Life expectancy has increased over the last century in all high-income countries, including Engla... more Life expectancy has increased over the last century in all high-income countries, including England and Wales. Partly as a consequence of that, the age structure of the population of these countries has changed. A greater proportion of the population was elderly in 2007 than in 1971 and in 1971 than in 1901. Thomas McKeown famously analysed the decline in mortality rates in England and Wales from the mid-19th century to 1971, and put the major part of it down to a reduction in infectious diseases (McKeown, 1979). The decline in infections was largely the result, he suggested, of improvements in nutrition, improvements in the safety of water and better sanitation, as well as changes in personal behaviour. We have extended McKeown's analysis up to 2007 and have found that the story looks very different for the period 1971-2007. In the last four decades, approximately one fifth of the fall in age-standardised mortality rates in England and Wales is attributable to reductions in infectious diseases, and four fifths to non-infectious diseases. With regard to the individual disease groups, almost half of the fall in mortality rates between 1971 and 2007 was due to a fall in age-standardised mortality rates from cardiovascular disease. We also present evidence to suggest that a different picture may be observed when examining the extent of illness in the population, not just death rates. For example, although mortality rates from cardiovascular disease have declined in recent years, incidence rates have increased.
Introduction 2. Medicines expenditure and use in primary care in Wales 2.1. Comparative use of pr... more Introduction 2. Medicines expenditure and use in primary care in Wales 2.1. Comparative use of primary care medicines in Wales 2.2. Medicines expenditure per capita 2.3. Medicines as a proportion of NHS spending 2.4. Uptake of new medicines in the UK 2.5.The medicines bill in future 3. Health demographics 4. Quality and Outcomes Framework targets 5.Trends in NICE ands AWMSG health technology appraisals 6. Conclusions Appendix 1: Dispensing costs Appendix 2: Health demographics A1. Age distribution of the population A2. An increasing challenge to health in Wales A3. Limiting long-term illness A4. Chronic conditions Appendix 3: Uptake of new medicines positively appraised by NICE References and Sources Glossary 2 ABPI-Association of the British Pharmaceutical Industry AWMSG-All Wales Medicines Strategy Group CHD-Coronary Heart Disease COPD-Chronic Obstructive Pulmonary Disease Target Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the lower quartile or show an increase towards the quartile below Maintain performance levels within the upper quartile or show an increase towards the quartile above
... iv List of Tables and Figures Figure 1.21 Percentage who drank more than 3 or 4 units on at l... more ... iv List of Tables and Figures Figure 1.21 Percentage who drank more than 3 or 4 units on at least one day in the last week by sex ... 2005 71 Figure 1.22 Annual consumption of pure alcohol (in litres) per person aged 15 and over in selected OECD and EU countries, circa 2005 72 ...
In a seeming effort to advance the doublet of carfilzomib + dexamethasone as the preferred treatm... more In a seeming effort to advance the doublet of carfilzomib + dexamethasone as the preferred treatment option for relapsed/refractory multiple myeloma, Panjabi and Iskander of Amgen (Amgen, South San Francisco and Thousand Oaks, California) challenge our recent network meta-analysis (NMA) on the comparative efficacy of treatments for previously treated multiple myeloma. 1 Considering the paucity and lack of depth of their arguments in addition to the questionable scientific and clinical rationale, we challenge herein Panjabi and Iskander's position that our NMA "should not be used to inform treatment decisions because the analysis was significantly flawed" as well as their innuendo that a carfilzomib-based doublet offers better efficacy than other treatments based on naive, cross-trial comparisons of medians. Panjabi and Iskander suggest that the trials included in the NMA violated the similarity and consistency of assumptions in NMAs, leading to biased treatment effects. In support, they cite part 2 of the publication from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Indirect Treatment Comparisons Good Research Practices, Conducting Indirect Treatment Comparison/Network Meta-analysis Studies. 