We assessed the association of cerebrovascular disease with patient-reported outcomes (PROs) of moderate-severe activity limitation and moderate-severe pain at 2- and 5-years after primary total knee arthroplasty (TKA) using multivariable-adjusted logistic regression. 7,139 primary and 4,234 revision TKAs were included. Compared to the patients without cerebrovascular disease, those with cerebrovascular disease had a higher odds ratio (OR) of moderate-severe limitation at 2-years and 5-years, 1.32 (95% confidence interval [CI]: 1.02, 1.72; P=0.04) and 1.83 (95% CI: 1.32, 2.55; P<0.001). No significant associations were noted with moderate-severe pain at 2-years or 5-years. In conclusion, we found that cerebrovascular disease is independently associated with pain and function outcomes after primary TKA. This should be taken into consideration when discussing expected outcomes of TKA with patients.
Pain; Activity limitation; cerebrovascular disease; Total knee replacement; arthroplasty; joint replacement; outcomes; Patient-Reported Outcomes; Activities of Daily Living; ADLs; Function; functional limitation
Poor functional outcomes post knee replacement are common, but
estimates of its prevalence vary, likely in part because of differences in
methods used to assess function. The agreement between improvement in
function and absolute good levels of function after knee replacement has not
been evaluated. We evaluated the attainment of improvement in function and
absolute good function after total knee replacement (TKR) and the agreement
between these measures.
Using data from The Multicenter Osteoarthritis (MOST) Study, we
determined the prevalence of achieving a minimal clinically important
improvement (MCII, ≥ 14.2/68 point improvement) and Patient
Acceptable Symptom State (PASS, ≤ 22/68 post-TKR score) on the
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
Physical Function subscale at least 6 months after knee replacement. We also
assessed the frequency of co-occurrence of the 2 outcomes, and the
prevalence according to pre-knee replacement functional status.
We included 228 subjects who had a knee replacement during followup
(mean age 65 yrs, mean body mass index 33.4,73% female). Seventy-one
percent attained the PASS for function after knee replacement, while only
44% attained the MCII. Of the subjects who met the MCII, 93%
also attained the PASS; however, of subjects who did not meet the MCII,
54% still achieved a PASS. Baseline functional status was associated
with attainment of each MCII and PASS.
There was only partial overlap between attainment of a good level of
function and actually improving by an acceptable amount. Subjects were more
likely to attain an acceptable level of function than to achieve a
clinically important amount of improvement post knee replacement.
Single-item assessments have been the most often-used measures in National Cancer Institute (NCI) cancer control clinical trials, but normative data are not available. Our objective was to examine the normative data and clinically significant effect sizes for single-item numerical linear analogue self-assessment (LASA) scale for overall quality of life (QOL).
We analyzed baseline data from 36 clinical trials and 6 observational studies with various populations, including healthy volunteers, cancer trial patients (patients with advanced incurable cancer or patients receiving treatment with curative intent) and hospice patients as well as their caregivers. The overall QOL LASA was rated 0 (as bad as it can be) to 10 (as good as it can be). We calculated the summary statistics and the proportion of patients reporting a clinically meaningful deficit (CMD) of a score equal to 5 or less on the 0–10 scale.
In total, for the collective sample of 9,295 individuals, the average overall QOL reported was 7.39 (SD = 2.11) with a markedly skewed distribution with roughly 17% reporting a score of 5 or below indicating a clinically significant deficit in overall QOL. Hospice patients report a much worse average score of 5.7 upon entry to hospice; hospice caregivers average 7.4. Cancer patients vary within these two extremes with most patients averaging in the 7’s on the 0–10 scale (range, 0 to 10 p-value < 0.0001). Men and women’s QOL distributions were virtually identical (with average of 7.6 vs. 7.5, p-value = 0.046). Overall QOL was weakly related to performance status with a Spearman correlation coefficient of −0.29 (p-value < 0.0001). Overall QOL was related to tumor response (p-value = 0.0094), i.e. patients with a full or partial response reported a CMD in 11.4% of cases compared to 14.4% among those with stable disease and 18.5% among those with disease progression. Data missingness was high for performance status and tumor response associations.
