Fasting plasma glucose, diagnosis of gestational diabetes and the risk of large for gestational age: a regression discontinuity analysis of routine data.

OBJECTIVE: To estimate the causal effects of fasting plasma glucose (FPG) and diagnosis of gestational diabetes (GDM) on birthweight and the risks of large for gestational age (LGA). DESIGN: Regression discontinuity analysis of routine data. SETTING: Two district general hospitals in West Yorkshire, UK. POPULATION: A cohort of 7062 women with singleton pregnancies who were screened for GDM and gave birth to a baby at ≥24 weeks of gestation in 2017-2019, inclusive. METHODS: The causal effects of FPG and GDM diagnosis were estimated using the two-stage least-squares approach, around the diagnostic threshold of FPG ≥ 5.6 mmol/l recommended by the UK's National Institute for Health and Care Excellent (NICE), controlling for ethnicity, maternal age, parity, height and weight. MAIN OUTCOME MEASURES: Birthweight (standardised for sex and gestational age) and large for gestational age (standardised as birthweight above the 90th centile). RESULTS: For each 1 mmol/l increase in FPG the observed birthweight increased by Z-score = 0.48 standard deviations (95% CI 0.39 to 0.57) and the odds of LGA increased by OR = 2.61 (95% CI 1.86 to 3.66). Conversely, GDM diagnosis reduced the observed birthweight by Z = -0.61 (95% CI -0.94 to -0.29) and lowered the odds of LGA by OR = 0.33 (95% CI 0.15 to 0.74). Similar, but less certain, patterns were observed for caesarean section, shoulder dystocia and perinatal death. CONCLUSIONS: The relationship between FPG and LGA is potent but is dramatically reduced by GDM diagnosis (and all the consequences thereof). Women with mild hyperglycaemia (with an FPG of 5.1-5.5 mmol/l) who fall below the current NICE threshold for GDM diagnosis have the highest risks of adverse outcomes, suggesting a need to reconsider their current care. TWEETABLE ABSTRACT: Regression discontinuity analysis shows that untreated mild hyperglycaemia increases the odds of large for gestational age, but that a diagnosis of gestational #diabetes lowers the odds by three times.

Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected persons.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection for immunocompromised individuals. Robust data and clear guidelines are available for prophylaxis and treatment of human immunodeficiency virus (HIV)-related PCP (HIV-PCP), yet few data and no guidelines are available for non-HIV-related PCP (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP. METHODS: We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP. RESULTS: Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, P = 0.01) and received appropriate antibiotics later in the course of hospitalization (5.2 days vs. 1.1 days, P < 0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1066 days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, P = 0.39) and 90-day mortality (41% vs. 28%, P = 0.20) were detected. CONCLUSIONS: Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis, and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empirical therapy for PCP.

Cord coiling, umbilical cord insertion and placental shape in an unselected cohort delivering at term: relationship with common obstetric outcomes.

BACKGROUND: The position of the placental cord insertion, its shape and cord coiling are thought to be associated with perinatal outcome. This study derives indices describing the relationship of cord insertion to the placental centre, the shape of the placenta and cord coiling in placentas from unselected term pregnancies. Further, we investigate these indices in pregnancies affected by pre-eclampsia (PET), pregnancy induced hypertension (PIH), gestational diabetes mellitus (GDM) and delivery of a small for gestational age (SGA) baby. DESIGN/METHODOLOGY: Eight hundred and sixty one unselected women with singleton pregnancy delivering at 37-42 weeks were prospectively recruited to this study. Placental axes and their relationship with the cord insertion were measured using digital photography and proprietary software. From these, the cord centrality (distance of umbilical cord insertion from the centre) and placental eccentricity (deviation of the placental shape from circular) were derived. The cord coiling index (number of coils in the cord divided by the length of cord in cm) was also calculated from manual measurements. RESULTS: The mean value of cord centrality index was 0.36 (SD = 0.21) and of placental eccentricity 0.49 (SD = 0.17). Left direction of umbilical cord coiling was more common than right (79% vs 16.4%) The mean cord coiling index was 0.20 (SD = 0.09) coils/cm. The indices were constant between 37 and 42 weeks and were no different in the non-affected population compared to women with pre-eclampsia (n = 17), PIH, (n = 27), GDM (n = 38) or delivery of an SGA baby (n = 54). CONCLUSION: The cord centrality index that we derive suggests that the cord insertion is most commonly 'off centre', and eccentricity index that the placental shape is elliptical. Therefore, contrary to widely held belief, the cord does not normally insert centrally nor is the placenta normally round in shape. There is a preponderance of left sided coiling. There was no difference for any of the indices between the non-affected pregnancies and pregnancies affected by pre-eclampsia, PIH, GDM and SGA.

