5607 S Pulaski Rd
Chicago IL 60629
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Long-term conditions and medically-unexplained symptoms: feasibility of cognitive behavioural interventions within the improving access to Psychological Therapies Programme. - Journal of mental health (Abingdon, England)
Improving access to psychological therapies (IAPT) is a major programme in England to treat common mental health problems, mainly through cognitive behaviour therapy. In 2012, a Pathfinder scheme was launched to develop interventions for people with chronic physical health conditions or medically-unexplained symptoms.This qualitative component of the evaluation investigated feasibility and acceptability of IAPT provision for people with enduring physical health problems.Qualitative interviews were conducted with project leaders in all 14 Pathfinder sites.Various therapeutic and training interventions were introduced. Most patients received low-intensity, structured therapy, with high-intensity input provided by some Pathfinders for complex cases. Whether the focus was on psychological symptoms or on broader well-being, psychiatric terminology was avoided to improve utilisation. Participants perceived high satisfaction among service-users. Training needs were indicated for IAPT workers in this specialised work.Cognitive behaviour interventions appeared to be acceptable for people struggling with physical health problems. Robust outcome evidence will be pursued in Phase II.
Improving Osteoporosis Management in Primary Care: An Audit of the Impact of a Community Based Fracture Liaison Nurse. - PloS one
Osteoporosis and associated fragility fractures are a major health problem; they are more common in women over 50 years old. Fracture liaison nurses have been widely used in secondary care to promote the recognition of fragility fractures and to promote the use of bone-sparing medication to reduce the risk of recurrent facture.Audit the impact of a primary care based fracture liaison nurse on the detection of fragility fractures in people with osteoporosis and their treatment with a bone-sparing medication.This audit took place in 12 GP practices using 'before and after' cross-sectional extractions of anonymised routine data. We report, for females 50-74 years and â‰¥75 years old, socio-economic deprivation index, the prevalence of osteoporosis, recording of fragility fractures, dual-energy X-ray absorptiometry (DXA), smoking, and body-mass index (BMI) and use of appropriate bone-sparing medication. We used Altman's test of independent proportions to compare before and after data.Recording of the diagnosis of osteoporosis increased from 1.5% to 1.7% (p = 0.059); the rate of DXA scans fell (1.8% to 1.4%; p = 0.002); recording of fractures and fragility fractures more than doubled (0.8% to 2.0%; p<0.001 and 0.5% to 1.5%; p<0.001, respectively) with approximate doubling of the recording of smoking, and BMI (p<0.001 level). Fragility fracture recording rose from 8.8% to 15% in females aged 50 to 74, and from 0.8% to 2.3% in people aged â‰¥75years old (p<0.001). There appeared to be inequity in the service, people who were least deprived were more likely to receive DXA scans and the more deprived to be prescribed bone sparing agents.A fracture liaison nurse in primary care has been associated with a period of improved management. Liaison nurses based in different parts of the health system should be tested in a prospective trial.
Interactions of the hepatitis C virus protease inhibitor faldaprevir with cytochrome P450 enzymes: in vitro and in vivo correlation. - Journal of clinical pharmacology
The potential inhibition of the major human cytochrome P450 (CYP) enzymes by faldaprevir was evaluated both in vitro and in clinical studies (healthy volunteers and hepatitis C virus [HCV] genotype 1-infected patients). In vitro studies indicated that faldaprevir inhibited CYP2B6, CYP2C9, and CYP3A, and was a weak-to-moderate inactivator of CYP3A4. Faldaprevir 240â€‰mg twice daily in healthy volunteers demonstrated moderate inhibition of hepatic and intestinal CYP3A (oral midazolam: 2.96-fold increase in AUC(0-24â€‰h)), weak inhibition of hepatic CYP3A (intravenous midazolam: 1.56-fold increase in AUC(0-24â€‰h)), weak inhibition of CYP2C9 ([S]-warfarin: 1.29-fold increase in AUC(0-120â€‰h)), and had no relevant effects on CYP1A2, CYP2B6, or CYP2D6. Faldaprevir 120â€‰mg once daily in HCV-infected patients demonstrated weak inhibition of hepatic and intestinal CYP3A (oral midazolam: 1.52-fold increase in AUC(0-âˆž)), and had no relevant effects on CYP2C9 or CYP1A2. In vitro drug-drug interaction predictions based on inhibitor concentration ([I])/inhibition constant (Ki) ratios tended to overestimate clinical effects and a net-effect model provided a more accurate approach. These studies suggest that faldaprevir shows a dose-dependent inhibition of CYP3A and CYP2C9, and does not induce CYP isoforms.Â© 2015, The American College of Clinical Pharmacology.