This study provides the normative data for cancer patients and healthy volunteers for overall QOL using the LASA. These can serve as benchmarks for future studies and inform clinical practice decision-making.
Electronic supplementary material
The online version of this article (doi:10.1186/s12955-014-0187-z) contains supplementary material, which is available to authorized users.
Quality of life; Measurement; LASA; Validation; Single item; Linear analog scale; Patient-reported outcomes; PROs; QOL
To examine whether function and pain outcomes of patients undergoing primary total knee arthroplasty (TKA) are changing over time.
The Mayo Clinic Total Joint Registry provided data for time-trends in preoperative and 2-year post-operative activity limitation and pain in primary TKA patients from 1993-2005. We used chi-square test and analysis for variance, as appropriate. Multivariable-adjusted analyses were done using logistic regression.
In a cohort of 7,229 patients who underwent primary TKA during 1993-2005, mean age was 68.4 years (standard deviation (SD), 9.8), mean BMI was 31.1 (SD, 6.0) and 55% were women. Crude estimates showed that preoperative moderate-severe overall limitation were seen in 7.3% fewer patients and preoperative moderate-severe pain in 2.7% more patients in 2002-05, compared to 1992-95 (p < 0.001 for both). At 2-years, crude estimates indicated that compared to 1992-95, moderate-severe post-TKA overall limitation was seen in 4.7% more patients and moderate-severe post-TKA pain in 3.6% more patients in 2002-05, both statistically significant (p ≤ 0.018) and clinically meaningful. In multivariable-adjusted analyses that adjusted for age, sex, anxiety, depression, Deyo-Charlson index, body mass index and preoperative pain/limitation, patients had worse outcomes 2-year post-TKA in 2002-2005 compared to 1993-95 with an odds ratio (95% confidence interval (CI); p-value) of 1.34 (95% CI: 1.02, 1.76, p = 0.037) for moderate-severe activity limitation and 1.79 (95% CI: 1.17, 2.75, p = 0.007) for moderate-severe pain.
Patient-reported function and pain outcomes after primary TKA have worsened over the study period 1993-95 to 2002-05. This time-trend is independent of changes in preoperative pain/limitation and certain patient characteristics.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2474-15-440) contains supplementary material, which is available to authorized users.
Total knee replacement; Time trends; Arthroplasty; Joint replacement; Pain; Function
Few, if any data are available are available regarding the time-trends in characteristics of patients who have undergone primary THA. Our objective was to examine the time-trends in key demographic and clinical characteristics of patients undergoing primary total hip arthroplasty (THA).
We used the data from the Mayo Clinic Total Joint Registry from 1993–2005 to examine the time-trends in demographics (age, body mass index (BMI)), medical (Deyo-Charlson index) and psychological comorbidity (anxiety, depression) and underlying diagnosis of patients undergoing primary THA. Chi-square test and analysis for variance were used. Multivariable-adjusted logistic regression (age, sex, comorbidity-adjusted) compared 1993–95 to other study periods. Odds ratio (OR) and 95% confidence interval (CI) are presented.
The primary THA cohort consisted of 6,168 patients with 52% women. In unadjusted analyses, compared to 1993–95, significantly more patients (by >2-times for most) in 2002–05 had: BMI ≥ 40, 2.3% vs. 6.3%; depression, 4.1% vs. 9.8%; and anxiety, 3.4% vs. 5.7%; and significantly fewer had an underlying diagnosis of rheumatoid/inflammatory arthritis, 3.7% vs. 1.5% (p ≤ 0.01 for all). In multivariable-adjusted models, compared to 1993–95, significantly more patients in 2003–05 had (all p-values ≤ 0.01): BMI ≥ 40, OR, 2.79 (95% CI: 1.85, 4.22); Deyo-Charlson Index ≥ 3, 1.32 (1.07, 1.63); depression, 2.25 (1.66, 3.05); and anxiety, 1.71 (1.19, 2.15). Respectively, fewer patients had a diagnosis of RA/inflammatory arthritis: 0.28 (0.17, 0.46; p < 0.01). Over the 13-year study period, Deyo-Charlson index increased by 22% (0.9 to 1.1) and the mean age decreased by 0.7 years (65.0 to 64.3) (p < 0.01 for both).
