Clostridium perfringens Septicemia and a Bleeding Ulcer of a Jejunal Interposition: A Case Report and Short Review of the Literature.

INTRODUCTION: We report a case of Clostridium perfringens septicemia in a patient presenting with a bleeding ulcer of a jejunal interposition. CASE PRESENTATION: An 81-year-old female patient was acutely admitted to our hospital due to hematemesis and melena. She had a history of metastatic gastrointestinal stromal tumor, for which she was receiving second line treatment with sunitinib. She had also undergone a Merendino procedure 4 years prior to presentation. The patient underwent emergency gastroscopy, which revealed a bleeding ulcer in the jejunal interposition. Despite initial endoscopic control of the bleeding and transfusion of blood products, the hemoglobin level continued to drop, and the patient was treated for an assumed hemolytic transfusion reaction. The patient died 3 days following admission, and the results of blood cultures later confirmed a Clostridium perfringens septicemia. The postmortem examination revealed a diffuse spread of Clostridium perfringens to multiple organs. CONCLUSION: This case is a reminder of the importance of considering septicemia, particularly in association with Clostridium perfringens, as a potential cause of hemolysis. It also demonstrates the extent of organ involvement in a case of diffuse clostridial myonecrosis.

Perceived effects of innovations in postgraduate medical education: a Q study focusing on workplace-based assessment.

PURPOSE: Anticipating users' perceptions of the effects an innovation will have in daily practice prior to implementation may lead to a more optimal innovation process. In this study, the authors aimed to identify the kinds of perceptions that exist concerning the effects of workplace-based assessment (WBA), an innovation that is widely used in medical education, among its users. METHOD: In 2012, the authors used Q methodology to ascertain the principal user perceptions of effects of WBA in practice. Participating obstetrics-gynecology residents and attending physicians (including residency program directors) at six hospitals in the Netherlands performed individual Q sorts to rank 36 statements concerning WBA and WBA tools according to their level of agreement. The authors conducted by-person factor analysis to uncover patterns in the rankings of the statements. They used the statistical results and participant comments about their sorts to interpret and describe distinct perceptions. RESULTS: The analysis of 65 Q sorts (completed by 22 residents and 43 attendings) identified five distinct user perceptions regarding the effects of WBA in practice, which the authors labeled enthusiasm, compliance, effort, neutrality, and skepticism. These perceptions were characterized by differences in views on three main issues: the intended goals of the innovation, its applicability (ease of applying it to practice), and its actual impact. CONCLUSIONS: User perceptions of the effects of innovations in medical education can be typified and should be anticipated. This study's insights into five principal user perceptions can support the design and implementation of innovations in medical education.

Serovar D and E of serogroup B induce highest serological responses in urogenital Chlamydia trachomatis infections.

BACKGROUND: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) worldwide. A strong link between C. trachomatis serogroup/serovar and serological response has been suggested in a previous preliminary study. The aim of the current study was to confirm and strengthen those findings about serological IgG responses in relation to C. trachomatis serogroups and serovars. METHODS: The study population (n = 718) consisted of two patient groups with similar characteristics of Dutch STI clinic visitors. We performed genotyping of serovars and used titre based and quantitative commercially available ELISA kits (medac Diagnostika) to determine specific serum IgG levels. Optical density (OD) values generated by both tests were used to calculate the IgG titres (cut-off 1:50). Analyses were conducted stratified by gender. RESULTS: We observed very significant differences when comparing the median IgG titres of three serogroups, B, C and I: in women for B vs. C: p < 0.0001 (median titres B 200 vs. C <50); B vs. I: p < 0.0001 (200 vs. 50), and in men for B vs. C: p = 0.0006 (150 vs. <50); B vs. I: p = 0.0001 (150 vs. <50); C vs. I was not significant for both sexes. Serovars D and E of serogroup B had the highest median IgG titres compared to the other serovars in both men and women: 200 and 200 vs. ≤ 100 for women and 100 and 200 vs. ≤ 75 for men, respectively. CONCLUSIONS: This study shows that B group serovars induce higher serological responses compared to the C and I group serovars in vivo in both men and women.

