Max Gordon

Snapshot of Moving and Expanding Clones of Mycobacterium tuberculosis and Their Global Distribution Assessed by Spoligotyping in an International Study

ABSTRACT The present update on the global distribution of Mycobacterium tuberculosis complex spoligotypes provides both the octal and binary descriptions of the spoligotypes for M. tuberculosis complex, including Mycobacterium bovis, from >90 countries (13,008 patterns grouped into 813 shared types containing 11,708 isolates and 1,300 orphan patterns). A number of potential indices were developed to summarize the information on the biogeographical specificity of a given shared type, as well as its geographical spreading (matching code and spreading index, respectively). To facilitate the analysis of hundreds of spoligotypes each made up of a binary succession of 43 bits of information, a number of major and minor visual rules were also defined. A total of six major rules (A to F) with the precise description of the extra missing spacers (minor rules) were used to define 36 major clades (or families) of M. tuberculosis. Some major clades identified were the East African-Indian (EAI) clade, the Beijing clade, the Haarlem clade, the Latin American and Mediterranean (LAM) clade, the Central Asian (CAS) clade, a European clade of IS6110 low banders (X; highly prevalent in the United States and United Kingdom), and a widespread yet poorly defined clade (T). When the visual rules defined above were used for an automated labeling of the 813 shared types to define nine superfamilies of strains (Mycobacterium africanum, Beijing, M. bovis, EAI, CAS, T, Haarlem, X, and LAM), 96.9% of the shared types received a label, showing the potential for automated labeling of M. tuberculosis families in well-defined phylogeographical families. Intercontinental matches of shared types among eight continents and subcontinents (Africa, North America, Central America, South America, Europe, the Middle East and Central Asia, and the Far East) are analyzed and discussed.

Global Distribution of Mycobacterium tuberculosis Spoligotypes

We present a short summary of recent observations on the global distribution of the major clades of the Mycobacterium tuberculosis complex, the causative agent of tuberculosis. This global distribution was defined by data-mining of an international spoligotyping database, SpolDB3. This database contains 11,708 patterns from as many clinical isolates originating from more than 90 countries. The 11,708 spoligotypes were clustered into 813 shared types. A total of 1,300 orphan patterns (clinical isolates showing a unique spoligotype) were also detected.

Projections of total hip replacement in Sweden from 2013 to 2030

Background and purpose — The continuously increasing demand for joint replacement surgery in the past decades imposes higher constraints on the budgets of hospitals and healthcare providers. We undertook an analysis of historical trends in total hip replacement performed in Sweden between 1968 and 2012 in order to provide projections of future demand. Data and methods — We obtained data on total hip replacements registered every year and on the evolution of the Swedish population between 1968 and 2012. We assumed the existence of a maximum incidence. So we adopted a regression framework that assumes the existence of an upper limit of total hip replacement incidence. Results — We found that the incidence of total hip replacement will continue to increase until a projected upper incidence level of about 400 total hip replacements per 105 Swedish residents aged 40 years and older will be reached around the year 2107. In 2020, the estimated incidence of total hip replacement will be 341 (95% prediction interval (PI): 302–375) and in 2030 it will be 358 (PI: 317–396). Using official forecasted population growth data, about 18,000 operations would be expected to be performed in 2020 and 20,000 would be expected to be performed in 2030. Interpretation — Growing incidence, population growth, and increasing life expectancy will probably result in increased demand for hip replacement surgery. Our findings could serve as a basis for decision making.

Molecular Epidemiology of Mycobacterium tuberculosis in Western Sweden

ABSTRACT The genetic diversity of Mycobacterium tuberculosis isolates among patients from Sweden was determined by a combination of two PCR-based techniques (spoligotyping and variable number of tandem repeats analysis). It resulted in a clustering of 23.6% of the isolates and a rate of recent transmission of 14.1%. The clustered isolates mainly belonged to the Haarlem family (23.2%), followed by the Beijing (9.8%), Latin American and Mediterranean (LAM; 8%), and East African-Indian (EAI; 6.2%) families. A comparison of the spoligotypes with those in the international spoligotyping database showed that 62.5% of the clustered isolates and 36.6% of all isolates typed were grouped into six major shared types. A comparison of the spoligotypes with those in databases for Scandinavian countries showed that 33% of the isolates belonged to an ill-defined T family, followed by the EAI (22%), Haarlem (20%), LAM (11%), Central Asian (5%), X (5%), and Beijing (4%) families. Both the highest number of cases and the proportion of clustered cases were observed in patients ages 15 to 39 years. Nearly 10% of the isolates were resistant to one or more drugs (essentially limited to isoniazid monoresistance). However, none of the strains were multidrug resistant. Data on the geographic origins of the patients showed that more than two-thirds of the clustered patients with tuberculosis were foreign-born individuals or refugees. These results are explained on the basis of both the historical links within specific countries and recently imported cases of tuberculosis into Sweden.