Altered CYP2C9 activity following modulation of CYP3A4 levels in human hepatocytes: an example of protein-protein interactions. - Drug metabolism and disposition: the biological fate of chemicals
Cytochrome P450 (P450) protein-protein interactions resulting in modulation of enzyme activities have been well documented using recombinant isoforms. This interaction has been less clearly demonstrated in a more physiologic in vitro system such as human hepatocytes. As an expansion of earlier work (Subramanian et al., 2010), in which recombinant CYP2C9 activity decreased with increasing levels of CYP3A4, the current study modulated CYP3A4 content in human hepatocytes to determine the impact on CYP2C9. Modulation of CYP3A4 levels in situ was enabled by the use of a long-term human hepatocyte culture model (HepatoPac) shown to retain phenotypic hepatocyte function over a number of weeks. The extended period of culture allowed time for knockdown of CYP3A4 protein by small interfering RNA (siRNA) with subsequent recovery, as well as upregulation through induction with a recovery period. CYP3A4 gene silencing resulted in a 60% decrease in CYP3A4 activity and protein levels with a concomitant 74% increase in CYP2C9 activity, with no change in CYP2C9 mRNA levels. Upon removal of siRNA, both CYP2C9 and CYP3A4 activities returned to pre-knockdown levels. Importantly, modulation of CYP3A4 protein levels had no impact on cytochrome P450 reductase activities or levels. However, the possibility for competition for limiting reductase cannot be ruled out. Interestingly, lowering CYP3A4 levels also increased UDP-glucuronosyltransferase 2B7 activity. These studies clearly demonstrate that alterations in CYP3A4 levels can modulate CYP2C9 activity in situ and suggest that further studies are warranted to evaluate the possible clinical consequences of these findings.Copyright Â© 2014 by The American Society for Pharmacology and Experimental Therapeutics.
Development of a questionnaire to evaluate practitioners' confidence and knowledge in primary care in managing chronic kidney disease. - BMC nephrology
In the UK, chronic disease, including chronic kidney disease (CKD) is largely managed in primary care. We developed a tool to assess practitioner confidence and knowledge in managing CKD compared to other chronic diseases. This questionnaire was part of a cluster randomised quality improvement interventions in chronic kidney disease (QICKD; ISRCTN56023731).The questionnaire was developed by family physicians, primary care nurses, academics and renal specialists. We conducted three focus groups (n=7, 6, and 8) to refine the questionnaire using groups of general practitioners, practice nurses and trainees in general practice. We used paper based versions to develop the questionnaire and online surveys to test it. Practitioners in a group of volunteer, trial practices received the questionnaire twice. We measured its reliability using Cohen's Kappa (K).The practitioners in the focus groups reached a consensus as to the key elements to include in the instrument. We achieved a 73.1% (n=57/78) initial response rate for our questionnaire; of these 57, 54 completed the questionnaire a second time. Family physicians made up the largest single group of respondents (47.4%, n=27). Initial response showed more female (64.9%, n=37) than male (35.1%, n=20) respondents. The reliability results from retesting showed that there was moderate agreement (k>0.4) on all questions; with many showing substantial agreement (k>0.6). There was substantial agreement in the questions about loop diuretics (k=0.608, CI 0.432-0.784, p<0.001), confidence in managing hypertension (k=0.628, 95%CI 0.452-0.804, p<0.001), diastolic blood pressure treatment thresholds in CKD (k=0.608, 95%CI 0.436-0.780, p<0.001) and the rate of decline of eGFR that would prompt referral (k=0.764, 95%CI 0.603-0.925, p<0.001).The QICKD-CCQ is a reliable instrument for measuring confidence and knowledge among primary care practitioners on CKD management in the context of UK primary care.
