25 (CI95%: 1.10–4.56)) and foot (IRR: 2.11 (CI95%: 1.27–3.50)), whereas in men with T1D, higher IRs were seen for carpal (IRR: 1.45 (CI95%: 1.14–1.86)), clavicle (IRR: 2.13 (CI95%: 1.13–4.02)), and humerus (IRR: 1.77 (CI95%: 1.10–2.83)) fractures.
Conclusion
The incidence of carpal, clavicle, foot, humerus, and tibia/fibula fractures was higher in newly treated T1D, but there was no difference at other fracture sites compared to controls. Therefore, the higher incidence of fractures in newly treated people with T1D has been found mainly for distal fracture sites.
Physical capacity (PC) and physical activity (PA) are associated physical performance measures, and combined, PC and PA are used to categorize physical performance in the “can do, do do” framework. ...We aimed to explore physical performance of patients attending the fracture liaison service (FLS). In this cross-sectional study, PC was measured by 6-min-walking-test (can’t do/can do) and PA by accelerometer (don’t do/do do). Following quadrants were defined based on predefined cut-off scores for poor performance: (1) “can’t do, don’t do”; (2) “can do, don’t do”; (3) “can’t do, do do”; (4) “can do, do do”. Odds ratios (OR) were calculated and fall and fracture risk factors were assessed between quadrants. Physical performance of 400 fracture patients was assessed (mean age 64; female 70.8%). Patients performed as follows: 8.3% “can’t do, don’t do”; 3.0% “can do, don’t do”; 19.3% “can’t do, do do”; 69.5% “can do, do do”. For the “can’t do” group the OR for low PA was 9.76 (95% CI: 4.82–19.80). Both the “can’t do, don’t do” and “can’t do, do do” group differed significantly compared to the “can do, do do” group on several fall and fracture risk factors and had lower physical performance. The “can do, do do” framework is able to identify fracture patients with an impaired physical performance. Of all FLS patients 20% “can’t do, but “do do” while having a high prevalence of fall risk factors compared to persons that “can do, do do”, which may indicate this group is prone to fall.
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