Vulvovaginal-swab or first-catch urine specimen to detect Chlamydia trachomatis in women in a community setting?

Screening for chlamydia in women is widely recommended. We evaluated the performance of two nucleic acid amplification tests for detecting Chlamydia trachomatis in self-collected vulvovaginal-swab and first-catch urine specimens from women in a community setting and a strategy for optimizing the sensitivity of an amplified enzyme immunoassay on vulvovaginal-swab specimens. We tested 2,745 paired vulvovaginal-swab and urine specimens by PCR (Roche Cobas) or strand displacement amplification (SDA; Becton Dickinson). There were 146 women infected with chlamydia. The assays detected 97.3% (95% confidence interval [CI], 93.1 to 99.2%) of infected patients with vulvovaginal-swab specimens and 91.8% (86.1 to 95.7%) with urine specimens. We tested 2,749 vulvovaginal-swab specimens with both a nucleic acid amplification test and a polymer conjugate-enhanced enzyme immunoassay with negative-gray-zone testing. The relative sensitivities obtained after retesting specimens in the negative gray zone were 74.3% (95% CI, 62.8 to 83.8%) with PCR and 58.3% (95% CI, 46.1 to 69.8%) with SDA. In community settings, both vulvovaginal-swab and first-catch urine specimens from women are suitable substrates for nucleic acid amplification tests, but enzyme immunoassays, even after negative-gray-zone testing, should not be used in screening programs.     

Chlamydia trachomatis in subfertile women undergoing uterine instrumentation. Screen or treat?

Women who undergo uterine instrumentation are considered at risk for pelvic infections by Chlamydia trachomatis, which may derive either from ascending endocervical infections or from reactivation of micro-organisms persisting in the genital tract after previous chlamydia infections. Women presenting at fertility clinics frequently undergo uterine instrumentation (e.g. hysterosalpingography and laparoscopy with hydrotubation). Studies in subfertile women using DNA amplification techniques have shown that the prevalence of endocervical chlamydia infections is low (1.8%). In contrast, in 30-60% of subfertile women chlamydia IgG antibodies can be found in serum, indicating previous chlamydia infections. It has been demonstrated that, several years after chlamydia infections, viable micro-organisms may still be present in the upper genital tract. Therefore, subfertile women with chlamydia antibodies should be considered at risk for reactivation of persistent chlamydia infections after uterine instrumentation, even after exclusion of endocervical chlamydia infections. Moreover, in subfertile women without chlamydia antibodies, the presence of viable micro-organisms in the genital tract cannot be excluded. As a consequence, prophylactic antibiotics before uterine instrumentation should be considered in all subfertile women, instead of endocervical screening for C. trachomatis and treatment of positive cases only.     

Patient-centered interviewing and student performance in a comprehensive clinical skills examination: Is there an association?

Objective

Communication skills, including patient-centered interviewing (PCI), have become a major priority for educational and licensing organizations in the United States. While patient-centered interviewing is associated with positive patient outcomes and improved diagnostic accuracy, it is unknown if an association exists between patient-centered interviewing and student performance in high-stakes clinical skills assessment (CSA) examinations. The purpose of this study was to determine if generic communication skills and patient-centered interviewing skills were associated with students’ overall student performance on a multi-station clinical skills assessment (CSA) examination.

Methods

This was a cross-sectional study to assess student performance with standardized patients (SPs). We conducted a retrospective review of 30 videotaped SP encounters of Third year medical students (class of 2006) at the University of Kansas School of Medicine. We measured correlations between observed PCI scores, overall CSA scores and CSA interpersonal and communication (ICS) skills scores of student–SP encounters.

Results

PCI scores, as measured with the Four Habits Coding Scheme, a measurement tool of patient-centered communication, were not correlated with either overall CSA scores or ICS scores. Students’ PCI scores were lower than the ICS scores (57% vs. 85% of correct items). The students performed poorly (30% mean score of correct items) in eliciting patient perspectives, compared to three other domains (Invest in the beginning, Demonstrate empathy, and Invest in end) of patient-centered interviewing.

Conclusions

Our study failed to demonstrate any association between student performance and patient-centered interviewing skills (PCI) in the setting of a comprehensive in-house CSA examination. Third-year medical students in our study did not practice some elements of patient-centered interviewing.

Practice implications

Given the increasing importance of patient-centered communication, the high-stakes in-house clinical skills examinations may consider assessing patient-centered interviewing using a more comprehensive and valid checklist.     

22q13 Microduplication in two patients with common clinical manifestations: a recognizable syndrome?

