Screening for Chlamydia trachomatis: a systematic review of the economic evaluations and modelling

OBJECTIVE: To review systematically and critically, evidence used to derive estimates of costs and cost effectiveness of chlamydia screening. METHODS: Systematic review. A search of 11 electronic bibliographic databases from the earliest date available to August 2004 using keywords including chlamydia, pelvic inflammatory disease, economic evaluation, and cost. We included studies of chlamydia screening in males and/or females over 14 years, including studies of diagnostic tests, contact tracing, and treatment as part of a screening programme. Outcomes included cases of chlamydia identified and major outcomes averted. We assessed methodological quality and the modelling approach used. RESULTS: Of 713 identified papers we included 57 formal economic evaluations and two cost studies. Most studies found chlamydia screening to be cost effective, partner notification to be an effective adjunct, and testing with nucleic acid amplification tests, and treatment with azithromycin to be cost effective. Methodological problems limited the validity of these findings: most studies used static models that are inappropriate for infectious diseases; restricted outcomes were used as a basis for policy recommendations; and high estimates of the probability of chlamydia associated complications might have overestimated cost effectiveness. Two high quality dynamic modelling studies found opportunistic screening to be cost effective but poor reporting or uncertainty about complication rates make interpretation difficult. CONCLUSION: The inappropriate use of static models to study interventions to prevent a communicable disease means that uncertainty remains about whether chlamydia screening programmes are cost effective or not. The results of this review can be used by health service managers in the allocation of resources, and health economists and other researchers who are considering further research in this area.

The Design and Analysis of Partner Studies of HIV Transmission

Common goals in epidemiologic studies of infectious diseases include identification of the infectious agent, description of the modes of transmission and characterization of factors that influence the probability of transmission from infected to uninfected individuals. In the case of AIDS, the agent has been identified as the Human Immunodeficiency Virus (HIV), and transmission is known to occur through a variety of contact mechanisms including unprotected sexual intercourse, transfusion of infected blood products and sharing of needles in intravenous drug use. Relatively little is known about the probability of IV transmission associated with the various modes of contact, or the role that other cofactors play in promoting or suppressing transmission. Here, transmission probability refers to the probability that the virus is transmitted to a susceptible individual following exposure consisting of a series of potentially infectious contacts. The infectivity of HIV for a given route of transmission is defined to be the per contact probability of infection. Knowledge of infectivity and its relationship to other factors is important in understanding the dynamics of the AIDS epidemic and in suggesting appropriate measures to control its spread. The primary source of empirical data about infectivity comes from sexual partners of infected individuals. Partner studies consist of a series of such partnerships, usually heterosexual and monogamous, each composed of an initially infected "index case" and a partner who may or may not be infected by the time of data collection. However, because the infection times of both partners may be unknown and the history of contacts uncertain, any quantitative characterization of infectivity is extremely difficult. Thus, most statistical analyses of partner study data involve the simplifying assumption that infectivity is a constant common to all partnerships. The major objectives of this work are to describe and discuss the design and analysis of partner studies, providing a general statistical framework for investigations of infectivity and risk factors for HIV transmission. The development is largely based on three papers: Jewell and Shiboski (1990), Kim and Lagakos (1990), and Shiboski and Jewell (1992).

Cementless hemiarthroplasty in femoral neck fractures: evaluation of clinical results and measurement of migration by EBRA-FCA

Aim of the present study was to evaluate migration rates of cementless primary hemiarthroplasty in acute femoral neck fractures. In a longitudinal, prospective study 46 patients were treated by cementless hemiarthroplasty. Clinical follow up was correlated with the EBRA-FCA method. In 30% of all patients stem migration amounted to more than 2 mm; further, these patients were seen to have a high level of activity. A high degree of migration in more than 30% of all patients requires critical scepticism toward further use of the investigated cementless stem as hemiarthroplasty. According to literature, migration of more than 2 mm suggests a high probability of early aseptic loosening. In patients with a low degree of activity good results could be observed; nevertheless, in patients with a high level of activity the combination of the investigated cementless stem with a solid fracture head cannot be recommended.