Risk behaviours in HIV-positive men who have sex with men participating in an intervention in a primary care setting.

Men who have sex with men receiving HIV care reported their sexual behaviours and their intentions, classified according to the Transtheoretical Model of Change, to modify the following behaviours: (1) condom use by partner type and activity type; (2) reduction of partner number; and (3) disclosure of HIV serostatus to partners. Most participants were white (68.8%) or black (29.5%) and were more likely to report unprotected sex with HIV-positive than with serodiscordant partners for most activities. Whites reported more partners than black patients (mean 4.1 versus 2; P < 0.0001) and black participants reported fewer HIV-negative (P = 0.0084) and -unknown status partners (P = 0.00095) than whites. Cocaine/crack use was associated with more sexual partners (P = 0.001) and more frequent unprotected sex with HIV-negative or -unknown status partners (P = 0.036). Readiness to change risk behaviour varied by partner status and type of sexual activity. Understanding patients' risks and their readiness to change behaviours may help providers to promote sexual health.

High-risk behaviours among juvenile prison inmates in Pakistan.

OBJECTIVES: To assess the sexual- and drug-use-related risk behaviours of male juvenile detainees in Karachi, Pakistan. DESIGN: Cross-sectional study. METHODS: A cross-sectional study was conducted of prison inmates aged 15-21 years in Karachi Juvenile Prison in 2002. In total, 321 inmates were interviewed about sexual orientation and behaviours, and knowledge about human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). Urine specimens were collected and tested for Chlamydia trachomatis and Neisseria gonorrhoeae using ligase chain reaction. RESULTS: A substantial proportion (n=111, 34.6%) of the participants were sexually active. Sixty-two (19%) and 67 (21%) had had sex with a male or female before incarceration, respectively. Twenty-seven (8.4%) participants had an STI, and 50% of the 109 sexually active participants had had multiple sexual partners. Use of addictive substances was associated with sexual activity. The mean knowledge score computed from the sum of 16 items was 4.7, with a median of 2.9. A large proportion (40%) of participants knew about condoms, but very few (3.4%) had ever used one. The mean+/-standard deviation risk score from nine items was 2.4+/-1.7. On the basis of behavioural and biological markers, 117 (36.4%) participants had high-risk behaviour. In multivariate logistic regression analysis, knowledge, risk perception and age were predictive of higher risk. CONCLUSIONS: HIV risk behaviours are common among adolescent inmates. Although inmates do have knowledge about modes of transmission and condom use, the use of condoms is significantly low. Interventions are needed for behavioural change among this group.

Characteristics of the m2000 automated sample preparation and multiplex real-time PCR system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae.

We evaluated a new real-time PCR-based prototype assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae developed by Abbott Molecular Inc. This assay is designed to be performed on an Abbott m2000 real-time instrument system, which consists of an m2000sp instrument for sample preparation and an m2000rt instrument for real-time PCR amplification and detection. The limit of detection of this prototype assay was determined to be 20 copies of target DNA for both C. trachomatis and N. gonorrhoeae, using serially diluted linearized plasmids. No cross-reactivity could be detected when 55 nongonococcal Neisseria isolates and 3 non-C. trachomatis Chlamydia isolates were tested at 1 million genome equivalents per reaction. Concordance with the Roche Amplicor, BDProbeTec ET, and Gen-Probe APTIMA Combo 2 tests was assessed using unlinked/deidentified surplus clinical specimens previously analyzed with these tests. For C. trachomatis, concordance for positive results ranged from 93.7% to 100%, while concordance for negative results ranged from 98.2% to 100%. For N. gonorrhoeae, concordance for positive and negative results ranged from 91.4% to 100% and 99.3% to 100%, respectively. A workflow analysis of the prototype assay was conducted to obtain information on throughput under laboratory conditions. At 48 samples/run, the time to first result for both C. trachomatis and N. gonorrhoeae was 4.5 h. A total of 135 patient specimens could be analyzed in 8.9 h, with 75 min of hands-on time. This study demonstrated the technical and clinical feasibility of the new Abbott real-time PCR C. trachomatis/N. gonorrhoeae assay.

A multi-centre evaluation of nine rapid, point-of-care syphilis tests using archived sera.