2 That report indeed addresses the issue of similarity but with a caution, citing Fu et al, 3 that "no commonly accepted standard [defines] which studies are 'similar enough.'" Panjabi and Iskander do not specify their criteria for similarity, nor do they offer evidence as to how our NMA violated the similarity assumption. Similarly, the ISPOR guideline emphasizes that consistency is a property of direct and indirect evidence for treatment comparisons, not of individual comparisons. However, Panjabi and Iskander seem to assume the latter in their rather singular focus on carfilzomib. As we noted within the Discussion section of the article, 1 we concur with the literature that NMAs have limitationsdand so does ours. However, just as much and despite these limitations, we concur with the field that there is a distinct need to support clinicians in appraising the comparative efficacy of treatment options based on the available evidence base. The synthesis of trial results through NMA is a well-recognized scientific, clinical, and regulatory approach to enabling broader comparative efficacy questions to be addressed when head-to-head evidence is lackingdand most likely never will exist. As part of the analysis, heterogeneity and consistency analyses were performed and did not show any significant differences or indicate bias. Due to the small size of the network, adjustment for baseline characteristics was inconclusive. We agree that it would be preferable if an NMA like ours could additionally consider the comparative efficacy of treatments using overall survival and quality of life. However, as Panjabi and Iskander noted, quality of life has been inconsistently reported in relapsed/refractory multiple myeloma treatment trials, but they fail to acknowledge that this inconsistency makes an NMA evaluating quality of life infeasible. Overall survival data from the CASTOR (Phase 3 Study Comparing Daratumumab, Bortezomib, and Dexamethasone [DVd] vs Bortezomib and Dexamethasone [Vd] in Subjects With Relapsed or Refractory Multiple Myeloma) 4 and POLLUX (Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone [DRd] vs Lenalidomide and Dexamethasone [Rd] in Subjects With Relapsed or Refractory Multiple Myeloma) 5 trials were immature at the time of the analysis, with median overall survival not yet reacheddwhich has been sufficiently convincing to scientists, clinicians, and regulators. Further, without patient-level data, differences in complex treatment pathways postprogression across trials cannot be fully addressed, preventing comparison analyses of overall survival across trials adjusted for differential postprogression treatments. In addition, while we agree that considering safety profiles between treatments is of interest, the feasibility of including safety is limited to only those adverse events that are the same across treatments. For example, if one treatment is associated with a particular adverse event that is not observed with another treatment, then the odds ratio estimated in the NMA would be infinite. The NMA would then not provide a clear comparison of adverseeevents profiles, when those profiles differ by treatment. Thus, we agree with Panjabi and Iskander that, in principle and in retrospect, data on quality of life, overall survival, and safety would have been of interest. We āŖāŖāŖ xxxx 1 Clinical Therapeutics/Volume xxx, Number xxx, xxxx
Objective To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sc... more Objective To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sclerosis (RMS) treated with ocrelizumab or ofatumumab and the relationship between Ig levels and infections. Methods A systematic literature review (SLR) was conducted to identify clinical trials and real-world evidence (RWE) studies on Ig levels over time and studies on associations with infections for ocrelizumab and ofatumumab for people with RMS through 10 September 2021. Searches were conducted in Embase, MEDLINE, Cochrane Library, trial registries, and recent conference abstracts. Results Of 1,580 articles identified, 30 reporting on 11 trials and 5 RWE studies were included. Ocrelizumab trials (nā=ā4) had 24ā336Ā weeks of follow-up and reported decreasing Ig G (IgG) levels, while RWE (nā=ā5) had 52ā78Ā weeks of follow-up and reported IgG to be stable or decrease only slightly. IgG levels were stable in ofatumumab trials (nā=ā5; 104ā168Ā weeks of follow-up), but no RWE or longer-term s...
Background: Daratumumab has recently been approved in the United States (US) for patients with mu... more Background: Daratumumab has recently been approved in the United States (US) for patients with multiple myeloma (MM). In the CASTOR clinical trial of patients who had received at least one prior line of therapy, daratumumab plus bortezomib and dexamethasone (DVd) showed significant improvements in clinical efficacy compared to bortezomib plus dexamethasone (Vd) (Palumbo, NEJM, 2016). However, limited information is available on the cost-effectiveness of DVd. A decision-analytic model was developed to consider direct medical costs from a US payer perspective and to explore the cost-effectiveness of DVd versus Vd in previously treated MM and in a subgroup of patients with only one prior line of therapy (first relapse). Methods: The model structure took the form of a partitioned survival analysis with three health states: progression-free survival (PFS), progressive disease, and death. A range of parametric survival functions were fitted to patient-level PFS data from the CASTOR trial ...