Adhesion awareness: a nationwide survey of gynaecologists.

OBJECTIVE: Adhesions and related complications lead to substantially increased morbidity and mortality which increase medical costs. We investigated the awareness of adhesions among Dutch gynaecologists and gynaecology residents. STUDY DESIGN: A survey, assessing knowledge and opinion about adhesions, was sent to a randomly selected group of 381 gynaecologists and 256 residents. In addition, the informed consent process and application of anti-adhesive agents were questioned. RESULTS: The response rate was 56.9%. Complications due to adhesions were highly underestimated, leading to low knowledge scores (mean score 35.1%). Of all respondents 73.8% agreed that adhesions exert a clinically relevant and negative effect, but only 51.2% expressed a positive opinion on adhesion prevention. This correlated with a stronger belief in the clinically relevant and negative effects of adhesions and the opinion that adhesion prevention belongs to standard care (ρ=0.212, p<0.001; ρ=0.495, p<0.001). Of all respondents 31.4% expressed a positive attitude towards anti-adhesive agents and 19.8% expressed a negative one. A negative attitude correlated with a negative view in terms of cost-benefits (ρ=0.245, p<0.001). Although 43.5% had used anti-adhesive agents in the past year, 20.9% had used them before but stopped using agents in the past year. Only 5.2% routinely included adhesions or related morbidity in the informed consent. CONCLUSIONS: Awareness of adhesions is limited and informed consent is provided inadequately. Implementing adhesion prevention is related with awareness of adhesions. These findings underline the need to embed adhesions, related morbidity and prevention in educational programmes.

Exploration of perceived effects of innovations in postgraduate medical education.

CONTEXT: Many studies have examined how educational innovations in postgraduate medical education (PGME) impact on teaching and learning, but little is known about effects in the clinical workplace outside the strictly education-related domain. Insights into the full scope of effects may facilitate the implementation and acceptance of innovations because expectations can be made more realistic, and difficulties and pitfalls anticipated. Using workplace-based assessment (WBA) as a reference case, this study aimed to determine which types of effect are perceived by users of innovations in PGME. METHODS: Focusing on WBA as a recent instance of innovation in PGME, we conducted semi-structured interviews to explore perceptions of the effects of WBA in a purposive sample of Dutch trainees and (lead) consultants in surgical and non-surgical specialties. Interviews conducted in 2011 with 17 participants were analysed thematically using template analysis. To support the exploration of effects outside the domain of education, the study design was informed by theory on the diffusion of innovations. RESULTS: Six domains of effects of WBA were identified: sentiments (affinity with the innovation and emotions); dealing with the innovation; specialty training; teaching and learning; workload and tasks, and patient care. Users' affinity with WBA partly determined its effects on teaching and learning. Organisational support and the match between the innovation and routine practice were considered important to minimise additional workload and ensure that WBA was used for relevant rather than easily assessable training activities. Dealing with WBA stimulated attention for specialty training and placed specialty training on the agenda of clinical departments. CONCLUSIONS: These outcomes are in line with theoretical notions regarding innovations in general and may be helpful in the implementation of other innovations in PGME. Given the substantial effects of innovations outside the strictly education-related domain, individuals designing and implementing innovations should consider all potential effects, including those identified in this study.

How lead consultants approach educational change in postgraduate medical education.

