2021 European guideline on the management of Mycoplasma genitalium infections.

Mycoplasma genitalium infection contributes to 10-35% of non-chlamydial non-gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and pelvic inflammatory disease (PID) in 10-25%. Transmission of M. genitalium occurs through direct mucosal contact. CLINICAL FEATURES AND DIAGNOSTIC TESTS: Asymptomatic infections are frequent. In men, urethritis, dysuria and discharge predominate. In women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal pain and dyspareunia. Symptoms are the main indication for diagnostic testing. Diagnosis is achievable only through nucleic acid amplification testing and must include investigation for macrolide resistance mutations. THERAPY: Therapy for M .genitalium is indicated if M. genitalium is detected. Doxycycline has a cure rate of 30-40%, but resistance is not increasing. Azithromycin has a cure rate of 85-95% in macrolide-susceptible infections. An extended course of azithromycin appears to have a higher cure rate, and pre-treatment with doxycycline may decrease organism load and the risk of macrolide resistance selection. Moxifloxacin can be used as second-line therapy but resistance is increasing. RECOMMENDED TREATMENT: Uncomplicated M. genitalium infection without macrolide resistance mutations or resistance testing: Azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral). Second-line treatment and treatment for uncomplicated macrolide-resistant M. genitalium infection: Moxifloxacin 400 mg od for 7 days (oral). Third-line treatment for persistent M. genitalium infection after azithromycin and moxifloxacin: Doxycycline or minocycline 100 mg bid for 14 days (oral) may cure 40-70%. Pristinamycin 1 g qid for 10 days (oral) has a cure rate of around 75%. Complicated M. genitalium infection (PID, epididymitis): Moxifloxacin 400 mg od for 14 days. MAIN CHANGES FROM THE 2016 EUROPEAN M. GENITALIUM GUIDELINE: Due to increasing antimicrobial resistance and warnings against moxifloxacin use, indications for testing and treatment have been narrowed to primarily involve symptomatic patients. The importance of macrolide resistance-guided therapy is emphasised.

Attachment and symptom reporting in adolescents and young adults after a concussion.

BACKGROUND: The incidence of hospital-treated concussion is 100-300/100,000 person years. Reporting of long-lasting post-concussion symptoms (PCS) is estimated at 5-15%. Attachment insecurity is a potential vulnerability factor for physical illness and poorer disease outcomes in general. This study aimed to explore associations between attachment insecurity and PCS in young people sustaining a concussion. METHODS: This cross-sectional study was embedded in a cohort of 15-30-year-old patients (n = 3080) 3 months after sustaining a concussion. Data were obtained from a database and questionnaires. PCS were measured by the Rivermead Post-Concussion Symptoms Questionnaire and attachment dimensions (anxiety and avoidance) by the Experiences in Close Relationships-Relationship Structures Questionnaire. Multiple linear regression models were performed to investigate the association between the attachment dimensions and PCS with adjustment for demographic, injury-related and psychological factors and with additional testing for interaction between the attachment dimensions. RESULTS: In the final study sample, comprising 973 patients (31.6%), we found an interaction between the attachment dimensions. Hence, the effect of attachment anxiety on PCS was statistically insignificant at low avoidance (25th percentile) but significant at high avoidance (75th percentile, ß = 0.64 (95%CI: 0.02; 1.26)), whereas the effect of attachment avoidance was significant regardless of level of attachment anxiety (25th percentile, ß = 1.09 (95%CI: 0.18; 2.01); 75th percentile, ß = 2.71 (95%CI: 1.80; 3.61)). CONCLUSION: Attachment insecurity, especially characterised by high avoidance in combination with high anxiety, also called fearful attachment, is associated with PCS. Considering the attachment perspective can potentially improve health care for this patient group.

Macrolide resistance in Mycoplasma genitalium in Catalonia, Spain: a 1 year prospective study.

