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  • 1
    In: Gut, BMJ, Vol. 72, No. 3 ( 2023-03), p. 512-521
    Abstract: Prior studies identified clinical factors associated with increased risk of pancreatic ductal adenocarcinoma (PDAC). However, little is known regarding their time-varying nature, which could inform earlier diagnosis. This study assessed temporality of body mass index (BMI), blood-based markers, comorbidities and medication use with PDAC risk . Design We performed a population-based nested case–control study of 28 137 PDAC cases and 261 219 matched-controls in England. We described the associations of biomarkers with risk of PDAC using fractional polynomials and 5-year time trends using joinpoint regression. Associations with comorbidities and medication use were evaluated using conditional logistic regression. Results Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while following a U-shaped relationship for BMI and haemoglobin. Five-year trends showed biphasic BMI decrease and HbA1c increase prior to PDAC; early-gradual changes 2–3 years prior, followed by late-rapid changes 1–2 years prior. Liver markers and blood counts (white blood cell, platelets) showed monophasic rapid-increase approximately 1 year prior. Recent diagnosis of pancreatic cyst, pancreatitis, type 2 diabetes and initiation of certain glucose-lowering and acid-regulating therapies were associated with highest risk of PDAC. Conclusion Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while followed a U-shaped relationship for BMI and haemoglobin. BMI and HbA1c derange biphasically approximately 3 years prior while liver markers and blood counts (white blood cell, platelets) derange monophasically approximately 1 year prior to PDAC. Profiling these in combination with their temporality could inform earlier PDAC diagnosis.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2023
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  • 2
    In: Arthritis Care & Research, Wiley, Vol. 72, No. 1 ( 2020-01), p. 88-97
    Abstract: To develop and internally validate risk models and a clinical risk score tool to predict incident radiographic knee osteoarthritis ( RKOA ) in middle‐aged women. Methods We analyzed 649 women in the Chingford 1,000 Women study. The outcome was incident RKOA , defined as Kellgren/Lawrence grade 0–1 at baseline and ≥2 at year 5. We estimated predictors’ effects on the outcome using logistic regression models. Two models were generated. The clinical model considered patient characteristics, medication, biomarkers, and knee symptoms. The radiographic model considered the same factors, plus radiographic factors (e.g., angle between the acetabular roof and the ilium's vertical cortex [hip α‐angle]). The models were internally validated. Model performance was assessed using calibration and discrimination (area under the receiver characteristic curve [ AUC ]). Results The clinical model contained age, quadriceps circumference, and a cartilage degradation marker (C‐terminal telopeptide of type II collagen) as predictors ( AUC = 0.692). The radiographic model contained older age, greater quadriceps circumference, knee pain, knee baseline Kellgren/Lawrence grade 1 (versus 0), greater hip α‐angle, greater spinal bone mineral density, and contralateral RKOA at baseline as predictors ( AUC = 0.797). Calibration tests showed good agreement between the observed and predicted incident RKOA . A clinical risk score tool was developed from the clinical model. Conclusion Two models predicting incident RKOA within 4 years were developed, including radiographic variables that improved model performance. First‐time predictor hip α‐angle and contralateral RKOA suggest OA origins beyond the knee. The clinical tool has the potential to help physicians identify patients at risk of RKOA in routine practice, but the tool should be externally validated.
    Type of Medium: Online Resource
    ISSN: 2151-464X , 2151-4658
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 3
    In: Journal of Medical Virology, Wiley, Vol. 79, No. 11 ( 2007-11), p. 1617-1628
    Abstract: Human immunodeficiency virus type 1 (HIV‐1) antiviral drug resistance is a major consequence of therapy failure and compromises future therapeutic options. Nelfinavir and lopinavir/ritonavir‐based therapies have been widely used in the treatment of HIV‐infected patients, in combination with reverse transcriptase inhibitors. The aim of this observational study was the identification and characterization of mutations or combinations of mutations associated with resistance to nelfinavir and lopinavir/ritonavir in treated patients. Nucleotide sequences of 1,515 subtype B HIV‐1 isolates from 1,313 persons with different treatment histories (including naïve and treated patients) were collected in 31 Spanish hospitals over the years 2002–2005. Chi‐square contingency tests were performed to detect mutations associated with failure to protease inhibitor‐based therapies, and correlated mutations were identified using statistical methods. Virological failure to nelfinavir was associated with two different mutational pathways. D30N and N88D appeared mostly in patients without previous exposure to protease inhibitors, while K20T was identified as a secondary resistance mutation in those patients. On the other hand, L90M together with L10I, I54V, A71V, G73S, and V82A were selected in protease inhibitor‐experienced patients. A series of correlated mutations including L10I, M46I, I54V, A71V, G73S, and L90M appeared as a common cluster of amino acid substitutions, associated with failure to lopinavir/ritonavir‐based treatments. Despite the relatively high genetic barrier of some protease inhibitors, a relatively small cluster of mutations, previously selected under drug pressure, can seriously compromise the efficiency of nelfinavir‐ and lopinavir/ritonavir‐based therapies. J. Med. Virol. 79:1617–1628, 2007. © 2007 Wiley‐Liss, Inc.