Bridging in vitro and in vivo metabolism and transport of faldaprevir in human using a novel cocultured human hepatocyte system, HepatoPac. - Drug metabolism and disposition: the biological fate of chemicals
An increased appreciation of the importance of transporter and enzyme interplay in drug clearance and a desire to delineate these mechanisms necessitates the utilization of models that contain a full complement of enzymes and transporters at physiologically relevant activities. Additionally, the development of drugs with longer half-lives requires in vitro systems with extended incubation times that allow characterization of metabolic pathways for low-clearance drugs. A recently developed coculture hepatocyte model, HepatoPac, has been applied to meet these challenges. Faldaprevir is a drug in late-stage development for the treatment of hepatitis C. Faldaprevir is a low-clearance drug with the somewhat unique characteristic of being slowly metabolized, producing two abundant hydroxylated metabolites (M2a and M2b) in feces (âˆ¼40% of the dose) without exhibiting significant levels of circulating metabolites in humans. The human HepatoPac model was investigated to characterize the metabolism and transport of faldaprevir. In human HepatoPac cultures, M2a and M2b were the predominant metabolites formed, with extents of formation comparable to in vivo. Direct glucuronidation of faldaprevir was shown to be a minor metabolic pathway. HepatoPac studies also demonstrated that faldaprevir is concentrated in liver with active uptake by multiple transporters (including OATP1B1 and Na(+)-dependent transporters). Overall, human HepatoPac cultures provided valuable insights into the metabolism and disposition of faldaprevir in humans and demonstrated the importance of enzyme and transporter interplay in the clearance of the drug.
Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac. - Drug metabolism and disposition: the biological fate of chemicals
Generating accurate in vitro intrinsic clearance data is an important aspect of predicting in vivo human clearance. Primary hepatocytes in suspension are routinely used to predict in vivo clearance; however, incubation times have typically been limited to 4-6 hours, which is not long enough to accurately evaluate the metabolic stability of slowly metabolized compounds. HepatoPac is a micropatterened hepatocyte-fibroblast coculture system that can be used for continuous incubations of up to 7 days. This study evaluated the ability of human HepatoPac to predict the in vivo clearance (CL) of 17 commercially available compounds with low to intermediate clearance (<12 ml/min per kg). In vitro half-life for disappearance of each compound was converted to hepatic clearance using the well stirred model, with and without correction for plasma protein binding. Hepatic CL, using three individual donors, was accurately predicted for 10 of 17 compounds (59%; predicted clearance within 2-fold of observed human in vivo clearance values). The accuracy of prediction increased to 76% (13 of 17 compounds) with an acceptance criterion defined as within 3-fold. When considering only low clearance compounds (<5 ml/min per kg), which represented 10 of the 17 compounds, the accuracy of prediction was 60% within 2-fold and 90% within 3-fold. In addition, the turnover of three slowly metabolized compounds (alprazolam, meloxicam, and tolbutamide) in HepatoPac was directly compared with turnover in suspended hepatocytes. The turnover of alprazolam and tolbutamide was approximately 2-fold greater using HepatoPac compared with suspended hepatocytes, which was roughly in line with the extrapolated values (correcting for the longer incubation time and lower cell number with HepatoPac). HepatoPac, but not suspended hepatocytes, demonstrated significant turnover of meloxicam. These results demonstrate the utility of HepatoPac for prediction of in vivo hepatic clearance, particularly with low clearance compounds.
