Screening and treatment to prevent sequelae in women with Chlamydia trachomatis genital infection: how much do we know?

Background. An important question for chlamydia control programs is the extent to which finding and treating prevalent, asymptomatic Chlamydia trachomatis genital infection reduces reproductive sequelae in infected women. Methods. We reviewed the literature to critically evaluate evidence on the effect of chlamydia screening on development of sequelae in infected women. Results. Two randomized controlled trials of 1-time screening for chlamydial infection—in a Seattle-area health maintenance organization and a Danish school district—revealed that screening was associated with an ∼50% reduction in the incidence of pelvic inflammatory disease over the following year. However, both of these trials had methodological issues that may have affected the magnitude of observed screening benefits and might limit generalizability to other populations. A large, nonrandomized cohort of chlamydia screening among US Army recruits, although limited by lack of outpatient data, did not find a benefit of similar magnitude to the randomized trials. Methodological limitations restrict valid conclusions about individual benefits of screening using data from historical cohorts and ecological studies. We identified no trials directly evaluating the effect of chlamydia screening on subclinical tubal inflammation or damage, ectopic pregnancy, or tubal factor infertility and no studies addressing the effects of >1 round of screening, the optimal frequency of screening, or the benefits of screening for repeat infections. Conclusions. Additional studies of the effectiveness of chlamydia screening would be valuable; feasible study designs may depend on the degree to which screening programs are already established. In addition, better natural history data on the timing of tubal inflammation and damage after C. trachomatis infection and development of more accurate, noninvasive tools to assess chlamydial sequelae are essential to informing chlamydia control efforts.

Risk of sequelae after Chlamydia trachomatis genital infection in women

Chlamydia trachomatis infection, the most common reportable disease in the United States, can lead to pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain. Although C. trachomatis is identified among many women who receive a diagnosis of PID, the incidence and timing of PID and long-term sequelae from an untreated chlamydial infection have not been fully determined. This article examines evidence reviewed as part of the Centers for Disease Control and Prevention Chlamydia Immunology and Control Expert Advisory Meeting; 24 reports were included. We found no prospective studies directly assessing risk of long-term reproductive sequelae, such as infertility, after untreated C. trachomatis infection. Several studies assessed PID diagnosis after untreated chlamydial infection, but rates varied widely, making it difficult to determine an overall estimate. In high-risk settings, 2%-5% of untreated women developed PID within the approximately 2-week period between testing positive for C. trachomatis and returning for treatment. However, the rate of PID progression in the general, asymptomatic population followed up for longer periods appeared to be low. According to the largest studies, after symptomatic PID of any cause has occurred, up to 18% of women may develop infertility. In several studies, repeated chlamydial infection was associated with PID and other reproductive sequelae, although it was difficult to determine whether the risk per infection increased with each recurrent episode. The present review critically evaluates this body of literature and suggests future research directions. Specifically, prospective studies assessing rates of symptomatic PID, subclinical tubal damage, and long-term reproductive sequelae after C. trachomatis infection; better tools to measure PID and tubal damage; and studies on the natural history of repeated chlamydial infections are needed.

Long-term sequelae after acquired pediatric hemorrhagic cerebellar lesions

The aim of the present study was to assess cognitive, affective, and motor long-term sequelae after acquired focal pediatric cerebellar lesions.

Injuries, sequelae, and treatment of lightning-induced injuries: 10 years of experience at a swiss trauma center

Principals. Lightning is one of the most powerful and spectacular natural phenomena. Lightning strikes to humans are uncommon but can cause devastating injuries. We analyzed lightning-related admissions to our emergency department from January 2000 to December 2010 to review and highlight the main features of lightning-related injuries. Methods. All data were collected prospectively and entered in the emergency department' database (Qualicare Switzerland) and retrospectively analyzed. Results. Nine patients with lightning-related injuries presented to our emergency department. Four were female, and five were male. The most common site of injury was the nervous system (6 out of 9 patients) followed by the cardiovascular system (5 out of 9 patients). The third most common injuries occurred to the skin (3 out of 9 patients). Four of the patients had to be hospitalized for further observation. Conclusion. Reports of lightning strikes and related injuries are scarce. The establishment of an international register would therefore benefit the understanding of their injury patterns and facilitate specific treatment.