Background: The etiology of muscle wasting in chronic obstructive pulmonary disease (COPD) is inc... more Background: The etiology of muscle wasting in chronic obstructive pulmonary disease (COPD) is incompletely understood. We previously showed that the D rather than the I polymorphic variant of the angiotensin-converting enzyme (ACE) gene is associated with preserved quadriceps strength in COPD. If the ACE D allele influences skeletal muscle through increased ACE-related kinin degradation [and reduced activity at the bradykinin type 2 receptor (BK2R)], we might expect a similar association with the 9 BK2R genotype in this population as well. Objective: The objective was to test the hypothesis that the BK2R gene polymorphism is a determinant of fat-free mass and quadriceps strength in patients with COPD. Design: In a cross-sectional design we determined BK2R genotype, fat-free mass, and quadriceps strength in 110 COPD patients with a mean ( SD) predicted forced expiratory volume in 1 s of 34.3 16.4% and in 104 healthy age-matched control subjects. Results: The mean ( SD) fat-free mass ...
EBM is being added to the new curriculum, and will be examinable in future. It is a most importan... more EBM is being added to the new curriculum, and will be examinable in future. It is a most important topic, as it deals with critical appraisal of published papers, a skill that is not intuitive, but must be learned and studied. This lecture will be added to a bank of resources for registrar study on this topic, in addition to Skin Schools on the topic, and a new module to be added to the College website. This lecture will introduce some important concepts including the hierarchy of evidence, sensitivity, specificity, OR, RR, Likelihood ratios, PPV, NPV etc. P values and confidence intervals are concepts that many people talk about every day, but perhaps do not understand as deeply as they think. Different types of studies will be discussed and the biases inherent in them. Registrars' Forum Assessment of delays to diagnosis of nodular melanoma compared to superficial spreading melanoma
e20037Background: New treatments for relapsed/refractory multiple myeloma have recently been FDA ... more e20037Background: New treatments for relapsed/refractory multiple myeloma have recently been FDA approved in the United States (US). For FDA approval, these treatments are compared to historic stan...
ABSTRACT Heme-oxygenase 1 (HO-1) is a rate-limiting enzyme in the degradation of heme to bilirubi... more ABSTRACT Heme-oxygenase 1 (HO-1) is a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide (CO) and may have significant anti-inflammatory function. The HO-1 gene promoter region shows microsatellite polymorphism with different (GT)n repeats, reported to differently induce gene expression, with the short allele associated with higher gene expression. We measured the acute inflammatory response using coronary artery bypass surgery (CABG) as a well-characterized and uniform stimulus and examined the correlation between levels of IL-6, C-reactive protein (CRP) and fibrinogen and their relationship to HO-1 genotype. Two hundred and seventy-five consecutive patients undergoing CABG were genotyped for the HO-1 promoter polymorphism using PCR and automated DNA capillary sequencer. IL-6, CRP and fibrinogen were measured at baseline and 6, 24, 48, 72, 96 and 120 hours after CABG. Complete IL-6, CRP and fibrinogen measures were available in 220 patients. Before surgery IL-6 levels showed a strong correlation with CRP and fibrinogen (r = 0.48, P < 0.0001; r = 0.41, P < 0.0001 respectively), with a significant correlation between CRP and fibrinogen (r = 0.61, P < 0.0001). All three acute phase reactants showed a significant increase after CABG. After surgery, peak IL-6 was strongly correlated with peak CRP (r = 0.34, P = 0.0009) but not with peak fibrinogen (r = 0.15, P = 0.13), while peak CRP and peak fibrinogen were significantly correlated (r = 0.415, P < 0.0001). HO-1 allelic repeats ranged from 22-42, with (GT)25 and (GT)32 being the two most common alleles, and subsequently divided into three groups according to previous published work: <30 (GT)n were designated as S (short), 30-37 (GT)n as M (middle) and long repeats with >37 (GT)n as L (long); allele frequency 0.35, 0.58 and 0.07 respectively. Baseline CRP differed by genotype: those carrying at least one long allele having higher CRP than those with no long allele (3.76 +/- 0.79 vs. 2.07 +/- 0.17, P = 0.013). Conversely, those carrying at least one short allele had higher fibrinogen levels than those with no short allele (3.83 +/- 0.79 vs. 3.51 +/- 0.88, P = 0.006). There is a strong correlation between the measured acute phase reactants both at baseline and after the inflammatory response to CABG in patients with coronary disease. There was an association between the HO-1 microsatellite polymorphism and CRP and fibrinogen levels at baseline but there was no similar association following CABG. This may indicate that HO-1 is associated with chronic atherosclerotic inflammatory processes rather than acute.