Obesity, medical and psychological comorbidity increased and the underlying diagnosis of RA/inflammatory arthritis decreased rapidly in primary THA patients over 13-years. Our cohort characteristics are similar to previously described characteristics of national U.S. cohort, suggesting that these trends may be national rather than local trends. This is important information for policy makers to take into account for resource allocation. Studies of THA outcomes and utilization should take these rapidly changing patient characteristics into account.
Total hip replacement; Time trends; Arthroplasty; Joint replacement; Diagnosis; Obesity; Comorbidity; Osteoarthritis
The possible negative effects of smoking on postoperative outcomes have not been well-studied in cancer patients.
We used the VA Surgical Quality Improvement Program (VASQIP) database for the years 2002–2008, which assesses pre-operative risk factors and post-operative outcomes for patients undergoing major surgery within the VA healthcare system.
Compared to never smokers, prior smokers and current smokers with GI malignancies were significantly more likely to have surgical site infection (SSI)( Odds ratio, OR:1.25, 95%CI:1.09–1.44)(OR:1.20, 95%CI:1.05–1.38), combined pulmonary complications (CPO: pneumonia, failure to wean from ventilator, reintubation) (OR:1.60, 95%CI:1.38–1.87)(OR:1.96, 95%CI:1.68–2.29) and return to the operating room (OR:1.20, 95%CI:1.03–1.39)(OR:1.31 95%CI:1.13–1.53), respectively. Both prior and current smokers had a significantly higher mortality at 30 days (OR:1.50, 95%CI:1.19–1.89)(OR: 1.41, 95%CI:1.08–1.82) and one year (OR:1.22, 95%CI:1.08–1.38)(OR:1.62, 95%C I:1.43–1.85). Thoracic surgery patients who were current smokers were more likely to develop CPO (OR:1.62, 95%CI:1.25–2.11), and mortality within one year (OR:1.50, 95%CI:1.17–1.92) compared to non-smokers, but SSI rates were not affected by smoking status. Current smokers had a significant increase in postsurgical length of stay (overall 4.3% [p<0.001], GI 4.7% [p=0.003], thoracic 9.0% [p<0.001]) compared to prior smokers.
Prior and current smoking status is a significant risk factor for major postoperative complications and mortality following GI cancer and thoracic operations in veterans. Smoking cessation should be encouraged prior to all major cancer surgery in the VA population to decrease postoperative complications and length of stay.
Smoking; Cancer; Surgery outcomes; Postoperative complications
To perform a systematic review of 30- and 90-day mortality rates in patients undergoing hip or knee arthroplasties.
Five databases were searched for English-language studies of mortality in hip or knee arthroplasties and the following data were extracted: patient characteristics (age, gender, ethnicity), arthroplasty characteristics (unilateral vs bilateral, hip vs knee), system factors (hospital volume and surgeon volume), year of study, etc… Mortality rates were compared across variable categories; proportions were compared using relative risk ratios and 95% confidence intervals.
Out of 650 titles and abstracts, 80 studies qualified for data inclusion. 35%, 34% and 31% studies provided 30-, 90- and >90-day mortality rates. Overall 30-day mortality rates published across all types of arthroplasties were 0.3%, 90-day: 0.7%. For those reports with specific rates, 30-day mortality was significantly higher in men than women (1.8% vs 0.4%; relative risk (RR): 3.93, 95% confidence interval (CI), 3.30–4.68) and bilateral vs unilateral procedures (0.5% vs 0.3%; RR, 1.6, 95% CI:1.49–1.72), but no differences were noted by the underlying diagnosis of osteoarthritis vs rheumatoid arthritis (0.4% vs 0.3%; RR 0.77, 95% CI:0.48–1.24). 90-day mortality showed non-significant trends favoring women, osteoarthritis as the underlying diagnosis, and unilateral procedures.
Several demographic and surgical factors were associated with higher 30-day mortality rates following knee and hip arthroplasties. More studies are needed to examine the effect of body mass index, comorbidities, and other modifiable factors, in order to identify interventions designed to lower mortality rates following arthroplasty procedures.
Mortality; Total Knee Arthroplasty; Total Hip Arthroplasty; Short-term mortality
The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100 000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.