CONTEXT: Consultants in charge of postgraduate medical education (PGME) in hospital departments ('lead consultants') are responsible for the implementation of educational change. Although difficulties in innovating in medical education are described in the literature, little is known about how lead consultants approach educational change. OBJECTIVES: This study was conducted to explore lead consultants' approaches to educational change in specialty training and factors influencing these approaches. METHODS: From an interpretative constructivist perspective, we conducted a qualitative exploratory study using semi-structured interviews with a purposive sample of 16 lead consultants in the Netherlands between August 2010 and February 2011. The study design was based on the research questions and notions from corporate business and social psychology about the roles of change managers. Interview transcripts were analysed thematically using template analysis. RESULTS: The lead consultants described change processes with different stages, including cause, development of content, and the execution and evaluation of change, and used individual change strategies consisting of elements such as ideas, intentions and behaviour. Communication is necessary to the forming of a strategy and the implementation of change, but the nature of communication is influenced by the strategy in use. Lead consultants differed in their degree of awareness of the strategies they used. Factors influencing approaches to change were: knowledge, ideas and beliefs about change; level of reflection; task interpretation; personal style, and department culture. CONCLUSIONS: Most lead consultants showed limited awareness of their own approaches to change. This can lead them to adopt a rigid approach, whereas the ability to adapt strategies to circumstances is considered important to effective change management. Interventions and research should be aimed at enhancing the awareness of lead consultants of approaches to change in PGME.

Analyses of multiple-site and concurrent Chlamydia trachomatis serovar infections, and serovar tissue tropism for urogenital versus rectal specimens in male and female patients.

OBJECTIVES: The aims of this study were: to determine the incidence of concurrent infections on a serovar level; to determine the incidence of multiple anatomical infected sites on a detection and genotyping level and analyse site-specific serovar distribution; to identify tissue tropism in urogenital versus rectal specimens. METHODS: Chlamydia trachomatis-infected patients in two populations were analysed: 75 visiting the outpatient department of obstetrics and gynaecology of the MC Haaglanden, and 358 visiting the outpatient sexually transmitted disease clinic, The Hague, The Netherlands. The PACE 2 assay (Gen-Probe) was used to detect C trachomatis from urethral, cervical, vaginal, oropharyngeal and anorectal swabs. C trachomatis genotyping was performed on all C trachomatis positive samples, using the CT-DT genotyping assay. RESULTS: Samples from 433 patients (256 female and 177 male) with confirmed C trachomatis infection were analysed. In 11 patients (2.6%), concurrent serovars in one anatomical sample site were present. In 62 (34.1%) female and four (9.3%) male patients, multiple sample site infections were found. A substantial percentage of women tested at the cervical/vaginal and rectal site were found to be positive at both sites (36.1%, 22/61). In men, D/Da and G/Ga serovars were more prevalent in rectal than urogenital specimens (p=0.0081 and p=0.0033, respectively), while serovar E was more prevalent in urogenital specimens (p=0.0012). CONCLUSIONS: The prevalence of multiple serovar infections is relatively low. Significant differences in serovar distribution are found in rectal specimens from men, with serovar G/Ga being the most prominent, suggesting tissue tropism.

Pharmacokinetics of clindamycin in pregnant women in the peripartum period.

The study presented here was performed to determine the pharmacokinetics of intravenously administered clindamycin in pregnant women. Seven pregnant women treated with clindamycin were recruited. Maternal blood and arterial and venous umbilical cord blood samples were obtained. Maternal clindamycin concentrations were analyzed by nonlinear mixed-effects modeling with the NONMEM program. The data were best described by a linear three-compartment model. The clearance and the volume of distribution at steady state were 10.0 liters/h and 6.32 x 10(3) liters, respectively. Monte Carlo simulations were performed to determine the area under the concentration curve (AUC) for the free (unbound) drug (f) in maternal serum for 24 h divided by the MIC (fAUC(0-24)/MIC). At a MIC of 0.5 mg/liter, which is the EUCAST breakpoint, the attainment at the lower 95% confidence interval (CI) was 24.6 if the level of protein binding was 65%, and this value concurred well with the target value of 27. However, for higher degrees of protein binding, as has been described in the literature, the attainment was lower, down to 10.2 for a protein binding level of 85% (lower 95% CI). The concentrations in umbilical cord blood were lower than those in maternal blood. The concentration-time profiles in maternal serum indicate that the level of exposure to clindamycin may be too low in these patients. Together with the lower concentrations in umbilical cord blood, this finding suggests that the current dosing regimen may not be adequate to protect all neonates from group B streptococcal disease.