Prospects for microbeam radiation therapy of brain tumours in children to reduce neurological sequelae

Microbeam radiation therapy (MRT), a form of experimental radiosurgery of tumours using multiple parallel, planar, micrometres-wide, synchrotron-generated X-ray beams ('microbeams'), can safely deliver radiation doses to contiguous normal animal tissues that are much higher than the maximum doses tolerated by the same normal tissues of animals or patients from any standard millimetres-wide radiosurgical beam. An array of parallel microbeams, even in doses that cause little damage to radiosensitive developing tissues, for example, the chick chorioallantoic membrane, can inhibit growth or ablate some transplanted malignant tumours in rodents. The cerebella of 100 normal 20 to 38g suckling Sprague-Dawley rat pups and of 13 normal 5 to 12kg weanling Yorkshire piglets were irradiated with an array of parallel, synchrotron-wiggler-generated X-ray microbeams in doses overlapping the MRT-relevant range (about 50-600Gy) using the ID17 wiggler beamline tangential to the 6GeV electron synchrotron ring at the European Synchrotron Radiation Facility in Grenoble, France. Subsequent favourable development of most animals over at least 1 year suggests that MRT might be used to treat children's brain tumours with less risk to the development of the central nervous system than is presently the case when using wider beams.

Mechanical circulatory support as a bridge to heart transplantation: what remains? Long-term emotional sequelae in patients and spouses

Implantation of a ventricular assist device (VAD) reduces short-term mortality and morbidity and provides patients with reasonable quality of life even though it may also be a long-lasting emotional burden. This study was conducted to analyze the long-time emotional consequences of VAD implantation, followed by heart transplantation in patients and spouses.

[Pre-eclampsia and its psychosocial sequelae]

In the present work some psychosomatic conditions in the setting of preeclampsia are described. The important psychosocial consequences for women suffering from this disease and the drawback for their partners will be elucidated. Preeclampsia as a disease including hypertension, proteinuria and generalized edema is often associted with generalized seizures occuring most commonly at the end of the second trimenon of pregnancy. The disease bears a heavy risk for the mothers as well as for her unborn child. Until now the exact pathophysiological basis of the disease has not been entirely elucidated. For the pregnant woman and her psychosocial surrounding the outbreak of the disease is in most cases unexpected. During development of the disease she has to face a role change from a so far normal pregnancy to a high-risk situation. This may change also the attitude to the unborn child by herself and her partner. The preterm delivery induced therapeutically, together with the succeeding problems for the newborn complete the high psychosocial stress related to the entire situation. Therefore it is useful and important to offer psychosocial support to the mother as well as to her parter during the illness and the time after delivery.

Valuing the Health States Associated with Chlamydia trachomatis Infections and Their Sequelae: A Systematic Review of Economic Evaluations and Primary Studies

OBJECTIVES Economic evaluations of interventions to prevent and control sexually transmitted infections such as Chlamydia trachomatis are increasingly required to present their outcomes in terms of quality-adjusted life-years using preference-based measurements of relevant health states. The objectives of this study were to critically evaluate how published cost-effectiveness studies have conceptualized and valued health states associated with chlamydia and to examine the primary evidence available to inform health state utility values (HSUVs). METHODS A systematic review was conducted, with searches of six electronic databases up to December 2012. Data on study characteristics, methods, and main results were extracted by using a standard template. RESULTS Nineteen economic evaluations of relevant interventions were included. Individual studies considered different health states and assigned different values and durations. Eleven studies cited the same source for HSUVs. Only five primary studies valued relevant health states. The methods and viewpoints adopted varied, and different values for health states were generated. CONCLUSIONS Limitations in the information available about HSUVs associated with chlamydia and its complications have implications for the robustness of economic evaluations in this area. None of the primary studies could be used without reservation to inform cost-effectiveness analyses in the United Kingdom. Future debate should consider appropriate methods for valuing health states for infectious diseases, because recommended approaches may not be suitable. Unless we adequately tackle the challenges associated with measuring and valuing health-related quality of life for patients with chlamydia and other infectious diseases, evaluating the cost-effectiveness of interventions in this area will remain problematic.