Please note - an updated version of this publication is available [here]( https://www.ohe.org/pub... more Please note - an updated version of this publication is available [here]( https://www.ohe.org/publications/ohe-guide-uk-health-and-health-care-statistics). This publication provides both up-to-date statistics and a guide to finding and using health statistics from the UK and, to some extent, other OECD countries. Data are presented in easy to read tables and figures. The OHE Guide helps answer the following questions. - Where do I look for statistics? - What sorts of statistics do governmental and non-governmental bodies produce? - What do they cover? - How do I find them? - When I find them, how do I use them or where do I go for help and advice? The OHE Guide consists of four sections, plus a glossary and references. Demographics - demographic issues from the population census; population estimates and projections; mortality statistics and summary measures, including life expectancy and standardisation techniques; and the collection and use of morbidity and lifestyle statistics He...
Aim: Identify and describe published literature on the use of subcutaneous immunoglobulin (SCIG) ... more Aim: Identify and describe published literature on the use of subcutaneous immunoglobulin (SCIG) as initial immunoglobulin (IG)-replacement therapy for patients with primary immunodeficiency diseases (PID). Methods: We systematically identified and summarized literature in MEDLINE, Embase, BioSciences Information Service and Cochrane Library assessing efficacy/effectiveness, safety/tolerability, health-related quality-of-life (HRQoL) and dosing regimens of SCIG for IG-naive patients with PID. Results: Sixteen studies were included. In IG-naive patients, SCIG managed/reduced infections and demonstrated similar pharmacokinetic parameters to IG-experienced patients; adverse events were mostly minor injection-site pain or discomfort. Three studies reported improvements in HRQoL. Quality of studies was difficult to assess due to limited reporting. Conclusion: Although studies were lacking, available data suggest IG-naive and IG-experienced patients initiating SCIG likely have similar out...
Crack is one of the crucial causes of structural failure. A methodology for quantitative crack id... more Crack is one of the crucial causes of structural failure. A methodology for quantitative crack identification is proposed in this paper based on multivariable wavelet finite element method and particle swarm optimization. First, the structure with crack is modeled by multivariable wavelet finite element method (MWFEM) so that the vibration parameters of the first three natural frequencies in arbitrary crack conditions can be obtained, which is named as the forward problem. Second, the structure with crack is tested to obtain the vibration parameters of first three natural frequencies by modal testing and advanced vibration signal processing method. Then, the analyzed and measured first three natural frequencies are combined together to obtain the location and size of the crack by using particle swarm optimization. Compared with traditional wavelet finite element method, MWFEM method can achieve more accurate vibration analysis results because it interpolates all the solving variables at one time, which makes the MWFEM-based method to improve the accuracy in quantitative crack identification. In the end, the validity and superiority of the proposed method are verified by experiments of both cantilever beam and simply supported beam.