Timing of group B streptococcus screening in pregnancy: a systematic review.

BACKGROUND: Group B streptococcus (GBS) is an important cause of neonatal sepsis. Guidelines advise to collect cultures at 35-37 weeks' gestation and to administer intrapartum antibiotic prophylaxis in case of GBS-positive cultures, as well as in all preterm deliveries. Improved effectiveness of antenatal cultures might help to further decrease GBS early-onset disease. OBJECTIVE: To determine the best timing of antenatal cultures, which may help establish optimal prevention of perinatal GBS infection in both term and preterm neonates. METHODS: PubMed and EMBASE databases were searched for relevant articles published from 1966 to February 2009. Nine articles were included. Information about study features and predictive values of antenatal cultures were abstracted. RESULTS: Positive predictive values for antenatal GBS cultures ranged from 43 to 100% (mean 69%) and negative predictive values from 80 to 100% (mean 94%). GBS cultures collected in late pregnancy had high positive predictive values for colonization during delivery. The negative predictive value was high and relatively constant regardless of GA. CONCLUSIONS: This systematic review confirms recommendations to screen pregnant women for colonization of GBS at 35-37 weeks' gestation, but one should be aware of the limitations of screening, with 6% of GBS carriers remaining undetected in antenatal cultures.

Significantly higher serologic responses of Chlamydia trachomatis B group serovars versus C and I serogroups.

Chlamydia trachomatis serovars are divided into three serogroups, namely serogroup B, serogroup I (Intermediate) and serogroup C, and subsequently into 19 different serovars. Worldwide, serogroup B is the most prevalent followed by serogroup I. Clear differences have been observed in the duration of infection and growth kinetics between serovars from different serogroups in murine and cell culture models. Reasons for these observed differences are bacterial and host related, and are not well understood. The aim of this study was to determine the differences in immunoglobulin (Ig) G responses between the three serogroups in a group of patients infected with different serovars. Serovars were assessed from 235 C. trachomatispositive patients and quantitative IgG responses were determined. Analyses of variance were used to compare the IgG responses between the three serogroups. Of the serovars, 46% were B group (with serovar E the most prevalent: 35.3%), 39.6% were I group and 14.3% were C group. A highly significant difference in serologic response was shown when comparing the mean IgG concentrations (AU/mL) of patients having serovars in the most prevalent serogroup compared to the other serogroups: B = 135, C = 46 and I = 60 (B vs. C and B vs. I, P < 0.001). In conclusion, the most prevalent serovars generate the highest serologic responses.

Association between colonization with Group B Streptococcus and preterm delivery: a systematic review.

Up to 36% of pregnant women are colonized with Group B Streptococcus (GBS). Preterm delivery in colonized mothers is a risk factor for early onset neonatal GBS disease, but whether maternal GBS genital colonization is related to preterm delivery is unclear. The objective of this review was to determine the relationship between maternal colonization with GBS and preterm delivery. Pubmed searches and reference lists of all selected publications were used to find studies reporting on the relationship between maternal GBS colonization and preterm delivery. Study characteristics were abstracted, and validity scores were performed. To assess the relationship between GBS colonization and pregnancy outcome, four-fold prognostic tables were constructed for each study. Out of more than 60 full-text articles, 16 follow-up studies and four case control studies were included in this review. Follow-up studies were divided into 'cohort studies,' in which cultures were taken early in pregnancy and which reported on pregnancy outcome, and 'cross-sectional studies', in which cultures were collected during delivery. Studies differed widely in methods, validity score, and GBS prevalence. The combined estimate from a random effect meta-analysis of the 11 cohort studies was 1.06 (95% confidence intervals (CI) 0.95-1.19) and for the five cross-sectional studies 1.75 (95% CI 1.43-2.14). For the case control studies, the pooled odds ratio was 1.59 (95% CI 1.03-2.44). This systematic review did not show an association between maternal GBS colonization during pregnancy and preterm delivery. However, in case of preterm delivery, there is an increased risk of subsequent maternal GBS colonization.