The influence of comorbidity scores on re-operations following primary total hip replacement: Comparison and validation of three comorbidity measures

While an increasing amount of arthroplasty articles report comorbidity measures, none have been validated for outcomes. In this study, we compared commonly used International Classification of Diseases-based comorbidity measures with re-operation rates after total hip replacement (THR). Scores used included the Charlson, the Royal College of Surgeons Charlson, and the Elixhauser comorbidity score. We identified a nationwide cohort of 134 423 THRs from the Swedish Hip Arthroplasty Register. Re-operations were registered post-operatively for up to 12 years. The hazard ratio was estimated by Coxs proportional hazards regression, and we used C-statistics to assess each measures ability to predict re-operation. Confounding variables were age, gender, type of implant fixation, hospital category, hospital implant volume and year of surgery. In the first two years only the Elixhauser score showed any significant relationship with increased risk of re-operation, with increased scores for both one to two and three or more comorbidities. However, the predictive C-statistic in this period for the Elixhauser score was poor (0.52). None of the measures proved to be of any value between two and 12 years. They might be of value in large cohort or registry studies, but not for the individual patient.

Age- and health-related quality of life after total hip replacement: Decreasing gains in patients above 70 years of age

Background — While age is a common confounder, its impact on health-related quality of life (HRQoL) after total hip replacement is uncertain. This could be due to improper statistical modeling of age in previous studies, such as treating age as a linear variable or by using age categories. We hypothesized that there is a non-linear association between age and HRQoL. Methods — We selected a nationwide cohort from the Swedish Hip Arthroplasty Register of patients operated with total hip replacements due to primary osteoarthritis between 2008 and 2010. For estimating HRQoL, we used the generic health outcome questionnaire EQ-5D of the EuroQol group that consits or 2 parts: the EQ-5D index and the EQ VAS estimates. Using linear regression, we modeled the EQ-5D index and the EQ VAS against age 1 year after surgery. Instead of using a straight line for age, we applied a method called restricted cubic splines that allows the line to bend in a controlled manner. Confounding was controlled by adjusting for preoperative HRQoL, sex, previous contralateral hip surgery, pain, and Charnley classification. Results — Complete data on 27,245 patients were available for analysis. Both the EQ-5D index and EQ VAS showed a non-linear relationship with age. They were fairly unaffected by age until the patients were in their late sixties, after which age had a negative effect. Interpretation — There is a non-linear relationship between age and HRQoL, with improvement decreasing in the elderly.

Improved statistical analysis of pre- and post-treatment patient-reported outcome measures (PROMs): the applicability of piecewise linear regression splines

PurposePatient-reported health-related quality-of-life (HRQoL) measures such as the EuroQol 5 dimension (EQ-5D) index are commonplace when assessing healthcare providers or efficiency of medical techniques. HRQoL measures are generally bounded, and the magnitude of possible improvement depends on the pre-treatment HRQoL value. This paper aimed to assess and illustrated the possibility of modelling the relationship between pre- and post-treatment HRQoL measures with piecewise linear splines.MethodsThe method was illustrated using a longitudinal dataset of 36,625 patients with one EQ-5D index before and one a year after total hip arthroplasty. We considered four models: intercept only model, single line regression, and segmented regression with 1 and 2 change points. The post-operative EQ-5D index served as the outcome, while the preoperative EQ-5D index was the predictor.ResultsWe found that a two-line regression best described the data with the lines meeting at 0.159 on the preoperative EQ-5D index scale. In the low preoperative group (with an initial preoperative index from −0.594 to 0.159), the predicted post-operative scores ranged from 0.368 to 0.765, with post-operative scores increasing 0.528 points for each unit in the preoperative score. In the high preoperative group (initial range from 0.159 to 1), the predicted post-operative scores ranged from 0.765 to 0.855, increasing 0.106 points for each unit in the preoperative score.ConclusionsPiecewise linear regression is a straightforward approach to analyse baseline and follow-up HRQoL measures such as the EQ-5D index. It can provide a reasonable approximation of the shape of the underlying relationship where the threshold and slopes prove informative and meaningful.