SummaryPlasma concentrations of coagulation factorVII (FVII) are determined by environmental and ... more SummaryPlasma concentrations of coagulation factorVII (FVII) are determined by environmental and genetic factors. The influence of functional polymorphisms in the FVII geneā¦
Life expectancy has increased over the last century in all high-income countries, including Engla... more Life expectancy has increased over the last century in all high-income countries, including England and Wales. Partly as a consequence of that, the age structure of the population of these countries has changed. A greater proportion of the population was elderly in 2007 than in 1971 and in 1971 than in 1901. Thomas McKeown famously analysed the decline in mortality rates in England and Wales from the mid-19th century to 1971, and put the major part of it down to a reduction in infectious diseases (McKeown, 1979). The decline in infections was largely the result, he suggested, of improvements in nutrition, improvements in the safety of water and better sanitation, as well as changes in personal behaviour. We have extended McKeown's analysis up to 2007 and have found that the story looks very different for the period 1971-2007. In the last four decades, approximately one fifth of the fall in age-standardised mortality rates in England and Wales is attributable to reductions in infectious diseases, and four fifths to non-infectious diseases. With regard to the individual disease groups, almost half of the fall in mortality rates between 1971 and 2007 was due to a fall in age-standardised mortality rates from cardiovascular disease. We also present evidence to suggest that a different picture may be observed when examining the extent of illness in the population, not just death rates. For example, although mortality rates from cardiovascular disease have declined in recent years, incidence rates have increased.
Introduction 2. Medicines expenditure and use in primary care in Wales 2.1. Comparative use of pr... more Introduction 2. Medicines expenditure and use in primary care in Wales 2.1. Comparative use of primary care medicines in Wales 2.2. Medicines expenditure per capita 2.3. Medicines as a proportion of NHS spending 2.4. Uptake of new medicines in the UK 2.5.The medicines bill in future 3. Health demographics 4. Quality and Outcomes Framework targets 5.Trends in NICE ands AWMSG health technology appraisals 6. Conclusions Appendix 1: Dispensing costs Appendix 2: Health demographics A1. Age distribution of the population A2. An increasing challenge to health in Wales A3. Limiting long-term illness A4. Chronic conditions Appendix 3: Uptake of new medicines positively appraised by NICE References and Sources Glossary 2 ABPI-Association of the British Pharmaceutical Industry AWMSG-All Wales Medicines Strategy Group CHD-Coronary Heart Disease COPD-Chronic Obstructive Pulmonary Disease Target Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the lower quartile or show a reduction towards the quartile below Maintain performance levels within the upper quartile or show an increase towards the quartile above Maintain performance levels within the lower quartile or show an increase towards the quartile below Maintain performance levels within the upper quartile or show an increase towards the quartile above
... iv List of Tables and Figures Figure 1.21 Percentage who drank more than 3 or 4 units on at l... more ... iv List of Tables and Figures Figure 1.21 Percentage who drank more than 3 or 4 units on at least one day in the last week by sex ... 2005 71 Figure 1.22 Annual consumption of pure alcohol (in litres) per person aged 15 and over in selected OECD and EU countries, circa 2005 72 ...
In a seeming effort to advance the doublet of carfilzomib + dexamethasone as the preferred treatm... more In a seeming effort to advance the doublet of carfilzomib + dexamethasone as the preferred treatment option for relapsed/refractory multiple myeloma, Panjabi and Iskander of Amgen (Amgen, South San Francisco and Thousand Oaks, California) challenge our recent network meta-analysis (NMA) on the comparative efficacy of treatments for previously treated multiple myeloma. 1 Considering the paucity and lack of depth of their arguments in addition to the questionable scientific and clinical rationale, we challenge herein Panjabi and Iskander's position that our NMA "should not be used to inform treatment decisions because the analysis was significantly flawed" as well as their innuendo that a carfilzomib-based doublet offers better efficacy than other treatments based on naive, cross-trial comparisons of medians. Panjabi and Iskander suggest that the trials included in the NMA violated the similarity and consistency of assumptions in NMAs, leading to biased treatment effects. In support, they cite part 2 of the publication from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Indirect Treatment Comparisons Good Research Practices, Conducting Indirect Treatment Comparison/Network Meta-analysis Studies. 