We report here on two unrelated patients (Patients 1 and 2) with a cryptic microduplication involving a 22q13 segment. Both patients manifested infantile hypotonia, developmental delay, and growth deficiency. In addition, an abnormal signal intensity area was detected in the frontal white matter of Patient 2 by brain MRI. Whole-genome microarray comparative genomic hybridization for Patient 1 and fluorescence in situ hybridization analysis with 22q-subtelomeric probes performed in both patients showed a submicroscopic 22q13 duplication that involved the SHANK3 gene. The duplication in Patient 1 was de novo type, while that in Patient 2 was derived from a familial 17;22 translocation. The presence of common clinical manifestations in the two patients with the common duplicated region led to a conclusion that 22q terminal duplication is a recognizable clinical entity, that is, the 22q13 microduplication syndrome.     

Surrogate end-points or primary outcomes in clinical trials in women with polycystic ovary syndrome?

There are multiple surrogate variables in polycystic ovary syndrome (PCOS), including biometric and biochemical parameters. The number of surrogate variables and their poor validity in relationship to primary clinical end-points pose major problems to conducting a trial in women with PCOS. The aim of this review is to discuss the use of surrogate variables compared with primary clinical end-points in women with PCOS. Arguably the best documented correlation between a surrogate variable and a primary clinical end-point is that between ovulation and pregnancy in women with PCOS. Good correlation has been noted between the increase in ovulation frequency with clomiphene citrate and the chance of pregnancy in women with PCOS. However, ovulation cannot be equated with pregnancy, as a host of other factors may affect the true outcome of interest: a healthy liveborn child. Pregnancy and an improvement in hirsutism are clinical end-points that have been successfully studied in past and ongoing clinical trials in women with PCOS. Many other clinical end-points, such as endometrial cancer and cardiovascular disease, are rare in premenopausal women with PCOS, and may not be suitable as the primary outcome of clinical studies. Future multicentre trials in women with PCOS should focus on primary clinical end-points.     

Neuromyotonia with neuropathy and muscle hypertrophy: association or cause?

Continuous muscle fibre activity in a patient with demyelinating neuropathy is rare. We report an 18 year old boy who presented with walking difficulty and continuous rippling in muscles of upper and lower limbs. He had dysarthric speech, hypertrophied arm and calf muscles with normal power, tone, reflexes and sensations. Myokymic discharges were seen in deltoid, biceps, quadriceps and calf muscles. His blood counts, chemistry, thyroid profile, DNA, Rh factor were normal and CPK was raised. CSF showed protein 50 mg/dl and 4 lymphocyte/mm3. Nerve conduction study revealed conduction block and absence of peroneal F wave. EMG showed neuromyotonic discharges which disappeared on regional neuromuscular blocker but not on nerve block or general anaesthesia. He responded partially to prednisolone. Acquired demyelinating neuropathy may result in neuromyotonia and muscle hypertrophy which may partially respond to prednisolone.     

Chlamydia pneumoniae infection and Alzheimer’s disease: a connection to remember?

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, whereby it is customary to distinguish between early familial FAD and late-onset AD (LOAD). The development of LOAD, the most prevalent form of AD, is believed to be a multifactorial process that may also involve infections with bacterial or viral pathogens. After the first report on the presence of Chlamydia pneumoniae (Cpn) in brains of patients with AD appeared in 1998, this bacterium has most often been implicated in AD pathogenesis. However, while some studies demonstrate a clear association between Cpn infection and AD, others have failed to confirm these findings. This might be due to heterogeneity of the specimens analyzed and lack of standardized detection methods. Additionally, non-availability of suitable chlamydial infection models severely hampers research in the field. In this review, we will critically discuss the possible role of Cpn in the pathogenesis of LOAD in light of the available data. We will also present three mutually non-exclusive hypotheses how Cpn might contribute to the pathogenesis of AD.     

Is there an association between inhaled corticosteroids and bone density in postmenopausal women?