Influence of secondary infection on amputation in chronic critical limb ischemia

OBJECTIVES: To evaluate the influence of secondary infection on major amputation in chronic critical leg ischemia (CLI). DESIGN: Prospective, controlled observational study. MATERIALS AND METHODS: Sixty-seven patients with CLI and ischemic lesions participated in the study. Presence of infection was defined by clinical, laboratory and radiological criteria. Patients were categorized as having no local infection, soft tissue infection or osteomyelitis treated without antibiotics, amoxicillin/clavulanacid for 1 month or ciprofloxacin and clindamycin for 3 months, respectively. Clinical outcome was assessed at 2, 6 and 12 months. Study endpoints were major amputation and mortality. Analyses were performed using the Kaplan-Meier method. RESULTS: Forty-seven of 67 patients had a local infection. Major amputation was lower in patients with successful revascularization as compared to patients unsuitable for or with failed (without) revascularization (0% vs 26%, p<0.01). In patients with successful revascularization the probability of complete healing was lower with secondary infection (23% vs 71%, p=0.03). In patients without revascularization complete healing was rare (<10%), but secondary infection did not influenced major amputation, mortality or serious adverse events. CONCLUSION: Secondary infection reduces the likelihood of successful healing following revascularisation of CLI.

Microbial colonization patterns predict the outcomes of surgical treatment of intrabony defects

AIM: To explore the impact of bacterial load and microbial colonization patterns on the clinical outcomes of periodontal surgery at deep intrabony defects. MATERIALS AND METHODS: One hundred and twenty-two patients with advanced chronic periodontitis and at least one intrabony defect of >3 mm were recruited in 10 centres. Before recruitment, the infection control phase of periodontal therapy was completed. After surgical access and debridement, the regenerative material was applied in the test subjects, and omitted in the controls. At baseline and 1 year following the interventions, clinical attachment levels (CAL), pocket probing depths (PPD), recession (REC), full-mouth plaque scores and full-mouth bleeding scores were assessed. Microbial colonization of the defect-associated pocket was assessed using a DNA-DNA checkerboard analysis. RESULTS: Total bacterial load and counts of red complex bacteria were negatively associated with CAL gains 1 year following treatment. The probability of achieving above median CAL gains (>3 mm) was significantly decreased by higher total bacterial counts, higher red complex and T. forsythensis counts immediately before surgery. CONCLUSIONS: Presence of high bacterial load and specific periodontal pathogen complexes in deep periodontal pockets associated with intrabony defects had a significant negative impact on the 1 year outcome of surgical/regenerative treatment.

ASSESSING THE UNRELIABILITY OF THE MEDICAL LITERATURE: A RESPONSE TO "WHY MOST PUBLISHED RESEARCH FINDINGS ARE FALSE"

A recent article in this journal (Ioannidis JP (2005) Why most published research findings are false. PLoS Med 2: e124) argued that more than half of published research findings in the medical literature are false. In this commentary, we examine the structure of that argument, and show that it has three basic components: 1)An assumption that the prior probability of most hypotheses explored in medical research is below 50%. 2)Dichotomization of P-values at the 0.05 level and introduction of a “bias” factor (produced by significance-seeking), the combination of which severely weakens the evidence provided by every design. 3)Use of Bayes theorem to show that, in the face of weak evidence, hypotheses with low prior probabilities cannot have posterior probabilities over 50%. Thus, the claim is based on a priori assumptions that most tested hypotheses are likely to be false, and then the inferential model used makes it impossible for evidence from any study to overcome this handicap. We focus largely on step (2), explaining how the combination of dichotomization and “bias” dilutes experimental evidence, and showing how this dilution leads inevitably to the stated conclusion. We also demonstrate a fallacy in another important component of the argument –that papers in “hot” fields are more likely to produce false findings. We agree with the paper’s conclusions and recommendations that many medical research findings are less definitive than readers suspect, that P-values are widely misinterpreted, that bias of various forms is widespread, that multiple approaches are needed to prevent the literature from being systematically biased and the need for more data on the prevalence of false claims. But calculating the unreliability of the medical research literature, in whole or in part, requires more empirical evidence and different inferential models than were used. The claim that “most research findings are false for most research designs and for most fields” must be considered as yet unproven.