    Type of Medium: Online Resource
    ISSN: 0146-6615 , 1096-9071
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2007
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  • 4
    Online Resource
    Online Resource
    Royal College of General Practitioners ; 2022
    In:  British Journal of General Practice Vol. 72, No. 717 ( 2022-04), p. e269-e275
    In: British Journal of General Practice, Royal College of General Practitioners, Vol. 72, No. 717 ( 2022-04), p. e269-e275
    Abstract: Guidelines recommend that GPs give patients lifestyle advice to manage hypertension and diabetes. Increasing evidence shows that this is an effective and practical treatment for these conditions, but it is unclear whether GPs offer this support. Aim To investigate trends in the percentage of patients with hypertension/diabetes receiving lifestyle advice versus medication. Design and setting This was a trend analysis of self-reported data from the annual Health Survey for England (HSE) (2003–2017) and GP-recorded data from the QResearch database (2002–2016). Method The percentage of patients with hypertension or diabetes who received lifestyle advice or medication was calculated in each year. Associations between likelihood of receiving lifestyle advice and characteristics were assessed using multivariable logistic regression. Results The percentage of patients receiving lifestyle advice was consistently lower than those receiving medication in both self-reported and medical records. There was consistent evidence of increasing trends in the percentage of patients with hypertension receiving lifestyle advice (HSE 13.8% to 20.1%; P trend 〈 0.001; QResearch 11.0% to 22.7%; P trend 〈 0.001). For diabetes, there was a non-significant decline in self-reported receipt of lifestyle advice (45.0% to 27.9%; P trend = 0.111) and a significant increase in medically recorded delivery of this advice (20.7% to 40.5%; P trend 〈 0.001). Patients with hypertension who were overweight or obese were more likely to receive lifestyle advice than those of a healthy weight, whereas the opposite was true for diabetes. Conclusion Only a minority of patients with diabetes or hypertension report receiving lifestyle advice or have this recorded in their medical records. Interventions beyond guidelines are needed to increase the delivery of behavioural interventions to treat these conditions.
    Type of Medium: Online Resource
    ISSN: 0960-1643 , 1478-5242
    RVK:
    Language: English
    Publisher: Royal College of General Practitioners
    Publication Date: 2022
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  • 5
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 54, No. 11 ( 2010-11), p. 4799-4811
    Abstract: Previous studies showed an increased prevalence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) thumb subdomain polymorphisms Pro272, Arg277, and Thr286 in patients failing therapy with nucleoside analogue combinations. Interestingly, wild-type HIV-1 BH10 RT contains Pro272, Arg277, and Thr286. Here, we demonstrate that in the presence of zidovudine, HIV-1 BH10 RT mutations P272A/R277K/T286A produce a significant reduction of the viral replication capacity in peripheral blood mononuclear cells in both the absence and presence of M41L/T215Y. In studies carried out with recombinant enzymes, we show that RT thumb subdomain mutations decrease primer-unblocking activity on RNA/DNA complexes, but not on DNA/DNA template-primers. These effects were observed with primers terminated with thymidine analogues (i.e., zidovudine and stavudine) and carbovir (the relevant derivative of abacavir) and were more pronounced when mutations were introduced in the wild-type HIV-1 BH10 RT sequence context. RT thumb subdomain mutations increased by 2-fold the apparent dissociation equilibrium constant ( K d ) for RNA/DNA without affecting the K d for DNA/DNA substrates. RNase H assays carried out with RNA/DNA complexes did not reveal an increase in the reaction rate or in secondary cleavage events that could account for the decreased excision activity. The interaction of Arg277 with the phosphate backbone of the RNA template in HIV-1 RT bound to RNA/DNA and the location of Thr286 close to the RNA strand are consistent with thumb polymorphisms playing a role in decreasing nucleoside RT inhibitor excision activity on RNA/DNA template-primers by affecting interactions with the template-primer duplex without involvement of the RNase H activity of the enzyme.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2010
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    SSG: 12
    SSG: 15,3