Improving the management of people with a family history of breast cancer in primary care: before and after study of audit-based education. - BMC family practice
In England, guidance from National Institute for Clinical Excellence (NICE) states women with a family history of breast cancer presenting to primary care should be reassured or referred.We reviewed the evidence for interventions that might be applied in primary care and conducted an audit of whether low risk women are correctly advised and flagged.We conducted a literature review to identify modifiable risk factors. We extracted routinely collected data from the computerised medical record systems of 6 general practices (population approximately 30,000); of the variables identified in the guidance. We implemented a quality improvement (QI) intervention called audit-based education (ABE) comparing participant practices with guidelines and each other before and after; we report odds ratios (OR) of any change in data recording.The review revealed evidence for advising on: diet, weight control, physical exercise, and alcohol. The proportion of patients with recordings of family history of: disease, neoplasms, and breast cancer were: 39.3%, 5.1% and 1.3% respectively. There was no significant change in the recording of family history of disease or cancer; OR 1.02 (95% CI 0.98-1.06); and 1.08 (95% CI 0.99-1.17) respectively. Recording of alcohol consumption and smoking both increased significantly; OR 1.36 (95% CI 1.30-1.43); and 1.42 (95% CI 1.27-1.60) respectively. Recording lifestyle advice fell; OR 0.84 (95% CI 0.81-0.88).The study informs about current data recording and willingness to engage in ABE. Recording of risk factors improved after the intervention. Further QI is needed to achieve adherence to current guidance.
Referral for psychological therapy of people with long term conditions improves adherence to antidepressants and reduces emergency department attendance: controlled before and after study. - Behaviour research and therapy
Referral to psychological therapies is recommended for people with common mental health problems (CMHP) however its impact on healthcare utilisation in people with long term conditions (LTCs) is not known.Routinely collected primary care, psychological therapy clinic and hospital data were extracted for the registered population of 20 practices (N = 121,199). These data were linked using the SAPREL (Secure and Private Record Linkage) method. We linked the 1118 people referred to psychological therapies with 6711 controls, matched for age, gender and practice. We compared utilisation of healthcare resources by people with LTCs, 6 months before and after referral, and conducted a controlled before and after study to compare health utilisation with controls. We made the assumption that collection of a greater number of repeat prescriptions for antidepressants was associated with greater adherence.Overall 21.8% of people with an LTC had CMHP vs. 18.8% without (p < 0.001). People with LTCs before referral were more likely to use health care resources (2-tailed t-test p < 0.001). Cases with LTCs showed referral to the psychological therapies clinic was associated with increased antidepressant medication prescribing (mean differences 0.62, p < 0.001) and less use of emergency department than controls (mean difference -0.21, p = 0.003).Referral to improved access to psychological therapies (IAPT) services appears of value to people with LTC. It is associated with the issue of a greater number of prescriptions for anti-depressant medicines and less use of emergency services. Further studies are needed to explore bed occupancy and outpatient attendance.Copyright Â© 2013 Elsevier Ltd. All rights reserved.
Audit-based education lowers systolic blood pressure in chronic kidney disease: the Quality Improvement in CKD (QICKD) trial results. - Kidney international
Strict control of systolic blood pressure is known to slow progression of chronic kidney disease (CKD). Here we compared audit-based education (ABE) to guidelines and prompts or usual practice in lowering systolic blood pressure in people with CKD. This 2-year cluster randomized trial included 93 volunteer general practices randomized into three arms with 30 ABE practices, 32 with guidelines and prompts, and 31 usual practices. An intervention effect on the primary outcome, systolic blood pressure, was calculated using a multilevel model to predict changes after the intervention. The prevalence of CKD was 7.29% (41,183 of 565,016 patients) with all cardiovascular comorbidities more common in those with CKD. Our models showed that the systolic blood pressure was significantly lowered by 2.41â€‰mmâ€‰Hg (CI 0.59-4.29â€‰mmâ€‰Hg), in the ABE practices with an odds ratio of achieving at least a 5â€‰mmâ€‰Hg reduction in systolic blood pressure of 1.24 (CI 1.05-1.45). Practices exposed to guidelines and prompts produced no significant change compared to usual practice. Male gender, ABE, ischemic heart disease, and congestive heart failure were independently associated with a greater lowering of systolic blood pressure but the converse applied to hypertension and age over 75 years. There were no reports of harm. Thus, individuals receiving ABE are more likely to achieve a lower blood pressure than those receiving only usual practice. The findings should be interpreted with caution due to the wide confidence intervals.
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5607 S Pulaski Rd Chicago, IL 60629
6441 S Pulaski Rd Suite 100
6625 S Pulaski Rd