Accuracy of electrocardiography in diagnosis of left ventricular hypertrophy in arterial hypertension: systematic review

OBJECTIVE: To review the accuracy of electrocardiography in screening for left ventricular hypertrophy in patients with hypertension. DESIGN: Systematic review of studies of test accuracy of six electrocardiographic indexes: the Sokolow-Lyon index, Cornell voltage index, Cornell product index, Gubner index, and Romhilt-Estes scores with thresholds for a positive test of > or =4 points or > or =5 points. DATA SOURCES: Electronic databases ((Pre-)Medline, Embase), reference lists of relevant studies and previous reviews, and experts. STUDY SELECTION: Two reviewers scrutinised abstracts and examined potentially eligible studies. Studies comparing the electrocardiographic index with echocardiography in hypertensive patients and reporting sufficient data were included. DATA EXTRACTION: Data on study populations, echocardiographic criteria, and methodological quality of studies were extracted. DATA SYNTHESIS: Negative likelihood ratios, which indicate to what extent the posterior odds of left ventricular hypertrophy is reduced by a negative test, were calculated. RESULTS: 21 studies and data on 5608 patients were analysed. The median prevalence of left ventricular hypertrophy was 33% (interquartile range 23-41%) in primary care settings (10 studies) and 65% (37-81%) in secondary care settings (11 studies). The median negative likelihood ratio was similar across electrocardiographic indexes, ranging from 0.85 (range 0.34-1.03) for the Romhilt-Estes score (with threshold > or =4 points) to 0.91 (0.70-1.01) for the Gubner index. Using the Romhilt-Estes score in primary care, a negative electrocardiogram result would reduce the typical pre-test probability from 33% to 31%. In secondary care the typical pre-test probability of 65% would be reduced to 63%. CONCLUSION: Electrocardiographic criteria should not be used to rule out left ventricular hypertrophy in patients with hypertension.

Prevalence of classical swine fever, Aujeszky's disease and brucellosis in a population of wild boar in Switzerland

During two survey rounds of a national surveillance system for infectious diseases in wild boar in Switzerland, each lasting four months from November to February, between 2001 and 2003, 1949 blood samples and 62 tissue samples from the spleen and 50 from the reproductive organs were collected from hunted wild boar. The survey was designed so that freedom from infection could be detected with a probability of 95 per cent at a threshold prevalence of less than 1 per cent for classical swine fever and Aujeszky's disease and less than 1.5 per cent for brucellosis. There was no serological evidence of classical swine fever or Aujeszky's disease, but brucellosis due to Brucella suis biovar 2 was confirmed serologically and by bacterial isolation.

A genetically explicit model of speciation by sensory drive within a continuous population in aquatic environments

BACKGROUND: The sensory drive hypothesis predicts that divergent sensory adaptation in different habitats may lead to premating isolation upon secondary contact of populations. Speciation by sensory drive has traditionally been treated as a special case of speciation as a byproduct of adaptation to divergent environments in geographically isolated populations. However, if habitats are heterogeneous, local adaptation in the sensory systems may cause the emergence of reproductively isolated species from a single unstructured population. In polychromatic fishes, visual sensitivity might become adapted to local ambient light regimes and the sensitivity might influence female preferences for male nuptial color. In this paper, we investigate the possibility of speciation by sensory drive as a byproduct of divergent visual adaptation within a single initially unstructured population. We use models based on explicit genetic mechanisms for color vision and nuptial coloration. RESULTS: We show that in simulations in which the adaptive evolution of visual pigments and color perception are explicitly modeled, sensory drive can promote speciation along a short selection gradient within a continuous habitat and population. We assumed that color perception evolves to adapt to the modal light environment that individuals experience and that females prefer to mate with males whose nuptial color they are most sensitive to. In our simulations color perception depends on the absorption spectra of an individual's visual pigments. Speciation occurred most frequently when the steepness of the environmental light gradient was intermediate and dispersal distance of offspring was relatively small. In addition, our results predict that mutations that cause large shifts in the wavelength of peak absorption promote speciation, whereas we did not observe speciation when peak absorption evolved by stepwise mutations with small effect. CONCLUSION: The results suggest that speciation can occur where environmental gradients create divergent selection on sensory modalities that are used in mate choice. Evidence for such gradients exists from several animal groups, and from freshwater and marine fishes in particular. The probability of speciation in a continuous population under such conditions may then critically depend on the genetic architecture of perceptual adaptation and female mate choice.

Apparent survival of the salamander

Background Understanding the demographic processes underlying population dynamics is a central theme in ecology. Populations decline if losses from the population (i.e., mortality and emigration) exceed gains (i.e., recruitment and immigration). Amphibians are thought to exhibit little movement even though local populations often fluctuate dramatically and are likely to go exinct if there is no rescue effect through immigration from nearby populations. Terrestrial salamanders are generally portrayed as amphibians with low migratory activity. Our study uses demographic analysis as a key to unravel whether emigration or mortality is the main cause of "losses" from the population. In particular, we use the analysis to challenge the common belief that terrestrial salamanders show low migratory activity. Results The mark-recapture analysis of adult salamanders showed that monthly survival was high (> 90%) without a seasonal pattern. These estimates, however, translate into rather low rates of local annual survival of only ~40% and suggest that emigration was important. The estimated probability of emigration was 49%. Conclusion Our analysis shows that terrestrial salamanders exhibit more migratory activity than commonly thought. This may be due either because the spatial extent of salamander populations is underestimated or because there is a substantial exchange of individuals between populations. Our current results are in line with several other studies that suggest high migratory activity in amphibians. In particular, many amphibian populations may be characterized by high proportions of transients and/or floaters.