BACKGROUND: During the last decades, there has been increased concern about the association between oral corticosteroid (OC) therapy and osteoporosis. OBJECTIVE: The question currently discussed is whether inhaled corticosteroids (ICs) in recommended doses have any clinically relevant effects on bone mineral density (BMD). METHODS: We compared BMD in postmenopausal women exposed to corticosteroids only in inhaled form (IC group, n = 106) with that in women not exposed to corticosteroids (unexposed group, n = 674). BMD was also studied in 49 women exposed to OCs, intra-articular injections, or both in addition to ICs (OC group). The women were recruited from a population-based prospective cohort study. METHODS: We used a dietary survey, bone density measurement of the forearm, and a health questionnaire including an interview about past and present medication use. RESULTS: Mean BMD did not significantly differ between the IC group (0.434 g/cm2) and the unexposed group (0.429 g/cm2). The mean duration and dose of ICs was 8.2 +/- 5.03 years and 853 microg daily. Within the IC group, BMD stratified for cumulative dose of IC, duration, or current dose greater than or less than 1000 microg did not differ. BMD in the OC group was lower than that in the IC group (0.408 vs 0.434 g/cm2). CONCLUSION: No difference in BMD was noted between the IC group and unexposed control subjects, nor was any dose-response relationship observed between IC therapy and BMD.     

Helicobacter infection and cirrhosis in hepatitis C virus carriage: is it an innocent bystander or a troublemaker?

Since it has been shown that Helicobacter hepaticus causes both chronic hepatitis and hepatocellular carcinoma (HCC) in mice, it is suggested that differences in the progression of chronic hepatitis C may be due to a cofactor stemming from co-infection by bacteria, especially Helicobacter pylori, and/or other Helicobacter species. An assessment was made of the prevalence of H. pylori infection in HCV-positive cirrhotic patients. The presence of Helicobacter species (spp). was evaluated in resected liver tissue from HCC patients. Serum anti-H. pylori IgG antibodies were determined in 70 males with a clinical and/or histological diagnosis of cirrhosis and HCV infection and in 310 age-matched male blood donors. The prevalences of H. pylori antibody were 77% (54/70) and 59% (183/310) (P 0.004). Primers identifying 26 Helicobacter species were used to determine the presence of the genomic 16S rRNA of this genus in liver tissue resected from 25 cirrhotic HCC patients. Genomic sequences corresponding to H. pylori and H. pullorum were identified in 23 of these 25 livers. Together, these findings support the proposal that H. pylori is implicated in the pathogenesis and progression of cirrhosis, particularly in HCV-infected individuals. Involvement of Helicobacter spp. in HCC also seems highly possible.     

Asthma prevalence and exacerbations in children: is there an association with childhood vaccination?

Infections and vaccinations may have a potential role in the normal maturation of the immune system, in the development and balance of regulatory pathways, and in the development and exacerbations of asthma. Asthma exacerbations often result from respiratory viral infections, and, while vaccination towards common viral infections may reduce the occurrence of such exacerbations, there has been concern that vaccinations can increase the risk of asthma. Current studies show that childhood vaccines, including inactivated influenza vaccine, are generally safe. However, there is some concern regarding possible exacerbations in infants or children with frequent wheezing or persistent asthma who are given live-attenuated influenza vaccination. Although severe allergic adverse events attributable to vaccination are extremely rare, all serious allergic reactions should be further assessed to detect the likely causative vaccine component, such as egg protein or gelatin. The risks of not vaccinating children far outweigh the risks of allergy and asthma exacerbations. Therefore, childhood vaccination should remain an essential part of child health programs and should not be withheld, even from children with asthma or those predisposed to allergy.     

Genetic risk factors for major depression in men and women: similar or different heritabilities and same or partly distinct genes?

BACKGROUND: Although women are at consistently greater risk for major depression (MD) than men, it is unclear whether sex modifies the aetiological impact of genetic factors on MD. Is the heritability of MD different in men and women? Do the same genetic risk factors predispose to MD in the two sexes? METHODS: We obtained a lifetime history of MD by personal interview on two occasions from 6672 individual twins and 2974 complete twin pairs. Three diagnostic criteria of increasing narrowness were employed: DSM-III-R, DSM-III-R plus impairment and Washington University. To increase power by controlling for unreliability of assessment, we evaluated sex differences on genetic risk for MD using a structural equation measurement model. RESULTS: Using DSM-III-R criteria, but not the two narrower definitions, heritability of MD was significantly greater in women than in men. In the three diagnostic systems, the genetic correlation in liability to MD in men and women was estimated at between +0.50 and +0.65. These estimates differed significantly from unity for the two broader definitions. CONCLUSION: Using broad but not narrower definitions of illness, genetic factors play a greater role in the aetiology of MD in women than in men. The genes that influence risk for MD in the two sexes are correlated but are probably not entirely the same. These results raise the possibility that, in linkage and association studies, the impact of some loci on risk for MD will differ in men and women.     

Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?