OBJECTIVES: To evaluate nine rapid syphilis tests at eight geographically diverse laboratory sites for their performance and operational characteristics. METHODS: Tests were compared "head to head" using locally assembled panels of 100 archived (50 positive and 50 negative) sera at each site using as reference standards the Treponema pallidum haemagglutination or the T pallidum particle agglutination test. In addition inter-site variation, result stability, test reproducibility and test operational characteristics were assessed. RESULTS: All nine tests gave good performance relative to the reference standard with sensitivities ranging from 84.5-97.7% and specificities from 84.5-98%. Result stability was variable if result reading was delayed past the recommended period. All the tests were found to be easy to use, especially the lateral flow tests. CONCLUSIONS: All the tests evaluated have acceptable performance characteristics and could make an impact on the control of syphilis. Tests that can use whole blood and do not require refrigeration were selected for further evaluation in field settings.

Historical correlates of genital herpes simplex virus type 2 infection in men attending an STD clinic.

BACKGROUND/OBJECTIVES: While nearly one in four Americans has antibodies to HSV-2, only one of 40 reports a history of genital herpes (GH). The goal of this study was to correlate questions designed to elicit a GH history with serological evidence of HSV-2 in male STD clinic attendees. METHODS: Consecutive males were enrolled in a study of the epidemiology of GH. Consenting men answered questionnaires regarding their histories of possible GH and underwent serological testing for HSV-1 and HSV-2. Association statistics between response to each question and HSV-2 serological status were calculated. RESULTS: Of 328 men enrolled, 148 (46%) had HSV-2 antibodies. 14 (4.3%) reported a history of GH when queried as part of a list of other STD (sensitivity (S) 0.08). 17 (5.2%) reported a history of GH when asked directly "Do you have genital herpes?" (S 0.09). 75 (21.1%) participants reported a history of a recurring genital sore, ulcer, or zipper cut (S 0.32). Overall, 64.2% of HSV-2 seropositive men answered "no" to all three questions. A "yes" response to any of the questions was only 36% sensitive for predicting HSV-2 infection. CONCLUSION: Few HSV-2 infected men report either a history of GH or are aware that they are infected. Asking about a history of recurrent genital sores was a more sensitive historical marker of HSV-2 infection than asking about a history of "genital herpes."

Confirming positive results of nucleic acid amplification tests (NAATs) for Chlamydia trachomatis: all NAATs are not created equal.

The Centers for Disease Control and Prevention recommended confirming positive screening tests for Chlamydia trachomatis when positive predictive values are <90%. It is accepted that less sensitive tests (i.e., culture and immunoassays) should not be used to confirm the results of more sensitive nucleic acid amplification tests (NAATs). We show that the same principle applies when NAATs are used for confirmation.

Ability of new APTIMA CT and APTIMA GC assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae in male urine and urethral swabs.

A clinical evaluation was conducted in six North American centers to determine the ability of APTIMA CT (ACT) and APTIMA GC (AGC) nucleic acid amplification assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections in 1,322 men by testing their urethral swabs and first-catch urine (FCU). The results obtained with ACT and AGC assays were compared to an infected patient status determined by testing the specimens with the APTIMA Combo 2 and the BD ProbeTec energy transfer multiplex assays. Symptoms did not influence the values. Positive and negative agreements of the ACT and AGC assays for individual specimens were high, with each comparator assay ranging between 94.3 and 100% for positives and 93.9 and 99.4% for negatives. The ACT and AGC assays performed on noninvasive specimens such as FCU effectively identified C. trachomatis or N. gonorrhoeae infections in symptomatic and asymptomatic men and should be suitable for screening male populations.

Marginal validity of syndromic management for reproductive tract infections among pregnant women in Jamaica.

We assessed the validity of a syndromic case management approach for reproductive tract infections (RTIs) among 371 pregnant women attending antenatal care facilities in Kingston, Jamaica, using an algorithm previously validated in high-risk Jamaican women. For our antenatal attenders, the algorithm had low sensitivities for all RTIs (66.7% for cervicitis, 35.4% for trichomoniasis, 11.1% for bacterial vaginosis (BV) and 24% for candidiasis). Specificities for BV (88.9%) and candidiasis (81.1%) were higher than for cervicitis (62.8%) and trichomoniasis (68.5%). The positive predictive values were lower than 36% for all diagnoses, especially BV (6.9%). Syndromic management of RTIs in pregnant women was problematic using a clinical algorithm that had worked well for high-risk women. Syndromic management for RTIs in Jamaican antenatal clinics is only a temporary solution until more simple and affordable diagnostic tests for RTIs are developed and/or until laboratory support and clinical care can be upgraded at antenatal clinics.

Estimating the costs and benefits of screening monogamous, heterosexual couples for unrecognised infection with herpes simplex virus type 2.