Women in Charnley class C fail to improve in mobility to a higher degree after total hip replacement

Background— The Charnley comorbidity classification organizes patients into 3 classes: (A) 1 hip involved, (B) 2 hips involved, and (C) other severe comorbidities. Although this simple classification is a known predictor of health-related quality of life (HRQoL) after total hip replacement (THR), interactions between Charnley class, sex, and age have not been investigated and there is uncertainty regarding whether A and B should be grouped together. Methods — We selected a nationwide cohort of patients from the Swedish Hip Arthroplasty Register operated with THR due to primary osteoarthritis between 2008 and 2010. For estimation of HRQoL, we used the generic health outcome questionnaire EQ-5D of the EuroQol group. This consists of 2 parts: the EQ-5D index and the EQ VAS estimates. We modeled the EQ-5D index and the EQ VAS against the self-administered Charnley classification. Confounding was controlled for using preoperative HRQoL values, pain, and previous contralateral hip surgery. Results — We found that women in class C had a poorer EQ-5D outcome than men. This effect was mostly due to the fact that women failed to improve in the mobility dimension; only 40% improved, while about 50% of men improved. Age did not interact with Charnley class. We also found that the classification performed best without splitting or aggregating classes. Interpretation — Our results suggests that the self-administered Charnley classification should be used in its full capacity and that it may be interesting to devote special attention to women in Charnley class C.

Factors influencing health-related quality of life after total hip replacement--a comparison of data from the Swedish and Danish hip arthroplasty registers.

BackgroundThere is an increasing focus on measuring patient-reported outcomes (PROs) as part of routine medical practice, particularly in fields such as joint replacement surgery where pain relief and improvement in health-related quality of life (HRQoL) are primary outcomes. Between-country comparisons of PROs may present difficulties due to cultural differences and differences in the provision of health care. However, in order to understand how these differences affect PROs, common predictors for poor and good outcomes need to be investigated. This cross-sectional study investigates factors influencing health-related quality of life (HRQoL) one year after total hip replacement (THR) surgery in Sweden and in Denmark.MethodsData was retrieved from the Swedish (n = 14 560 patients) and Danish (n = 632 patients) Hip Arthroplasty Registers according to preset selection criteria. Using linear regression models, we examined how sex, age, comorbidity and country of surgery were associated with different aspects of HRQoL as measured by the EQ-5D index and EQ VAS.ResultsDanish patients had an overall higher EQ-5D index and EQ VAS than Swedish patients (p < 0.001). After regression analysis, the estimated coefficients for sex, age, or the Charlson score did not differ between countries for either the EQ-5D index (p = 0.83) or EQ VAS (p = 0.41) one year after THR.ConclusionsWe conclude that there are clear similarities in how basic predictors influence patient-reported outcomes (PROs) in patients with THR in Sweden and Denmark and these known predictors of good or poor HRQoL outcomes are not specific for each country.

Deep infection after total hip replacement: a method for national incidence surveillance.

OBJECTIVE The purpose of this study was to estimate the incidence of deep periprosthetic joint infections (PJIs) after primary total hip replacement (THR) in Sweden prior to the introduction of a national initiative to reduce these infections. DESIGN Prospective open cohort study with 2 years follow-up of each subject. SETTING All THR-performing clinics in Sweden. METHODS All patients registered for a primary THR in the Swedish Hip Arthroplasty Register between July 1, 2005, and December 31, 2008, were selected for the study (45,531 patients with 49,219 THRs) and were matched with the Swedish Prescribed Drug Register. All patients with a minimum of 4 weeks of continuous outpatient antibiotic treatment within 2 years after their primary THR (1,989 patients with 2,219 THRs) were selected for a medical records review, and the number of cases with PJI was determined. RESULTS The cumulative incidence of PJI within 2 years after primary THR was 0.9% (95% confidence interval, 0.85-1.02; n = 443), and 405 of these had been reoperated. The incidence rate of PJI for the first 3 months was 5 per 10,000 THR-weeks and, thereafter, 0.3 per 10,000 THR-weeks. Staphylococcus aureus and coagulase-negative staphylococci were the most common bacteria isolated. CONCLUSIONS This study describes a new method of national postoperative infection surveillance. The incidence is similar to previous smaller reports and is useful for monitoring changes over time to evaluate the national initiative to reduce infections.