We describe a large inbred Syrian pedigree with an autosomal recessive neurodegenerative disorder. The clinical picture of the affected patients is oligodontia, and a degenerative neurological condition with onset around age 12, characterized by progressive ataxia and pyramidal syndrome. Abnormalities in the white matter and cortical atrophy were assessed by magnetic resonance imaging. Differential diagnosis and the possibility of a fortuitous association or the report of a hitherto unreported dento-leukoencephalopathy are discussed.     

Oculocerebrocutaneous and encephalocraniocutaneous lipomatosis syndromes: blind men and an elephant or separate syndromes?

The discovery of relevant causative genes has subdued the lumping versus splitting debate with respect to a growing number of syndromes. However, it remains paramount to define unknown genesis syndromes as precisely and appropriately as possible in order to provide accurate prognosis and to facilitate future research. The presentation of a 14-month-old girl, of normal intelligence, who had a colobomatous right eye with cyst, minor intracranial MRI variants, and an area of sparse scalp hair containing a 1 by 1.5 cm, soft, domed, and indented skin lesion suggested a diagnosis of mild oculocerebrocutaneous syndrome (OCCS). An initial exploration of the literature exposed the extreme variability in cases that have been reported as OCCS, and emphasized its possible relationship to encephalocraniocutaneous lipomatosis (ECCL), thus challenging the initial diagnosis. Cases reported, or discussed by others, as possible OCCS (40) and ECCL (44) were reviewed as completely as possible in an effort to determine whether diagnostic criteria could be developed for these syndromes, and to see whether or not evidence favored their continued separation as two syndromes. The approach used was to summarize the data for all cases, to select major and minor diagnostic criteria on the basis of the relative specificity and/or frequency of a sign, to then apply the criteria in a standard fashion and to review the outcome to see if the classification of cases made clinical sense, and to make appropriate adjustments. The criteria were not chosen so as to separate the syndromes and in some instances the same criteria could apply to either syndrome. An approach is outlined for handling reports of patients that purport to be variants or to expand the spectrum of a syndrome, and in the case of OCCS and ECCL this resulted in most such examples being excluded. Application of diagnostic criteria suggests that OCCS and ECCL are distinct, and that some case reports, including some purporting to expand the spectrum of OCCS, should be excluded, at least until such time as the etiology of these conditions is known and those cases can be tested. These diagnostic criteria were developed on the basis of literature reports that varied in their quantity and quality of detail. Furthermore, in many cases reliance had to be placed on copies of original studies with resultant degradation of photographic information. Modern ocular imaging, and histopathology of eye and skin malformations, will often clarify the specific nature of a malformation and, therefore, define exact diagnostic criteria and leave fewer uncertain cases. In the absence of anomalies in those systems, or if histopathology or appropriate imaging is unavailable, the diagnosis in some cases will continue to remain uncertain; this is not an argument for lumping the syndromes.     

Detection of Chlamydia trachomatis antigen in spontaneous abortions. Is this organism a primary or secondary indicator of risk?

In order to investigate whether or not Chlamydia trachomatis infection is a risk factor for pregnancy loss, 77 spontaneous abortion patients (6-24 weeks gestation), admitted to gynaecology emergency of Safdarjang Hospital, New Delhi, India. Twenty-five pregnant women (6-16 weeks gestation) attending the same hospital for induced abortion, were included in the study. C. trachomatis antigen was detected in endometrial curretage tissue by enzyme immunoassay (EIA). The detection rate was 15.6% (12/77) among spontaneous abortion patients and 4% (1/25) among women undergoing induced abortion. There was no statistically significant association between the mean age/mean gestational age of those experiencing spontaneous abortion, with and without C. trachomatis infection (26.9 years versus 25.06 years and 11.1 weeks versus 9.6 weeks, respectively). High prevalence of C. trachomatis was found in multigravidae and parous spontaneous abortion patients, compared with that in primigravidae and nulliparous Chlamydia-negative spontaneous aborters (75.0% versus 25.0%; 66.7% versus 33.3%, respectively). The prevalence of chlamydial antigen in patients with no prior history of spontaneous abortion was 16.1% (10/62) compared with 18.1% (2/11) in women with one prior abortion. Further study is required to determine whether C. trachomatis infection is a primary or secondary indicator of risk.     

Patient experiences with a phone-based cardiovascular risk reduction intervention: Are there differences between women and men?