BACKGROUND: Mycoplasma genitalium is an emergent cause of sexually transmitted disease (STD). The first-line treatment is azithromycin, but macrolide resistance is increasing due to mutations in the 23S rRNA gene. OBJECTIVES: To determine the rates of M. genitalium infection and macrolide resistance in an area adjacent to Barcelona. METHODS: This 1 year prospective study was performed in a heterogenous population that included both low- and high-risk patients. M. genitalium was detected in all specimens sent to our institution for STD detection. Epidemiological and relevant clinical data were collected in the positive cases. Characterization of macrolide-associated resistance was performed by 23S rDNA sequencing. RESULTS: Of the 3540 patients included, 132 (3.7%) were positive for M. genitalium. Another sexually transmitted bacteria was detected in 20.4% of the M. genitalium cases, and Chlamydia trachomatis (11%) was the most frequently co-detected microorganism. Only 61.4% of patients received an adequate initial treatment against M. genitalium. The test of cure (TOC) was performed in 42% of patients, and therapeutic failure was detected in 10 cases. The rate of macrolide resistance was 12.6% and the most prevalent mutation was A2058G. There was an association between macrolide resistance and a previous history of M. genitalium detection (P < 0.001). CONCLUSIONS: Our results support the contribution of the previous use of macrolides in resistant strains. Given the difficulties in performing TOC in all patients, the inclusion of macrolide resistance in the detection test should be mandatory.

Background review for the '2020 European guideline for the diagnosis and treatment of gonorrhoea in adults'.

Gonorrhoea is a major public health concern globally. Increasing incidence and sporadic ceftriaxone-resistant cases, including treatment failures, are growing concerns. The 2020 European gonorrhoea guideline provides up-to-date evidence-based guidance regarding the diagnosis and treatment of gonorrhoea. The updates and recommendations emphasize significantly increasing gonorrhoea incidence; broad indications for increased testing with validated and quality-assured nucleic acid amplification tests (NAATs) and culture; dual antimicrobial therapy including high-dose ceftriaxone and azithromycin (ceftriaxone 1 g plus azithromycin 2 g) OR ceftriaxone 1 g monotherapy (ONLY in well-controlled settings, see guideline for details) for uncomplicated gonorrhoea when the antimicrobial susceptibility is unknown; recommendation of test of cure (TOC) in all gonorrhoea cases to ensure eradication of infection and identify resistance; and enhanced surveillance of treatment failures when recommended treatment regimens have been used. Improvements in access to appropriate testing, test performance, diagnostics, antimicrobial susceptibility surveillance and treatment, and follow-up of gonorrhoea patients are essential in controlling gonorrhoea and to mitigate the emergence and/or spread of ceftriaxone resistance and multidrug-resistant and extensively drug-resistant gonorrhoea. This review provides the detailed background, evidence base and discussions, for the 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults (Unemo M, et al. Int J STD AIDS. 2020).

2020 European guideline for the diagnosis and treatment of gonorrhoea in adults.

Gonorrhoea is a major public health concern globally. Increasing incidence and sporadic ceftriaxone-resistant cases, including treatment failures, are growing concerns. The 2020 European gonorrhoea guideline provides up-to-date evidence-based guidance regarding the diagnosis and treatment of gonorrhoea. The updates and recommendations emphasize significantly increasing gonorrhoea incidence; broad indications for increased testing with validated and quality-assured nucleic acid amplification tests and culture; dual antimicrobial therapy including high-dose ceftriaxone and azithromycin (ceftriaxone 1 g plus azithromycin 2 g) OR ceftriaxone 1 g monotherapy (ONLY in well-controlled settings, see guideline for details) for uncomplicated gonorrhoea when the antimicrobial susceptibility is unknown; recommendation of test of cure (TOC) in all gonorrhoea cases to ensure eradication of infection and identify resistance; and enhanced surveillance of treatment failures when recommended treatment regimens have been used. Improvements in access to appropriate testing, test performance, diagnostics, antimicrobial susceptibility surveillance and treatment, and follow-up of gonorrhoea patients are essential in controlling gonorrhoea and to mitigate the emergence and/or spread of ceftriaxone resistance and multidrug-resistant and extensively drug-resistant gonorrhoea. For detailed background, evidence base and discussions, see the background review for the present 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults (Unemo M, et al. Int J STD AIDS. 2020).