We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990–2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.
292 982 (95% UI 261 017–327 792) maternal deaths occurred in 2013, compared with 376 034 (343 483–407 574) in 1990. The global annual rate of change in the MMR was −0·3% (−1·1 to 0·6) from 1990 to 2003, and −2·7% (−3·9 to −1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290–2866) maternal deaths were related to HIV in 2013, 0·4% (0·2–0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1–1262·8) in South Sudan to 2·4 (1·6–3·6) in Iceland.
Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.
Bill & Melinda Gates Foundation.
Examine whether racial disparities in utilization and outcomes of total knee and total hip arthroplasty (TKA and THA) have declined over time.
We used 1991-2008 Medicare Part A (MedPAR) data to identify four separate cohorts of patients (primary TKA, revision TKA, primary THA, revision THA). For each cohort, we calculated standardized arthroplasty utilization rates for White and Black Medicare beneficiaries for each calendar year and examined changes in disparities over time. We examined unadjusted and adjusted arthroplasty outcomes (30-day readmission rate, discharge disposition etc.) for Whites and Blacks and whether disparities decreased over time.
In 1991 utilization of primary TKA was 36% lower for Blacks compared to Whites (20.6 per 10,000 for Blacks; 32.1 per 10,000 for Whites; p<0.0001); in 2008 utilization of primary TKA for Blacks was 40% lower for Blacks (41.5 per 10,000 for Blacks; 68.8 per 10,000 for Whites; p<0.0001) with similar findings for the other cohorts. Black-White disparities in 30-day hospital readmission increased significantly from 1991-2008 among three patient cohorts. For example in 1991 30-day readmission rates for Blacks receiving primary TKA were 6% higher than for Whites; by 2008 readmission rates for Blacks were 24% higher (p<0.05 for change in disparity). Similarly, Black-White disparities in the proportion of patients discharged-to-home after surgery increased across the study period for all cohorts (p<0.05).
In an 18-year analysis of Medicare data we found little evidence of declines in racial disparities for joint arthroplasty utilization or outcomes.
Gout is one of the most common forms of arthritis. It is well established that urate lowering therapy that aims for a serum urate less than at least 0.36mmol/l (6mg/dL) is required for successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor is the most commonly used urate lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol, these patients can be considered to have “inadequate response” to allopurinol. Herein we examine the potential mechanisms and implications of inadequate response to allopurinol.
The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol.
The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be “partially resistant” to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and or function such that oxypurinol is rendered less effective, and/or drug interactions.
It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician toward making a therapeutic choice that is more likely to result in achieving the serum urate target.
The OMERACT Filter provides a framework for the validation of outcome measures for use in rheumatology clinical research. However, imaging and biochemical measures may face additional validation challenges due to their technical nature. The Imaging and Soluble Biomarker Session at OMERACT 11 aimed to provide a guide for the iterative development of an imaging or biochemical measurement instrument so it can be used in therapeutic assessment.
A hierarchical structure was proposed, reflecting 3 dimensions needed for validating an imaging or biochemical measurement instrument: outcome domain(s), study setting and performance of the instrument. Movement along the axes in any dimension reflects increasing validation. For a given test instrument, the 3-axis structure assesses the extent to which the instrument is a validated measure for the chosen domain, whether it assesses a patient or disease centred-variable, and whether its technical performance is adequate in the context of its application. Some currently used imaging and soluble biomarkers for rheumatoid arthritis, spondyloarthritis and knee osteoarthritis were then evaluated using the original OMERACT filter and the newly proposed structure. Break-out groups critically reviewed the extent to which the candidate biomarkers complied with the proposed step-wise approach, as a way of examining the utility of the proposed 3 dimensional structure.
Although there was a broad acceptance of the value of the proposed structure in general, some areas for improvement were suggested including clarification of criteria for achieving a certain level of validation and how to deal with extension of the structure to areas beyond clinical trials.