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  • 6
    Online Resource
    Online Resource
    Royal College of General Practitioners ; 2021
    In:  British Journal of General Practice Vol. 71, No. 710 ( 2021-09), p. e701-e710
    In: British Journal of General Practice, Royal College of General Practitioners, Vol. 71, No. 710 ( 2021-09), p. e701-e710
    Abstract: The NHS Health Check cardiovascular prevention programme is now 10 years old. Aim To describe NHS Heath Check attendance, new diagnoses, and treatment in relation to equity indicators. Design and setting A nationally representative database derived from 1500 general practices from 2009–2017. Method The authors compared NHS Health Check attendance and new diagnoses and treatments by age, sex, ethnic group, and deprivation. Results In 2013–2017, 590 218 (16.9%) eligible people aged 40–74 years attended an NHS Health Check and 2 902 598 (83.1%) did not attend. South Asian ethnic groups were most likely to attend compared to others, and females more than males. New diagnoses were more likely in attendees than non-attendees: hypertension 25/1000 in attendees versus 9/1000 in non-attendees; type 2 diabetes 8/1000 versus 3/1000; and chronic kidney disease (CKD) 7/1000 versus 4/1000. In people aged ≥65 years, atrial fibrillation was newly diagnosed in 5/1000 attendees and 3/1000 non-attendees, and for dementia 2/1000 versus 1/1000, respectively. Type 2 diabetes, hypertension, and CKD were more likely in more deprived groups, and in South Asian, Black African, and Black Caribbean ethnic groups. Attendees were more likely to be prescribed statins (26/1000) than non-attendees (8/1000), and antihypertensive medicines (25/1000 versus 13/1000 non-attendees). However, of the 117 963 people with ≥10% CVD risk who were eligible for statins, only 9785 (8.3%) were prescribed them. Conclusion Uptake of NHS Health Checks remains low. Attendees were more likely than non-attendees to be diagnosed with type 2 diabetes, hypertension, and CKD, and to receive treatment with statins and antihypertensives. Most attendees received neither treatment nor referral. Of those eligible for statins, 〈 10% were treated. Policy reviews should consider a targeted approach prioritising those at highest CVD risk for face-to-face contact and consider other options for those at lower CVD risk.
    Type of Medium: Online Resource
    ISSN: 0960-1643 , 1478-5242
    RVK:
    Language: English
    Publisher: Royal College of General Practitioners
    Publication Date: 2021
    detail.hit.zdb_id: 1043148-2
    detail.hit.zdb_id: 2097982-4
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  • 7
    In: Arthritis Care & Research, Wiley, Vol. 74, No. 3 ( 2022-03), p. 392-402
    Abstract: To estimate the costs of primary hip and knee replacement in individuals with osteoarthritis up to 2 years postsurgery, compare costs before and after the surgery, and identify predictors of hospital costs. Methods Patients age ≥18 years with primary planned hip or knee replacements and osteoarthritis in England between 2008 and 2016 were identified from the National Joint Registry and linked with Hospital Episode Statistics data containing inpatient episodes. Primary care data linked with hospital outpatient records were also used to identify patients age ≥18 years with primary hip or knee replacements between 2008 and 2016. All health care resource use was valued using 2016/2017 costs, and nonparametric censoring methods were used to estimate total 1‐year and 2‐year costs. Results We identified 854,866 individuals undergoing hip or knee replacement. The mean censor‐adjusted 1‐year hospitalization costs for hip and knee replacement were £7,827 (95% confidence interval [95% CI] 7,813, 7,842) and £7,805 (95% CI 7,790, 7,818), respectively. Complications and revisions were associated with up to a 3‐fold increase in 1‐year hospitalization costs. The censor‐adjusted 2‐year costs were £9,258 (95% CI 9,233, 9,280) and £9,452 (95% CI 9,430, 9,475) for hip and knee replacement, respectively. Adding primary and outpatient care, the mean total hip and knee replacement 2‐year costs were £11,987 and £12,578, respectively. Conclusion There are significant costs following joint replacement. Revisions and complications accounted for considerable costs and there is a significant incentive to identify best approaches to reduce these.
    Type of Medium: Online Resource
    ISSN: 2151-464X , 2151-4658
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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    detail.hit.zdb_id: 645059-3
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