2 That report indeed addresses the issue of similarity but with a caution, citing Fu et al, 3 that "no commonly accepted standard [defines] which studies are 'similar enough.'" Panjabi and Iskander do not specify their criteria for similarity, nor do they offer evidence as to how our NMA violated the similarity assumption. Similarly, the ISPOR guideline emphasizes that consistency is a property of direct and indirect evidence for treatment comparisons, not of individual comparisons. However, Panjabi and Iskander seem to assume the latter in their rather singular focus on carfilzomib. As we noted within the Discussion section of the article, 1 we concur with the literature that NMAs have limitationsdand so does ours. However, just as much and despite these limitations, we concur with the field that there is a distinct need to support clinicians in appraising the comparative efficacy of treatment options based on the available evidence base. The synthesis of trial results through NMA is a well-recognized scientific, clinical, and regulatory approach to enabling broader comparative efficacy questions to be addressed when head-to-head evidence is lackingdand most likely never will exist. As part of the analysis, heterogeneity and consistency analyses were performed and did not show any significant differences or indicate bias. Due to the small size of the network, adjustment for baseline characteristics was inconclusive. We agree that it would be preferable if an NMA like ours could additionally consider the comparative efficacy of treatments using overall survival and quality of life. However, as Panjabi and Iskander noted, quality of life has been inconsistently reported in relapsed/refractory multiple myeloma treatment trials, but they fail to acknowledge that this inconsistency makes an NMA evaluating quality of life infeasible. Overall survival data from the CASTOR (Phase 3 Study Comparing Daratumumab, Bortezomib, and Dexamethasone [DVd] vs Bortezomib and Dexamethasone [Vd] in Subjects With Relapsed or Refractory Multiple Myeloma) 4 and POLLUX (Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone [DRd] vs Lenalidomide and Dexamethasone [Rd] in Subjects With Relapsed or Refractory Multiple Myeloma) 5 trials were immature at the time of the analysis, with median overall survival not yet reacheddwhich has been sufficiently convincing to scientists, clinicians, and regulators. Further, without patient-level data, differences in complex treatment pathways postprogression across trials cannot be fully addressed, preventing comparison analyses of overall survival across trials adjusted for differential postprogression treatments. In addition, while we agree that considering safety profiles between treatments is of interest, the feasibility of including safety is limited to only those adverse events that are the same across treatments. For example, if one treatment is associated with a particular adverse event that is not observed with another treatment, then the odds ratio estimated in the NMA would be infinite. The NMA would then not provide a clear comparison of adverseeevents profiles, when those profiles differ by treatment. Thus, we agree with Panjabi and Iskander that, in principle and in retrospect, data on quality of life, overall survival, and safety would have been of interest. We āŖāŖāŖ xxxx 1 Clinical Therapeutics/Volume xxx, Number xxx, xxxx
Objective To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sc... more Objective To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sclerosis (RMS) treated with ocrelizumab or ofatumumab and the relationship between Ig levels and infections. Methods A systematic literature review (SLR) was conducted to identify clinical trials and real-world evidence (RWE) studies on Ig levels over time and studies on associations with infections for ocrelizumab and ofatumumab for people with RMS through 10 September 2021. Searches were conducted in Embase, MEDLINE, Cochrane Library, trial registries, and recent conference abstracts. Results Of 1,580 articles identified, 30 reporting on 11 trials and 5 RWE studies were included. Ocrelizumab trials (nā=ā4) had 24ā336Ā weeks of follow-up and reported decreasing Ig G (IgG) levels, while RWE (nā=ā5) had 52ā78Ā weeks of follow-up and reported IgG to be stable or decrease only slightly. IgG levels were stable in ofatumumab trials (nā=ā5; 104ā168Ā weeks of follow-up), but no RWE or longer-term s...
Background: Daratumumab has recently been approved in the United States (US) for patients with mu... more Background: Daratumumab has recently been approved in the United States (US) for patients with multiple myeloma (MM). In the CASTOR clinical trial of patients who had received at least one prior line of therapy, daratumumab plus bortezomib and dexamethasone (DVd) showed significant improvements in clinical efficacy compared to bortezomib plus dexamethasone (Vd) (Palumbo, NEJM, 2016). However, limited information is available on the cost-effectiveness of DVd. A decision-analytic model was developed to consider direct medical costs from a US payer perspective and to explore the cost-effectiveness of DVd versus Vd in previously treated MM and in a subgroup of patients with only one prior line of therapy (first relapse). Methods: The model structure took the form of a partitioned survival analysis with three health states: progression-free survival (PFS), progressive disease, and death. A range of parametric survival functions were fitted to patient-level PFS data from the CASTOR trial ...