Pharmacokinetics of amoxicillin in maternal, umbilical cord, and neonatal sera.

The pharmacokinetics of amoxicillin were studied in umbilical cord and neonatal sera relative to maternal concentrations in prevention of neonatal group B streptococcus infection. The subjects were 44 pregnant women receiving amoxicillin as 1 or 2 g as an intravenous infusion. To measure the concentrations, blood samples were obtained from the mother, the arterial and venous umbilical cord, and the neonate. The pharmacokinetics were characterized by a five-compartment model by using nonlinear mixed-effects (population) modeling. The population estimates for the clearance, central volume of distribution, and the two peripheral maternal volumes of distribution were 19.7 +/- 0.99 liters/h, 6.40 +/- 0.61 liters, and 5.88 +/- 0.83 liters (mean +/- standard error), respectively. The volume of distribution of the venous umbilical cord and the neonatal volume of distribution were 3.40 liters and 11.9 liters, respectively. The pharmacokinetic parameter estimates were used to simulate the concentration-time profiles in maternal, venous umbilical cord, and neonatal sera. The peak concentration in the venous umbilical cord serum was 18% of the maternal peak concentration. It was reached 3.3 min after the maternal peak concentration. The concentration-time profile in neonatal serum was determined by the profile in venous umbilical cord serum, which in turn depended on the profile in maternal serum. Furthermore, the simulated concentrations in maternal, venous umbilical cord, and neonatal sera exceeded the MIC for group B streptococcus for more than 90% of the 4-h dosing interval. In a first approximation, the 2-g infusion to the mother appears to be adequate for the prevention of group B streptococcal disease. However, to investigate the efficacy of the prophylaxis, further studies of the interindividual variability in pharmacokinetics are indicated.

The influence of labour on the pharmacokinetics of intravenously administered amoxicillin in pregnant women.

AIMS: Many physiological changes take place during pregnancy and labour. These might change the pharmacokinetics of amoxicillin, necessitating adjustment of the dose for prevention of neonatal infections. We investigated the influence of labour on the pharmacokinetics of amoxicillin. METHODS: Pregnant women before and during labour were recruited and treated with amoxicillin intravenously. A postpartum dose was offered. Blood samples were obtained and amoxicillin concentrations were determined using high-pressure liquid chromatography. The pharmacokinetics were characterized by nonlinear mixed-effects modelling using NONMEM. RESULTS: The pharmacokinetics of amoxicillin in 34 patients was best described by a three-compartment model. Moderate interindividual variability was identified in CL, central and peripheral volumes of distribution. The volume of distribution (V) increased with an increasing amount of oedema. Labour influenced the parameter estimate of peripheral volume of distribution (V(2)). V(2) was decreased during labour, and even more in the immediate postpartum period. For all patients the population estimates (mean +/- SE) for CL and V were 21.1 +/- 4.1 l h(-1) (CL), 8.7 +/- 6.6 l (V(1)), 11.8 +/- 7.7 l (V(2)) and 20.5 +/- 15.4 l (V(3)) respectively. CONCLUSIONS: The peripheral distribution volume of amoxicillin in pregnant women during labour and immediately postpartum is decreased. However, these changes are not clinically relevant and do not warrant deviations from the recommended dosing regimen for amoxicillin during labour in healthy pregnant patients.

Lack of alternative coreceptor use by pediatric HIV-1 R5 isolates for infection of primary cord or adult peripheral blood mononuclear cells.