General support was obtained for a proposed tri-axis structure to assess validation of imaging and soluble biomarkers; nevertheless, additional work is required to better evaluate its place within the OMERACT Filter 2.0.
biomarkers; imaging; OMERACT filter; validation framework
The OMERACT Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The ‘Truth’ section of the OMERACT Filter pre-supposes an explicit framework for identifying the relevant core outcomes that are universal to all studies of the effects of intervention effects. There is no published outline for instrument choice or development that is aimed at measuring outcome, was derived from broad consensus over its underlying philosophy, or includes a structured and documented critique. Therefore, a new proposal for defining core areas of measurement (“Filter 2.0 Core Areas of Measurement”) was presented at OMERACT 11 to explore areas of consensus and consider whether already endorsed core outcome sets fit in to this newly proposed framework.
Discussion groups critically reviewed the extent to which case studies of current OMERACT Working Groups complied with or negated the proposed framework, whether these observations had a more general application, and what issues remained to be resolved.
Although there was a broad acceptance of the framework in general, several important areas of construction, presentation and clarity of the framework were questioned. The discussion groups and subsequent feedback highlighted 20 such issues.
These issues will require resolution in order to reach consensus on accepting the proposed Filter 2.0 framework of Core Areas as the basis for the selection of Core Outcome Domains and hence appropriate Core Outcome Sets for clinical trials.
Five core domains have been endorsed by Outcomes Measures in Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness, patient global assessment, and activity limitation. The aim of this work was to evaluate instruments for these domains according to the OMERACT filter: truth, feasibility, and discrimination.
A systematic search strategy for instruments used to measure the acute gout core domains was formulated. For each method, articles were assessed by two reviewers to summarise information according to the specific components of the OMERACT filter.
Seventy-seven articles and abstracts met the inclusion criteria. Pain was most frequently reported (76 studies, 20 instruments). The pain instruments used most often were 100mm visual analog scale (VAS) and 5-point Likert scale. Both methods have high feasibility, face and content validity, within- and between-group discrimination. Four-point Likert scales assessing index joint swelling and tenderness have been used in numerous acute gout studies; these instruments are feasible, with high face and content validity, and show within- and between-group discrimination. Five-point patient global assessment of response to treatment (PGART) scales are feasible and valid, and show within- and between-group discrimination. Measures of activity limitations were infrequently reported, and insufficient data were available to make definite assessments of the instruments for this domain.
Many different instruments have been used to assess the acute gout core domains. Pain VAS and 5-point Likert scales, 4-point Likert scales of index joint swelling and tenderness and 5-point PGART instruments meet the criteria for the OMERACT filter.
gout; pain; measurement; outcome
The OMERACT Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The ‘Truth’ section of the OMERACT Filter requires that criteria be met to demonstrate that the outcome instrument meets the criteria for content, face and construct validity.
Discussion groups critically reviewed the variety of ways in which case studies of current OMERACT Working Groups complied with the ‘Truth’ component of the Filter and what issues remained to be resolved.
The case studies showed that there is broad agreement on criteria for meeting the ‘Truth’ criteria through demonstration of content, face and construct validity; however several issues were identified that the Filter Working Group will need to address.
These issues will require resolution in order to reach consensus on how ‘Truth’ will be assessed for the proposed Filter 2.0 framework, for instruments to be endorsed by OMERACT.
To determine the extent to which instruments that measure core outcome domains in acute gout fulfil the OMERACT filter requirements of truth, discrimination and feasibility.
Patient-level data from four randomised controlled trials of agents designed to treat acute gout and one observational study of acute gout were analysed. For each available measure construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic and repeated measures generalised estimating equations were assessed. Floor and ceiling effects were also assessed and MCID was estimated. These analyses were presented to participants at OMERACT 11 to help inform voting for possible endorsement.
There was evidence for construct validity and discriminative ability for 3 measures of pain (0 to 4 Likert, 0 to 10 numeric rating scale, 0 to 100 mm visual analogue scale). Likewise, there appears to be sufficient evidence for a 4-point Likert scale to possess construct validity and discriminative ability for physician assessment of joint swelling and joint tenderness. There was some evidence for construct validity and within-group discriminative ability for the Health Assessment Questionnaire as a measure of activity limitations, but not for discrimination between groups allocated to different treatment.