ObjectivesTo explore gender-based differences in experiences with a telehealth-delivered intervention for reduction of cardiovascular risk.MethodsWe conducted 23 semi-structured qualitative interviews by telephone with 11 women and 12 men who received a 12-month, pharmacist-delivered, telephone-based medication and behavioral management intervention. We used content analysis to identify themes.ResultsWe identified three common themes for both men and women: ease and convenience of phone support, preference for proactive outreach, and need for trust building in the context of telehealth. While both genders appreciated the social support from the intervention pharmacist, women voiced appreciation for accountability whereas men generally spoke about encouragement.ConclusionsRapport building may differ between telehealth and in-person healthcare visits; our work highlights how men and women’s experiences can differ with telehealth care and which can inform the development of future, purposeful rapport building activities to strengthen the clinician-patient interaction.Practice implicationsClinicians should seek opportunities to provide frequent and routine support for patients with chronic disease. Telehealth interventions may benefit from gender-specific tailoring of social support.     

Salivary testosterone concentrations in left-handers: an association with cerebral language lateralization?

The level of testosterone exposure in early brain development may influence the direction or degree of cerebral language lateralization. Possible links between individual differences in testosterone levels and patterns of speech representation were investigated in 180 healthy young adults (97 left handed, 83 right handed) using the Fused Dichotic Words Test (T. Halwes, 1991). Among left-handed participants, significantly higher testosterone concentrations were observed in individuals with a left-ear advantage on dichotic listening than in individuals with a right-ear advantage. Among right-handed participants, the pattern of group differences in testosterone tended to be reversed, resulting in a statistically significant interaction. Results extend prior findings by S. D. Moffat and E. Hampson (1996a) and raise the possibility that higher testosterone is associated with patterns of brain organization in which speech and praxic functions are lateralized to the same hemisphere.     

Lung cancer and urban air-pollution in Dublin: a temporal association?

In 1990, the sale, marketing and distribution of bituminous coal, primarily used for domestic heating, were banned across Dublin. This study exploits the potential of a 'natural experiment' to assess a temporal association between adjusted annual lung cancer death rates and the changing annual mean urban air-pollution concentrations in Dublin from 1981 to 2000. Annual mean 'black smoke' (BS) concentration was used as an indicator variable for the urban air-pollution mixture. Log-linear Poisson regression model (with an offset) was used to estimate adjusted rate ratios of lung cancer death rates between two periods (1981-1990 and 1991-2000) relative to the year 1990. A significant (p<0.0001) two-third decline in BS concentration (28.2 microg/m(3)) was seen between the two periods [pre-ban (46.4 microg/m(3)) vs. post-ban (18.2 microg/m(3))]. Relative to 1990 (rate ratio= 1 ), a slightly greater decline (2%) in death rates was achieved in the pre-ban period (1981-1990) when mean annual BS concentrations were very high, but a lower decline (1%) was seen in the post-ban period (1991-2000) corresponding to very low mean annual BS concentrations. In other words, a further fall in adjusted rates in lung cancer was achievable both in the pre-ban and the post-ban periods when simultaneously controlling for BS and smoking. A temporal association thus observed between lung cancer death rates and the changing BS concentrations suggests that control of particulate air-pollution could further reduce lung cancer rates, irrespective of smoking patterns.     

Lesions resembling Langerhans cell histiocytosis in association with other lymphoproliferative disorders: a reactive or neoplastic phenomenon?

Langerhans cell histiocytosis (LCH) has been described in association with a variety of neoplasms preceding, after, or synchronous with the other tumor. In some cases, a neoplasm may arise as a complication of therapy for LCH, and in others, the association may be coincidental. Synchronous occurrence has been reported most commonly in association with malignant lymphoma in which discrete proliferations of Langerhans cells (LCs) histologically indistinguishable from LCH are seen. In most cases, these LCs are closely related to or intermingling with the primary pathology. The nature of LCs in this context remains elusive with debate as to whether they represent a true clonal neoplasm or an exaggerated reactive phenomenon. The lack of evidence for LCH progression or disease elsewhere strongly supports the latter. We have encountered 5 examples of LCH-like proliferations occurring in the context of other lymphoproliferative disorders. These include 2 cases of mycosis fungoides and 1 of cutaneous B-cell pseudolymphoma, associations that to our knowledge have not been described before. Two patients were female, and the clonality of the LC proliferation was assessed using laser capture microdissection and the human androgen receptor. The results showed that the LCs forming discrete nodules in a case of cutaneous B-cell pseudolymphoma and a case of Hodgkin's lymphoma were polyclonal. This suggests that, at least in a proportion of cases, the aggregates of LCs occasionally identified within other lymphoproliferative lesions represent a reactive proliferation rather than a potentially aggressive second neoplasm.