A systematic approach to analyse the sequelae of LCPD

The analysis and treatment of hips with healed Legg-Calvé-Perthes disease (LCPD) differs substantially from the treatment in the acute phase of the disease. More specifically, the treating orthopaedic surgeon is often faced with a complex three-dimensional pathomorphology of the hip that is difficult to understand and correct. To date, none of the current classification systems provide a useful decision-making algorithm with regards to the type of surgical intervention necessary to improve hip function in patients with sequelae of LCPD. The conceptual recognition of the femoroacetabular impingement (FAI) and the ability to safely dislocate the hip have revolutionised our diagnostic and therapeutic algorithm for joint-preserving surgery of hips with structural residuals of LCPD. We present a systematic approach to analyse femoral and acetabular pathomorphologic features. The resulting pathomechanisms and the surgical treatment options are presented.

Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae.

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF specimens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae.

Neuropsychological long-term sequelae after posterior fossa tumour resection during childhood

The importance of the cerebellum for non‐motor functions is becoming more and more evident. The influence on cognitive functions from acquired cerebellar lesions during childhood, however, is not well known. We present follow‐up data from 24 patients, who were operated upon during childhood for benign cerebellar tumours. The benign histology of these tumours required neither radiotherapy nor chemotherapy. Post‐operatively, these children were of normal intelligence with a mean IQ of 99.1, performance intelligence quotient (PIQ) of 101.3 and verbal intelligence quotient (VIQ) of 96.8. However, 57% of patients showed abnormalities in subtesting. In addition, more extensive neuropsychological testing revealed significant problems for attention, memory, processing speed and interference. Visuo‐constructive problems were marked for copying the Rey figure, but less pronounced for recall of the figure. Verbal fluency was more affected than design fluency. Behavioural deficits could be detected in 33% of patients. Attention deficit problems were marked in 12.5%, whereas others demonstrated psychiatric symptoms such as mutism, addiction problems, anorexia, uncontrolled temper tantrums and phobia. Age at tumour operation and size of tumour had no influence on outcome. Vermis involvement was related to an increase in neuropsychological and psychiatric problems. The observation that patients with left‐sided cerebellar tumours were more affected than patients with right‐sided tumours is probably also influenced by a more pronounced vermian involvement in the former group. In summary, this study confirms the importance of the cerebellum for cognitive development and points to the necessity of careful follow‐up for these children to provide them with the necessary help to achieve full integration into professional life.

Sample size considerations using mathematical models: an example with Chlamydia trachomatis infection and its sequelae pelvic inflammatory disease.

BACKGROUND The success of an intervention to prevent the complications of an infection is influenced by the natural history of the infection. Assumptions about the temporal relationship between infection and the development of sequelae can affect the predicted effect size of an intervention and the sample size calculation. This study investigates how a mathematical model can be used to inform sample size calculations for a randomised controlled trial (RCT) using the example of Chlamydia trachomatis infection and pelvic inflammatory disease (PID). METHODS We used a compartmental model to imitate the structure of a published RCT. We considered three different processes for the timing of PID development, in relation to the initial C. trachomatis infection: immediate, constant throughout, or at the end of the infectious period. For each process we assumed that, of all women infected, the same fraction would develop PID in the absence of an intervention. We examined two sets of assumptions used to calculate the sample size in a published RCT that investigated the effect of chlamydia screening on PID incidence. We also investigated the influence of the natural history parameters of chlamydia on the required sample size. RESULTS The assumed event rates and effect sizes used for the sample size calculation implicitly determined the temporal relationship between chlamydia infection and PID in the model. Even small changes in the assumed PID incidence and relative risk (RR) led to considerable differences in the hypothesised mechanism of PID development. The RR and the sample size needed per group also depend on the natural history parameters of chlamydia. CONCLUSIONS Mathematical modelling helps to understand the temporal relationship between an infection and its sequelae and can show how uncertainties about natural history parameters affect sample size calculations when planning a RCT.