There is sufficient evidence to support measures of pain (using Likert, numeric rating scale or visual analogue scales), joint tenderness and swelling (using Likert scale) as fulfilling the requirements of the OMERACT filter. Further research on a measure of activity limitations in acute gout clinical trials is required.
gout; outcome measures; psychometrics
It is unknown whether previously reported disparities for acute myocardial infarction (AMI) by race and sex have declined over time.
We used Medicare Part A administrative data files for 1992 to 2010 to evaluate changes in per-capita hospitalization rates for AMI, rates of revascularization (percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)), and 30-day mortality for four distinct patient subcohorts: black women; black men; white women; and white men, adjusted for age, comorbidities and year using logistic regression.
The study sample consisted of 4,045,267 AMI admissions between the years 1992 and 2010 (166,660 black women; 116,201 black men; 1,870,816 white women; 1,891,590 white men). AMI hospitalization rates differed significantly in 1992 to 1993 among black women (61.6 hospitalizations per 10,000 Medicare enrollees), black men (73.2 hospitalizations), white women (72.0 hospitalizations) and white men (113.2 hospitalizations) (P <0.0001). By 2009 to 2010 AMI hospitalization rates had declined substantially in all cohorts but disparities remained with significantly lower hospitalization rates among women and blacks compared to men and whites, respectively (P <0.0001). In multivariable-adjusted analyses, despite narrowing of the differences between cohorts over time, disparities in AMI hospitalization rates by race and sex remained statistically significant in 2009 to 2010 (P <0.001). In 1992 to 1993 and 2009 to 2010, rates of PCI within 30-days of AMI differed significantly among black women (8.6% in 1992 to 1993; 24.2% in 2009 to 2010), black men (10.4% and 32.6%), white women (12.8% and 30.5%), and white men (16.1% and 40.7%) (P <0.0001). In multivariable-adjusted analyses, racial disparities in procedure utilization appeared somewhat larger and sex-based disparities remained significant. Unadjusted 30-day mortality after AMI in 1992 to 1993 for black women, black men, white women and white men was 20.4%, 17.9%, 23.1% and 19.5%, respectively (P <0.0001); in 2009 to 2010 mortality was 17.1%, 15.3%, 18.2% and 16.2%, respectively (P <0.0001). In adjusted analyses, racial differences in mortality declined over time but differences by sex (higher mortality for women) persisted.
Disparities in AMI have declined modestly, but remain a problem, particularly with respect to patient sex.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0190-6) contains supplementary material, which is available to authorized users.
Myocardial infarction; MI; Disparity; Outcomes; Race; Sex; Mortality; PCI; Hospitalization rates
The forthcoming post-Millennium Development Goals era will bring about new challenges in global health. Low- and middle-income countries will have to contend with a dual burden of infectious and non-communicable diseases (NCDs). Some of these NCDs, such as neoplasms, COPD, cardiovascular diseases and diabetes, cause much health loss worldwide and are already widely recognised as doing so. However, 55% of the global NCD burden arises from other NCDs, which tend to be ignored in terms of premature mortality and quality of life reduction. Here, experts in some of these ‘forgotten NCDs’ review the clinical impact of these diseases along with the consequences of their ignoring their medical importance, and discuss ways in which they can be given higher global health priority in order to decrease the growing burden of disease and disability.
Global health; Non-communicable diseases; Sickle cell disease; Chronic kidney disease; Asthma; Dementia; Gout; Substance abuse; Alcohol; Liver cirrhosis
The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occurred since the Millennium Declaration.
To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010–13) of incidence, drug resistance, and coverage of insecticide-treated bednets.
Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.
Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS’s estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.
Bill & Melinda Gates Foundation.
There is compelling evidence of a genetic foundation of patient-reported QOL. Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010.
The objective is to provide an updated overview of the biological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL.
We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains.
Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL.
Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL.
biological pathways; genes; molecular markers; quality of life; patient-reported outcomes (PROs)
The impact of knee arthroplasty on subsequent body weight gain has not been fully explored. Clinically important weight gain following knee arthroplasty would pose potentially important health risks.
We used one of the largest US-based knee arthroplasty registries and a population- based control sample from the same geographic region to determine whether knee arthroplasty increases risk of clinically important weight gain of 5% or more of baseline body weight over a 5-year postoperative period.