Background: The etiology of muscle wasting in chronic obstructive pulmonary disease (COPD) is inc... more Background: The etiology of muscle wasting in chronic obstructive pulmonary disease (COPD) is incompletely understood. We previously showed that the D rather than the I polymorphic variant of the angiotensin-converting enzyme (ACE) gene is associated with preserved quadriceps strength in COPD. If the ACE D allele influences skeletal muscle through increased ACE-related kinin degradation [and reduced activity at the bradykinin type 2 receptor (BK2R)], we might expect a similar association with the 9 BK2R genotype in this population as well. Objective: The objective was to test the hypothesis that the BK2R gene polymorphism is a determinant of fat-free mass and quadriceps strength in patients with COPD. Design: In a cross-sectional design we determined BK2R genotype, fat-free mass, and quadriceps strength in 110 COPD patients with a mean ( SD) predicted forced expiratory volume in 1 s of 34.3 16.4% and in 104 healthy age-matched control subjects. Results: The mean ( SD) fat-free mass ...
EBM is being added to the new curriculum, and will be examinable in future. It is a most importan... more EBM is being added to the new curriculum, and will be examinable in future. It is a most important topic, as it deals with critical appraisal of published papers, a skill that is not intuitive, but must be learned and studied. This lecture will be added to a bank of resources for registrar study on this topic, in addition to Skin Schools on the topic, and a new module to be added to the College website. This lecture will introduce some important concepts including the hierarchy of evidence, sensitivity, specificity, OR, RR, Likelihood ratios, PPV, NPV etc. P values and confidence intervals are concepts that many people talk about every day, but perhaps do not understand as deeply as they think. Different types of studies will be discussed and the biases inherent in them. Registrars' Forum Assessment of delays to diagnosis of nodular melanoma compared to superficial spreading melanoma
e20037Background: New treatments for relapsed/refractory multiple myeloma have recently been FDA ... more e20037Background: New treatments for relapsed/refractory multiple myeloma have recently been FDA approved in the United States (US). For FDA approval, these treatments are compared to historic stan...
ABSTRACT Heme-oxygenase 1 (HO-1) is a rate-limiting enzyme in the degradation of heme to bilirubi... more ABSTRACT Heme-oxygenase 1 (HO-1) is a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide (CO) and may have significant anti-inflammatory function. The HO-1 gene promoter region shows microsatellite polymorphism with different (GT)n repeats, reported to differently induce gene expression, with the short allele associated with higher gene expression. We measured the acute inflammatory response using coronary artery bypass surgery (CABG) as a well-characterized and uniform stimulus and examined the correlation between levels of IL-6, C-reactive protein (CRP) and fibrinogen and their relationship to HO-1 genotype. Two hundred and seventy-five consecutive patients undergoing CABG were genotyped for the HO-1 promoter polymorphism using PCR and automated DNA capillary sequencer. IL-6, CRP and fibrinogen were measured at baseline and 6, 24, 48, 72, 96 and 120 hours after CABG. Complete IL-6, CRP and fibrinogen measures were available in 220 patients. Before surgery IL-6 levels showed a strong correlation with CRP and fibrinogen (r = 0.48, P < 0.0001; r = 0.41, P < 0.0001 respectively), with a significant correlation between CRP and fibrinogen (r = 0.61, P < 0.0001). All three acute phase reactants showed a significant increase after CABG. After surgery, peak IL-6 was strongly correlated with peak CRP (r = 0.34, P = 0.0009) but not with peak fibrinogen (r = 0.15, P = 0.13), while peak CRP and peak fibrinogen were significantly correlated (r = 0.415, P < 0.0001). HO-1 allelic repeats ranged from 22-42, with (GT)25 and (GT)32 being the two most common alleles, and subsequently divided into three groups according to previous published work: <30 (GT)n were designated as S (short), 30-37 (GT)n as M (middle) and long repeats with >37 (GT)n as L (long); allele frequency 0.35, 0.58 and 0.07 respectively. Baseline CRP differed by genotype: those carrying at least one long allele having higher CRP than those with no long allele (3.76 +/- 0.79 vs. 2.07 +/- 0.17, P = 0.013). Conversely, those carrying at least one short allele had higher fibrinogen levels than those with no short allele (3.83 +/- 0.79 vs. 3.51 +/- 0.88, P = 0.006). There is a strong correlation between the measured acute phase reactants both at baseline and after the inflammatory response to CABG in patients with coronary disease. There was an association between the HO-1 microsatellite polymorphism and CRP and fibrinogen levels at baseline but there was no similar association following CABG. This may indicate that HO-1 is associated with chronic atherosclerotic inflammatory processes rather than acute.