Twelve percent of hips with a primary cam deformity exhibit a slip-like morphology resembling sequelae of slipped capital femoral epiphysis

BACKGROUND In some hips with cam-type femoroacetabular impingement (FAI), we observed a morphology resembling a more subtle form of slipped capital femoral epiphysis (SCFE). Theoretically, the morphology in these hips should differ from hips with a primary cam-type deformity. QUESTIONS/PURPOSES We asked if (1) head-neck offset; (2) epiphyseal angle; and (3) tilt angle differ among hips with a slip-like morphology, idiopathic cam, hips after in situ pinning of SCFE, and normal hips; and (4) what is the prevalence of a slip-like morphology among cam-type hips? METHODS We retrospectively compared the three-dimensional anatomy of hips with a slip-like morphology (29 hips), in situ pinning for SCFE (eight hips), idiopathic cam deformity (171 hips), and 30 normal hips using radial MRI arthrography. Normal hips were derived from 17 asymptomatic volunteers. All other hips were recruited from a series of 277 hips (243 patients) seen at a specialized academic hip center between 2006 and 2010. Forty-one hips with isolated pincer deformity were excluded. Thirty-six of 236 hips had a known cause of cam impingement (secondary cam), including eight hips after in situ pinning of SCFE (postslip group). The 200 hips with a primary cam were separated in hips with a slip-like morphology (combination of positive fovea sign [if the neck axis did not intersect with the fovea capitis] and a tilt angle [between the neck axis and perpendicular to the basis of the epiphysis] exceeding 4°) and hips with an idiopathic cam. We evaluated offset ratio, epiphyseal angle (angle between the neck axis and line connecting the center of the femoral head and the point where the physis meets the articular surface), and tilt angle circumferentially around the femoral head-neck axis. Prevalence of slip-like morphology was determined based on the total of 236 hips with cam deformities. RESULTS Offset ratio was decreased anterosuperiorly in idiopathic cam, slip-like, and postslip (eg, 1 o'clock position with a mean offset ranging from 0.00 to 0.14; p < 0.001 for all groups) compared with normal hips (0.25 ± 0.06 [95% confidence interval, 0.13-0.37]) and increased posteroinferiorly in slip-like (eg, 8 o'clock position, 0.5 ± 0.09 [0.32-0.68]; p < 0.001) and postslip groups (0.55 ± 0.12 [0.32-0.78]; p < 0.001) and did not differ in idiopathic cam (0.32 ± 0.09 [0.15-0.49]; p = 0.323) compared with normal (0.31 ± 0.07 [0.18-0.44]) groups. Epiphyseal angle was increased anterosuperiorly in the slip-like (eg, 1 o'clock position, 70° ± 9° [51°-88°]; p < 0.001) and postslip groups (75° ± 13° [49°-100°]; p = 0.008) and decreased in idiopathic cam (50° ± 8° [35°-65°]; p < 0.001) compared with normal hips (58° ± 8° [43°-74°]). Posteroinferiorly, epiphyseal angle was decreased in slip-like (eg, 8 o'clock position, 54° ± 10° [34°-74°]; p < 0.001) and postslip (44° ± 11° [23°-65°]; p < 0.001) groups and did not differ in idiopathic cam (76° ± 8° [61°-91°]; p = 0.099) compared with normal (73° ± 7° [59°-88°]) groups. Tilt angle increased in slip-like (eg, 2/8 o'clock position, 14° ± 8° [-1° to 30°]; p < 0.001) and postslip hips (29° ± 10° [9°-48°]; p < 0.001) and decreased in hips with idiopathic cam (-7° ± 5° [-17° to 4°]; p < 0.001) compared with normal (-1° ± 5° [-10° to 8°]) hips. The prevalence of a slip-like morphology was 12%. CONCLUSIONS The slip-like morphology is the second most frequent pathomorphology in hips with primary cam deformity. MRI arthrography of the hip allows identifying a slip-like morphology, which resembles hips after in situ pinning of SCFE and distinctly differs from hips with idiopathic cam. These results support previous studies reporting that SCFE might be a risk factor for cam-type FAI.