Ultrasound-guided paravertebral puncture and placement of catheters in human cadavers: an imaging study

BACKGROUND: During paravertebral block, the anterolateral limit of the paravertebral space, which consists of the pleura, should preferably not be perforated. Also it is possible that, during the block, the constant superior costotransverse ligament can be missed in the loss-of-resistance technique. We therefore aimed to develop a new technique for an ultrasound-guided puncture of the paravertebral space. METHODS: We performed 20 punctures and catheter placements in 10 human cadavers. A sonographic view showing the pleura and the superior costotransverse ligament was obtained with a slightly oblique scan using a curved array transducer. After inline approach, injection of 10 ml normal saline confirmed the correct position of the needle tip, distended the space, and enabled catheter insertion. The spread of contrast dye injected through the catheters was assessed by CT scans. RESULTS: The superior costotransverse ligament and the paravertebral space were easy to identify. The needle tip reached the paravertebral space without problems under visualization. In contrast, the introduction of the catheter was difficult. The CT scan revealed a correct paravertebral spread of contrast in 11 cases. Out of the remaining, one catheter was found in the pleural space, in six cases there was an epidural, and in two cases there was a prevertebral spread of contrast dye. CONCLUSIONS: We successfully developed a technique for an accurate ultrasound-guided puncture of the paravertebral space. We also showed that when a catheter is introduced through the needle with the tip lying in the paravertebral space, there is a high probability of catheter misplacement into the epidural, mediastinal, or pleural spaces.

Hip damage occurs at the zone of femoroacetabular impingement

Although current concepts of anterior femoroacetabular impingement predict damage in the labrum and the cartilage, the actual joint damage has not been verified by computer simulation. We retrospectively compared the intraoperative locations of labral and cartilage damage of 40 hips during surgical dislocation for cam or pincer type femoroacetabular impingement (Group I) with the locations of femoroacetabular impingement in 15 additional hips using computer simulation (Group II). We found no difference between the mean locations of the chondrolabral damage of Group I and the computed impingement zone of Group II. The standard deviation was larger for measures of articular damage from Group I in comparison to the computed values of Group II. The most severe hip damage occurred at the zone of highest probability of femoroacetabular impact, typically in the anterosuperior quadrant of the acetabulum for both cam and pincer type femoroacetabular impingements. However, the extent of joint damage along the acetabular rim was larger intraoperatively than that observed on the images of the 3-D joint simulations. We concluded femoroacetabular impingement mechanism contributes to early osteoarthritis including labral lesions. LEVEL OF EVIDENCE: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Analysis of spring break-up and its effects on a biomass feedstock supply chain in northern Michigan

Demand for bio-fuels is expected to increase, due to rising prices of fossil fuels and concerns over greenhouse gas emissions and energy security. The overall cost of biomass energy generation is primarily related to biomass harvesting activity, transportation, and storage. With a commercial-scale cellulosic ethanol processing facility in Kinross Township of Chippewa County, Michigan about to be built, models including a simulation model and an optimization model have been developed to provide decision support for the facility. Both models track cost, emissions and energy consumption. While the optimization model provides guidance for a long-term strategic plan, the simulation model aims to present detailed output for specified operational scenarios over an annual period. Most importantly, the simulation model considers the uncertainty of spring break-up timing, i.e., seasonal road restrictions. Spring break-up timing is important because it will impact the feasibility of harvesting activity and the time duration of transportation restrictions, which significantly changes the availability of feedstock for the processing facility. This thesis focuses on the statistical model of spring break-up used in the simulation model. Spring break-up timing depends on various factors, including temperature, road conditions and soil type, as well as individual decision making processes at the county level. The spring break-up model, based on the historical spring break-up data from 27 counties over the period of 2002-2010, starts by specifying the probability distribution of a particular county’s spring break-up start day and end day, and then relates the spring break-up timing of the other counties in the harvesting zone to the first county. In order to estimate the dependence relationship between counties, regression analyses, including standard linear regression and reduced major axis regression, are conducted. Using realizations (scenarios) of spring break-up generated by the statistical spring breakup model, the simulation model is able to probabilistically evaluate different harvesting and transportation plans to help the bio-fuel facility select the most effective strategy. For early spring break-up, which usually indicates a longer than average break-up period, more log storage is required, total cost increases, and the probability of plant closure increases. The risk of plant closure may be partially offset through increased use of rail transportation, which is not subject to spring break-up restrictions. However, rail availability and rail yard storage may then become limiting factors in the supply chain. Rail use will impact total cost, energy consumption, system-wide CO2 emissions, and the reliability of providing feedstock to the bio-fuel processing facility.