Please note - an updated version of this publication is available [here]( https://www.ohe.org/pub... more Please note - an updated version of this publication is available [here]( https://www.ohe.org/publications/ohe-guide-uk-health-and-health-care-statistics). This publication provides both up-to-date statistics and a guide to finding and using health statistics from the UK and, to some extent, other OECD countries. Data are presented in easy to read tables and figures. The OHE Guide helps answer the following questions. - Where do I look for statistics? - What sorts of statistics do governmental and non-governmental bodies produce? - What do they cover? - How do I find them? - When I find them, how do I use them or where do I go for help and advice? The OHE Guide consists of four sections, plus a glossary and references. Demographics - demographic issues from the population census; population estimates and projections; mortality statistics and summary measures, including life expectancy and standardisation techniques; and the collection and use of morbidity and lifestyle statistics He...
Aim: Identify and describe published literature on the use of subcutaneous immunoglobulin (SCIG) ... more Aim: Identify and describe published literature on the use of subcutaneous immunoglobulin (SCIG) as initial immunoglobulin (IG)-replacement therapy for patients with primary immunodeficiency diseases (PID). Methods: We systematically identified and summarized literature in MEDLINE, Embase, BioSciences Information Service and Cochrane Library assessing efficacy/effectiveness, safety/tolerability, health-related quality-of-life (HRQoL) and dosing regimens of SCIG for IG-naive patients with PID. Results: Sixteen studies were included. In IG-naive patients, SCIG managed/reduced infections and demonstrated similar pharmacokinetic parameters to IG-experienced patients; adverse events were mostly minor injection-site pain or discomfort. Three studies reported improvements in HRQoL. Quality of studies was difficult to assess due to limited reporting. Conclusion: Although studies were lacking, available data suggest IG-naive and IG-experienced patients initiating SCIG likely have similar out...
Crack is one of the crucial causes of structural failure. A methodology for quantitative crack id... more Crack is one of the crucial causes of structural failure. A methodology for quantitative crack identification is proposed in this paper based on multivariable wavelet finite element method and particle swarm optimization. First, the structure with crack is modeled by multivariable wavelet finite element method (MWFEM) so that the vibration parameters of the first three natural frequencies in arbitrary crack conditions can be obtained, which is named as the forward problem. Second, the structure with crack is tested to obtain the vibration parameters of first three natural frequencies by modal testing and advanced vibration signal processing method. Then, the analyzed and measured first three natural frequencies are combined together to obtain the location and size of the crack by using particle swarm optimization. Compared with traditional wavelet finite element method, MWFEM method can achieve more accurate vibration analysis results because it interpolates all the solving variables at one time, which makes the MWFEM-based method to improve the accuracy in quantitative crack identification. In the end, the validity and superiority of the proposed method are verified by experiments of both cantilever beam and simply supported beam.
SummaryPlasma concentrations of coagulation factorVII (FVII) are determined by environmental and ... more SummaryPlasma concentrations of coagulation factorVII (FVII) are determined by environmental and genetic factors. The influence of functional polymorphisms in the FVII geneā¦
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