Of the persons in the knee arthroplasty sample, 30.0% gained 5% or more of baseline body weight five years following surgery as compared to 19.7% of the control sample. The multivariable adjusted (age, sex, BMI, education, comorbidity and pre-surgical weight change) odds ratio was 1.6 (95% CI, 1.2, 2.2) in persons with knee arthroplasty as compared to the control sample. Additional arthroplasty procedures during the 5-year follow-up further increased risk for weight gain (OR=2.1, 95% CI, 1.4, 3.1) relative to the control sample. Specifically among patients with knee arthroplasty, younger patients and those who lost greater amounts of weight in the 5-year pre-operative period were at greater risk for clinically important weight gain.
Patients who undergo knee arthroplasty are at increased risk of clinically important weight gain following surgery. Future research should develop weight loss/maintenance interventions particularly for younger patients who have lost a substantial amount of weight prior to surgery as they are most at risk for substantial postsurgical weight gain.
Gout; gouty arthritis; patient; nominal group; NGT; treatment; medication
Gout; gouty arthritis; research priorities; patient; nominal group; NGT; diet; supplements
Total Knee Arthroplasty (TKA) is one of the most common and costly surgical procedures performed in the United States (U.S.).
To examine longitudinal trends in volume, utilization and outcomes for primary and revision TKA between 1991 and 2010 in the U.S. Medicare population.
Design, Setting, and Participants
Observational cohort of 3,271,851 patients who underwent primary TKA and 318,563 who underwent revision TKA identified in Medicare Part A data files.
We examined changes in primary and revision TKA volume, per-capita utilization, hospital length of stay (LOS), readmission rates, and adverse outcomes.
Between 1991 and 2010 annual primary TKA volume increased 161.5% from 93,230 to 226,177 while per-capita utilization increased 99.2%. Revision TKA volume increased 105.9% from 9,650 to 19,871 while utilization increased 56.8%. For primary TKA, LOS decreased from 7.9 days (95% CI, 7.8–7.9) in 1991–1994 to 3.5 days (95% CI, 3.5-3.5) in 2007–2010 (P< 0.001). For primary TKA rates of adverse outcomes resulting in readmission remained stable between 1991–2010, but rates of all-cause 30-day readmission increased from 4.2% (95% CI, 4.1–4.2) to 5.0% (95% CI, 4.9–5.0) (P<0.001). For revision TKA, the decline in hospital LOS was accompanied by an increase in 30-day readmission from 6.1% (95% CI, 5.9–6.4) to 8.9% (95% CI, 8.7–9.2) (P<.001) and an increase in wound infection rates from 1.4% (95% CI, 1.3–1.5) to 3.0% (95% CI, 2.9–3.1) (P<.001).
Increases in TKA volume have largely been driven by increases in per-capita utilization. We also observed decreases in hospital LOS that were accompanied by increases in hospital readmission rates.
Literature examining the effects of total hip arthroplasty (THA) on subsequent body weight gain is inconclusive. Determining the extent to which clinically relevant weight gain occurs following THA has important public health implications.
We used multivariable logistic regression to compare data from one of the largest US-based THA registries to a population-based control sample from the same geographic region. We also identified factors that increased risk of clinically important weight gain specifically among persons undergoing THA. The outcome measure of interest was weight gain of ≥ 5% of body weight up to 5 years following surgery.
The multivariable adjusted (age, sex, BMI, education, comorbidity and pre-surgical weight change) odds ratio for important weight gain was 1.7 (95% CI, 1.06, 2.6) for a person with THA as compared the control sample. Additional arthroplasty procedures during the 5-year follow-up further increased odds for important weight gain (OR=2.0, 95% CI, 1.4, 2.7) relative to the control sample. A patient with THA had increased risk of important post-surgical weight gain of 12% (OR=1.12; 95%CI,1.08, 1.16) for every kilogram of pre-operative weight loss.
While findings should be interpreted with caution because of missing follow-up weight data, patients with THA appear to be at increased risk of clinically important weight gain following surgery as compared to peers. Patients less than 60 years and who have lost a substantial amount of weight prior to surgery appear to be at particularly high risk of important postsurgical weight gain.
knee; hip; arthroplasty; obesity