"Understand your illness and your needs": Assessment-informed patient education for people with multiple functional somatic syndromes.

OBJECTIVES: Patients suffering from multiple functional somatic syndromes (FSS) such as fibromyalgia, chronic fatigue syndrome, or irritable bowel syndrome, often lack both a clear diagnosis and tangible illness explanations, which is a barrier for treatment engagement. We tested a short-term intervention taking the unifying concept of Bodily Distress Syndrome (BDS) as a point of departure. The intervention consisted of a clinical assessment, group-based patient education, and one follow-up consultation. METHODS: 174 patients were included and received questionnaires at baseline, after clinical assessment, after patient education, and median 19 weeks after baseline. Data were analyzed using random effects models and simple t-tests. Qualitative data were thematically analyzed. RESULTS: We found small reductions in symptom levels, considerable reductions in illness worry, and improvement of illness perceptions and illness-related behaviors. Overall, patients evaluated the intervention positively and expressed high expectations for further treatment. Qualitative results mainly supported these findings. CONCLUSION: Targeting illness perceptions through patient education is crucial to obtain patient engagement in self-help management or further treatment. This may lead to improved outcomes. PRACTICAL IMPLICATIONS: Physicians in primary and secondary care should strive to give patients with multiple FSS a clear understanding that their various FSS diagnoses are related and provide tangible illness explanations.

Should we be testing for urogenital Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum in men and women? - a position statement from the European STI Guidelines Editorial Board.

At present, we have no evidence that we are doing more good than harm detecting and subsequently treating Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum colonizations/infections. Consequently, routine testing and treatment of asymptomatic or symptomatic men and women for M. hominis, U. urealyticum and U. parvum are not recommended. Asymptomatic carriage of these bacteria is common, and the majority of individuals do not develop any disease. Although U. urealyticum has been associated with urethritis in men, it is probably not causal unless a high load is present (likely carriage in 40-80% of detected cases). The extensive testing, detection and subsequent antimicrobial treatment of these bacteria performed in some settings may result in the selection of antimicrobial resistance, in these bacteria, 'true' STI agents, as well as in the general microbiota, and substantial economic cost for society and individuals, particularly women. The commercialization of many particularly multiplex PCR assays detecting traditional non-viral STIs together with M. hominis, U. parvum and/or U. urealyticum has worsened this situation. Thus, routine screening of asymptomatic men and women or routine testing of symptomatic individuals for M. hominis, U. urealyticum and U. parvum is not recommended. If testing of men with symptomatic urethritis is undertaken, traditional STI urethritis agents such as Neisseria gonorrhoeae, Chlamydia trachomatis, M. genitalium and, in settings where relevant, Trichomonas vaginalis should be excluded prior to U. urealyticum testing and quantitative species-specific molecular diagnostic tests should be used. Only men with high U. urealyticum load should be considered for treatment; however, appropriate evidence for effective treatment regimens is lacking. In symptomatic women, bacterial vaginosis (BV) should always be tested for and treated if detected.

Cardiac repolarization and depolarization in people with Type 1 diabetes with normal ejection fraction and without known heart disease: a case-control study.

AIMS: To investigate depolarization and repolarization durations in people with Type 1 diabetes, including the relationship to age. METHODS: 855 persons with Type 1 diabetes without known heart disease were included and matched with 1710 participants from a general population study. Clinical examinations, questionnaires and biochemistry were assessed. A 10-second 12-lead ECG was performed and analysed digitally. RESULTS: QTc was longer in people with Type 1 diabetes compared to controls (414±16 vs. 411±19 ms, P <0.001), and particularly so in young people with Type 1 diabetes. The fully adjusted increase was 13.8 ms (95% confidence interval (CI): 8.6-19.0 ms, P <0.001) at age 20 years and 3.4 ms (CI: 1.5-5.3 ms, P<0.001) at age 40 years. The rate-corrected QRSc was increased in people with Type 1 diabetes (97±11 vs. 95±11 ms, P <0.001) and was age-independent (P =0.5). JTc was increased in the young people with Type 1 diabetes (10.7 ms (CI: 5.4-16.0 ms, P <0.001) at age 20 years), but not in older people with Type 1 diabetes (interaction age-diabetes, P <0.01). CONCLUSIONS: For people with Type 1 diabetes, cardiac depolarization is increased at all ages, whereas repolarization is increased only relatively in young people with Type 1 diabetes. Hence, young people with Type 1 diabetes may be more prone to ventricular arrhythmias. The findings contribute to the understanding of sudden cardiac death in young people with Type 1 diabetes.