OBJECTIVES: Herpes simplex virus type 2 (HSV-2) is the most common cause of ulcerative genital disease in the United States, but infection is commonly unrecognised. Serological screening tests could identify discordantly infected couples and permit targeted interventions to limit HSV-2 transmission. Our objective was to evaluate the projected cost effectiveness of strategies to prevent HSV-2 transmission in couples with no history of HSV-2 infection. METHODS: We created a mathematical model to simulate the natural history and costs of HSV-2 transmission, and the expected impact of HSV-2 prevention strategies in monogamous, heterosexual couples. Strategies evaluated included (i) no screening; (ii) universal condom use; and (iii) serological screening for HSV-2 with condom use targeted to discordant couples. Screening tests considered included western blot (WB), ELISA, and ELISA with confirmation of positive test results using WB (ELISA-->WB). RESULTS: Compared to no screening, the use of ELISA-->WB prevented 38 future infections per 1000 couples, with a cost effectiveness ratio of $8200 per infection averted. The use of WB in all couples had an incremental cost effectiveness ratio of $63 600 per infection averted. Strategies of ELISA alone and universal condom use were not cost effective. The cost effectiveness of ELISA-->WB improved with increasing prevalence of HSV-2, but worsened with decreasing condom compliance. Screening with ELISA alone was a reasonable strategy only when ELISA specificity increased to 99%. CONCLUSIONS: Serological screening for unrecognised HSV-2 infection in monogamous, heterosexual couples is expected to decrease the incidence of HSV-2 infection, but increase healthcare costs. For couples choosing to be screened, a two step testing strategy (ELISA-->WB) is recommended. Recommendations for a national policy to conduct serological screening will depend on the value placed on averting an incident HSV-2 infection.

Performance of the APTIMA Combo 2 assay for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in female urine and endocervical swab specimens.

The greater sensitivity of nucleic acid amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae permits the use of urine and other noninvasive specimens, which can increase the reach and decrease the costs of public health screening programs aimed at controlling these infections. This study evaluated the performance of the APTIMA Combo 2 assay, a multiplex assay based on the transcription-mediated amplification reaction, for the simultaneous detection of both pathogens in endocervical swab and urine specimens from females. Combo 2 assay results were compared with patient infected status, which were available by using other commercial NAATs. Sensitivity and specificity for C. trachomatis were 94.2 and 97.6%, respectively, in swabs and 94.7 and 98.9%, respectively, in first-catch urine (FCU). Sensitivity and specificity for N. gonorrhoeae were 99.2 and 98.7%, respectively, in swabs and 91.3 and 99.3%, respectively, in FCU. The assay reliably detected both infections in coinfected patients. The Combo 2 assay can be recommended for use with endocervical swab and urine specimens from females, especially for screening tests for asymptomatic women in sexually transmitted disease surveillance programs. This Food and Drug Administration-cleared assay can be a useful tool in efforts to reduce the prevalence and incidence of C. trachomatis and N. gonorrhoeae infections in sexually active women and to prevent their costly and serious sequelae.

Predictors of infection with Trichomonas vaginalis: a prospective study of low income African-American adolescent females.

OBJECTIVES: To identify psychosocial predictors of Trichomonas vaginalis infection among low income African-American adolescent females living in a high risk urban area of the United States. METHODS: Baseline plus 6 and 12 month follow up data collected as part of an HIV prevention intervention trial were utilised. The baseline sample consisted of 522 African-American females, 14-18 years of age. Recruitment sites were located in low income neighbourhoods of Birmingham, Alabama, characterised by high rates of unemployment, substance abuse, violence, teenage pregnancy, and sexually transmitted infections. Self administered vaginal swab specimens were cultured for T vaginalis. Baseline measures collected as part of a self administered survey and face to face interviews were used to predict subsequent infection with T vaginalis at any of the three assessment periods conducted over the span of 1 year. RESULTS: At baseline, 12.9% were diagnosed with T vaginalis. At the 6 and 12 month follow ups, T vaginalis was diagnosed in 8.9% and 10.2%, respectively. The strongest multivariate predictor of T vaginalis infection was biologically confirmed marijuana use; those using marijuana were more than six times as likely to test positive for T vaginalis (adjusted odds ratio (AOR) = 6.2, p = 0.0003). Other multivariate predictors were reporting that typical sex partners were at least 5 years older (AOR = 2.6; p = 0.005), reporting sex with non-steady partners (AOR = 1.9; p = 0.02), and history of delinquency (AOR = 1.3; p = 0.02). The odds of testing positive increased by 31% for every one unit increase on a six item scale measure of delinquency. CONCLUSIONS: Infection with T vaginalis was common and significant multivariate predictors comprised a constellation of problem behaviours, each of which are potentially amenable to behavioural intervention.