The influence of concurrent disturbances on plant community dynamics in northern hemlock-hardwood forests

Throughout the Upper Great Lakes region, alterations to historic disturbance regimes have influenced plant community dynamics in hemlock-hardwood forests. Several important mesic forest species, eastern hemlock (Tsuga canadensis), yellow birch (Betula alleghaniensis), eastern white pine (Pinus strobus), and Canada yew (Taxus canadensis), are in decline due to exploitive logging practices used at the turn of the 20th century and the wave of intense fires that followed. Continued regeneration and recruitment failure is attributed to contemporary forest management practices and overbrowsing by white-tailed deer (Odocoileus virginianus). Therefore, I examined the influence of two concurrent disturbances, overstory removal and herbivory, on plant community dynamics in two hemlock-hardwood forests. I measured the post-disturbance regeneration response (herbaceous and woody species) inside and outside of deer exclosures in 20 artificial canopy gaps (50 – 450 m2) and monitored survival and growth for hundreds of planted seedlings. The results of this research show that interacting disturbances can play a large role in shaping plant community composition and structure in hemlock-hardwood forests. White-tailed deer herbivory homogenized the post-disturbance plant communities across the experimental gradient of gap areas, essentially making species compositions in small gaps “look like” those in large gaps. Deer browsing also influenced probability of survival for planted Canada yew cuttings; all else being equal an individual was nearly seven times more likely to survive if protected from herbivory (P < 0.001). In contrast, the ability of sugar maple (Acer saccharum) to persist under high levels of herbivory and respond rapidly to overstory release appears to be related to the presence of stem layering(i.e., portions of below-ground prostrate stem). Layering occurred in 52% of excavated saplings (n = 100) and was significantly associated with increased post-disturbance height growth. Understory light was also important to planted seedling establishment and height growth. Higher levels of direct under-canopy light negatively impacted survival for shade-tolerant hemlock and Canada yew, while an increase in diffuse light was linked to a higher probability of survival for yellow birch and height growth for hemlock and Canada yew. Increases in white pine height growth were also significantly associated with a decrease in canopy cover.

Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries

OBJECTIVE: To analyse the early loss of patients to antiretroviral therapy (ART) programmes in resource-limited settings. METHODS: Using data on 5491 adult patients starting ART (median age 35 years, 46% female) in 15 treatment programmes in Africa, Asia and South America with (3) 12 months of follow-up, we investigated risk factors for no follow-up after treatment initiation, and loss to follow-up or death in the first 6 months. FINDINGS: Overall, 211 patients (3.8%) had no follow-up, 880 (16.0%) were lost to follow-up and 141 (2.6%) were known to have died in the first 6 months. The probability of no follow-up was higher in 2003-2004 than in 2000 or earlier (odds ratio, OR: 5.06; 95% confidence interval, CI: 1.28-20.0), as was loss to follow-up (hazard ratio, HR: 7.62; 95% CI: 4.55-12.8) but not recorded death (HR: 1.02; 95% CI: 0.44-2.36). Compared with a baseline CD4-cell count (3) 50 cells/microl, a count < 25 cells/microl was associated with a higher probability of no follow-up (OR: 2.49; 95% CI: 1.43-4.33), loss to follow-up (HR: 1.48; 95% CI: 1.23-1.77) and death (HR: 3.34; 95% CI: 2.10-5.30). Compared to free treatment, fee-for-service programmes were associated with a higher probability of no follow-up (OR: 3.71; 95% CI: 0.97-16.05) and higher mortality (HR: 4.64; 95% CI: 1.11-19.41). CONCLUSION: Early patient losses were increasingly common when programmes were scaled up and were associated with a fee for service and advanced immunodeficiency at baseline. Measures to maximize ART programme retention are required in resource-poor countries.