In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains.

Background: Mycoplasma genitalium is estimated to be the second most common cause of bacterial sexually transmitted infection in Europe. It is of increasing public health concern due to the rapid development of resistance to different antimicrobial classes, including the preferred first- and second-line treatments azithromycin and moxifloxacin. Thus, new antimicrobial agents are urgently needed, especially for the treatment of MDR strains. Methods: The in vitro activity of the new spiropyrimidinetrione zoliflodacin against 47 M. genitalium strains was assessed by growing M. genitalium in Vero cell culture and measuring growth by quantitative PCR. The collection included 34 moxifloxacin-susceptible (MIC <1 mg/L) and 13 moxifloxacin-resistant (MIC ≥1 mg/L) strains. Twenty-three of the strains were azithromycin resistant (MIC ≥16 mg/L) and 12 of these strains were MDR. Results: Only one (2.1%) strain with substantially increased MIC (4 mg/L) and potential resistance to zoliflodacin was found. Zoliflodacin was overall more potent than moxifloxacin (P = 0.009) and no cross-resistance was observed between the two drug classes of topoisomerase II inhibitors. Differences in the MICs of zoliflodacin and azithromycin were not statistically significant; however, 23 (48.9%) compared with potentially 1 (2.1%) of the strains were resistant to azithromycin and zoliflodacin, respectively. Conclusions: Zoliflodacin is a promising candidate for the treatment of M. genitalium and it is important to further develop and evaluate this drug.

Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway and Sweden in 2016.

OBJECTIVES: Mycoplasma genitalium (MG) causes urethritis and cervicitis, potentially causing reproductive complications. Resistance in MG to first-line (azithromycin) and second-line (moxifloxacin) treatment has increased. We examined the clinical and analytical performance of the new Conformité Européene (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic); the prevalence of MG, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and MG resistance to azithromycin and moxifloxacin in Denmark, Norway and Sweden in 2016. METHODS: From February 2016 to February 2017, urogenital and extragenital (only in Denmark) specimens from consecutive attendees at three sexually transmitted disease clinics were tested with the CE/IVD AMG, the research-use-only MG Alt TMA-1 assay (Hologic), Aptima Combo 2 (CT/NG) assay and a laboratory-developed TaqMan real-time mgpB quantitative real-time PCR (qPCR). Resistance-associated mutations were determined by sequencing. Strains of MG and other mycoplasma species in different concentrations were also tested. RESULTS: In total 5269 patients were included. The prevalence of MG was 7.2% (382/5269; 4.9-9.8% in the countries). The sensitivity of the CE/IVD AMG, MG Alt TMA-1 and mgpB qPCR ranged 99.13-100%, 99.13-100% and 73.24-81.60%, respectively, in the countries. The specificity ranged 99.57-99.96%, 100% and 99.69-100%, respectively. The prevalence of resistance-associated mutations for azithromycin and moxifloxacin was 41.4% (120/290; 17.7-56.6%) and 6.6% (18/274; 4.1-10.2%), respectively. Multidrug resistance was found in all countries (2.7%; 1.1-4.2%). CONCLUSIONS: Both transcription-mediated amplification (TMA)-based MG assays had a highly superior sensitivity compared to the mgpB qPCR. The prevalence of MG and azithromycin resistance was high. Validated and quality-assured molecular tests for MG, routine resistance testing of MG-positive samples and antimicrobial resistance surveillance are crucial.

Low adiponectin levels at baseline and decreasing adiponectin levels over 10 years of follow-up predict risk of the metabolic syndrome.