HIV-1 infection of neonates results in an extended acute period of virus replication, frequent neurological problems and reduced survival compared to adults. In adults, R5 viruses mainly infect CCR5(+) CD4(+) memory T-cells. In neonates, CCR5(+) memory T-cells form a substantially smaller fraction of total lymphocytes. We therefore tested whether alternative coreceptors confer infection of lymphocytes by pediatric isolates. Pediatric HIV-1 R5 isolates failed to replicate in Delta32/Delta32 CCR5 PBMCs or in cord PBMCs treated with a CCR5 inhibitor. These results do not indicate a role for alternative coreceptors and provide support for CCR5 inhibitors in the therapy of HIV-1(+) neonates.

Amoxicillin pharmacokinetics in pregnant women with preterm premature rupture of the membranes.

OBJECTIVE: This study was undertaken to study the pharmacokinetics of intravenously administered amoxicillin in pregnant women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN: Healthy women with PPROM were recruited and treated with amoxicillin (2 g initially and 1 g subsequently). Blood samples were obtained from the opposite arm and concentrations determined with the use of high-pressure liquid chromatography. Nonlinear mixed-effects modeling was performed in nonlinear mixed effect (population) modeling. RESULTS: The pharmacokinetics of 17 patients was described by a 3-compartment model. Clearance and volume of distribution at steady state were 22.8 L/h and 21.4 L/h, respectively, similar to values in nonpregnant individuals. There was little variability between patients. No relationship was observed between values of individual pharmacokinetic parameters and various covariates. CONCLUSION: The pharmacokinetics of amoxicillin in pregnant patients with PPROM similar to nonpregnant individuals. Given the small interindividual variability in pharmacokinetics, no dose adjustments are required to account for differences between subjects under normal circumstances.

Morbidity related to maternal group B streptococcal infections.

Group B streptococcus is known to be a leading cause of neonatal infection, but less appreciated is the fact that it causes maternal infection also. Maternal group B streptococcal infections during pregnancy and delivery threaten not only the mother, but the child as well. Postpartum infection, such as mastitis, bacteremia, sepsis, meningitis, endometritis, and wound infections are hazards to the mother. We describe the various maternal group B streptococcal infections, their characteristics, associated neonatal morbidity, and prevention and treatment strategies during pregnancy, delivery, and in the postpartum period.

Description of the ICTI consortium: an integrated approach to the study of Chlamydia trachomatis infection.

The use of an integrated approach to the study of Chlamydia trachomatis infection of the female genital tract, presented at the mini-symposium "Chlamydia trachomatis infections" and described in the thesis of Joseph M. Lyons, has resulted in the creation of the ICTI consortium. The ICTI consortium is based on strong interaction and collaboration between basic scientists, clinicians, epidemiologists, and health care policy makers. This translational approach will help to further the valuable insight into the immunopathogenesis of this sexually transmitted infection (STI) and the development of new intervention strategies, including the vaccines and screening programs necessary to effectively diagnose, treat and prevent C. trachomatis infection. A background of the need for this integrated approach is presented and the goals and participants of the consortium are described.

Routine use of hysterosalpingography prior to laparoscopy in the fertility workup: a multicentre randomized controlled trial.

BACKGROUND: A multicentre randomized controlled trial with or without hysterosalpingography (HSG) was conducted to assess the usefulness of HSG as a routine investigation in the fertility workup prior to laparoscopy and dye. METHODS: From 1 April 1997 to 1 April 2002, subfertile women were allocated by a computer-based 1 : 1 ratio randomization procedure, either for an HSG followed by laparoscopy and dye (the intervention group) of for laparoscopy and dye only (the control group) as a part of their fertility workup. Cumulative pregnancy rate (CPR) within 18 months after randomization was the primary outcome of interest. RESULTS: 344 women were randomized to the intervention group (n = 169) and the control group (n = 175). There was no significant difference in CPR at 18 months in the intervention group (49.1%) [95% confidence interval (CI) 41.6 to 56.6] and the control group (50.3%) (95% CI 42.8 to 57.8), a difference of -1.2% (95% CI -11.8% to 9.5%). CONCLUSION: The routine use of HSG at an early stage in the fertility workup prior to laparoscopy and dye does not influence CPR, compared with the routine use of laparoscopy and dye without HSG.