Correlates of adolescent females' worry about undesired pregnancy. the importance of partner desire for pregnancy.

STUDY OBJECTIVE: The purpose of this study was to determine correlates of worry about pregnancy among a high-risk sample of low-income African-American adolescent females. Specifically, we tested the hypothesis that perceived male partner desire for pregnancy and level of sexual communication would be independently associated with adolescent females' worry about becoming pregnant. DESIGN: A survey of sexually active African-American adolescent females, 14-18 years of age. SETTING: Recruitment was conducted in low-income neighborhoods of Birmingham, Alabama, characterized by high rates of unemployment, substance abuse, violence, and teen pregnancy. PARTICIPANTS: Adolescents (N = 522) completed a survey and a face-to-face interview, and provided a urine specimen for pregnancy testing. MAIN OUTCOME MEASURE: Nonpregnant adolescents reporting steady relationships with a male sex partner (over the past 6 months) and indicating no immediate desire to become pregnant were included in the analysis (n = 196). Two questionnaire items assessed level of worry about becoming pregnant. RESULTS: Compared to adolescent females reporting their partner did not desire pregnancy, those perceiving their partner desired pregnancy were nearly three times more likely to experience high worry about becoming pregnant (AOR = 2.85; P =.009). Engaging in sex unprotected by a condom was an equally important correlate of high worry (AOR = 2.84; P =.013). Level of communication between partners about pregnancy prevention was not significant. CONCLUSIONS: Adolescent females may experience high worry about becoming pregnant due to desires of their male partner as well as their recent sexual risk behavior.

Enhancement of rural community committee capacity for heart health promotion in Manitoba.

The province of Manitoba is 'rural' by nature, although 70% of its one million people reside within two large urban centres. The Manitoba Heart Health Project (MHHP) province-wide survey (1989) showed that cardiovascular disease (CVD) risk factors were highest and heart health-related knowledge was lowest in the rural population. Working with rural communities, the MHHP Demonstration Project (1992-95) carried out rural heart health promotion using a rural community committee-driven approach with appropriate training, limited resources and at low cost.

Relative accuracy of nucleic acid amplification tests and culture in detecting Chlamydia in asymptomatic men.

Published estimates of the sensitivity and specificity of PCR and ligase chain reaction (LCR) for detecting Chlamydia trachomatis are potentially biased because of study design limitations (confirmation of test results was limited to subjects who were PCR or LCR positive but culture negative). Relative measures of test accuracy are less prone to bias in incomplete study designs. We estimated the relative sensitivity (RSN) and relative false-positive rate (RFP) for PCR and LCR versus cell culture among 1,138 asymptomatic men and evaluated the potential bias of RSN and RFP estimates. PCR and LCR testing in urine were compared to culture of urethral specimens. Discordant results (PCR or LCR positive, but culture negative) were confirmed by using a sequence including the other DNA amplification test, direct fluorescent antibody testing, and a DNA amplification test to detect chlamydial major outer membrane protein. The RSN estimates for PCR and LCR were 1.45 (95% confidence interval [CI] = 1.3 to 1.7) and 1.49 (95% CI = 1.3 to 1.7), respectively, indicating that both methods are more sensitive than culture. Very few false-positive results were found, indicating that the specificity levels of PCR, LCR, and culture are high. The potential bias in RSN and RFP estimates were <5 and <20%, respectively. The estimation of bias is based on the most likely and probably conservative parameter settings. If the sensitivity of culture is between 60 and 65%, then the true sensitivity of PCR and LCR is between 90 and 97%. Our findings indicate that PCR and LCR are significantly more sensitive than culture, while the three tests have similar specificities.

Urethral cytokine and immune responses in Chlamydia trachomatis-infected males.

Penile urethral swabs collected from PCR-confirmed Chlamydia trachomatis-infected, C. trachomatis-uninfected, and non-C. trachomatis-infected, nongonococcal urethritis-infected males were analyzed for cytokine, total immunoglobulin (Ig), and specific antibody levels by enzyme-linked immunosorbent assay. Differential cellular components of the swab transport medium were also enumerated for the same groups. Although low, the levels of C. trachomatis-specific IgA and IgG antibodies and interleukin 8 cytokine were significantly higher in C. trachomatis-infected individuals. There were no significant differences in the levels of seven additional cytokines evaluated.