AIM: Adiponectin is the most abundant adipokine and may play a key role in the interplay between obesity, inflammation, insulin resistance and the metabolic syndrome (MetS). Thus, this large population-based cohort investigated whether adiponectin at baseline and/or a decrease in adiponectin during follow-up is associated prospectively with the risk of incident MetS. METHODS: Using a prospective study design, the development of MetS was examined in 1134 healthy participants from the community. Plasma adiponectin was measured at study entry and again after a median follow-up of 9.4 years (IQR: 9.2-9.7). During follow-up, 187 participants developed MetS, and 439 presented with at least two components of MetS. RESULTS: During follow-up, adiponectin decreased in participants who developed MetS, whereas adiponectin was increased in those who did not develop MetS (P<0.001). Those with low adiponectin levels (quartile 1) at baseline had an increased risk of developing MetS (OR: 2.92, 2.08-6.97; P<0.001) compared with those with high levels (quartile 4). After adjusting for confounding variables, low adiponectin levels at baseline remained independently associated with MetS (OR: 2.24, 1.11-4.52; P=0.017). Similarly, participants with a decrease in adiponectin during follow-up also had an increased risk of MetS (OR: 2.96, 2.09-4.18; P<0.001). This association persisted after multivariable adjustments, including for baseline adiponectin (OR: 4.37, 2.77-6.97; P<0.001). Finally, adiponectin levels at follow-up were inversely associated with an increase in the number of components of MetS (P<0.001); geometric mean adiponectin levels were 9.5mg/L (95% CI: 9.0-10.0) for participants with no components vs 7.0mg/L (95% CI: 6.3-7.9) for those with four to five components. CONCLUSIONS/INTERPRETATION: Low plasma adiponectin levels at baseline and decreasing adiponectin levels during follow-up are both associated with an increased risk of MetS.

High and low vitamin D level is associated with cardiovascular autonomic neuropathy in people with Type 1 and Type 2 diabetes.

AIM: To investigate the possible association between vitamin D deficiency and cardiovascular autonomic neuropathy in people with diabetes. METHODS: A total of 113 people with Type 1 or Type 2 diabetes [mean (interquartile range) diabetes duration 22.0 (12-31) years, mean (sd) age 56.2 (13.0) years, 58% men] underwent vitamin D (D2 and D3) assessment, and were screened for cardiovascular autonomic neuropathy using three cardiovascular reflex tests [heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva manoeuvre] and assessment of 5-min resting heart rate and heart rate variability indices. RESULTS: We found an inverse U-shaped association between serum vitamin D level and E/I ratio, 30/15 ratio and three heart rate variability indices (P < 0.05). Vitamin D level was non-linearly associated with cardiovascular autonomic neuropathy diagnosis (P < 0.05 adjusted for age and sex). Linear regression models showed that an increase in vitamin D level from 25 to 50 nmol/l was associated with an increase of 3.9% (95% CI 0.1;7.9) in E/I ratio and 4.8% (95% CI 4.7;9.3) in 30/15 ratio. Conversely, an increase from 125 to 150 nmol/l in vitamin D level was associated with a decrease of 2.6% (95% CI -5.8;0.1) and 4.1% (95% CI -5.8;-0.5) in the respective outcome measures. CONCLUSIONS: High and low vitamin D levels were associated with cardiovascular autonomic neuropathy in people with diabetes. Future studies should explore this association and the efficacy of treating dysvitaminosis D to prevent cardiovascular autonomic neuropathy.

Chlamydia related bacteria (Chlamydiales) in early pregnancy: community-based cohort study.

OBJECTIVES: Serological case-control studies suggest that certain chlamydia-related bacteria (Chlamydiales) which cause cows to abort may do the same in humans. Chlamydiales include Waddlia chondrophila, Chlamydia abortus and Chlamydia trachomatis. Data on prevalence of Chlamydiales in pregnancy are sparse. Using stored urine samples from a carefully characterised cohort of 847 newly pregnant women recruited from 37 general practices in London, UK, we aimed to investigate the prevalence and types of Chlamydiales infections. We also explored possible associations with miscarriage or spontaneous preterm birth. METHODS: Samples were tested using W. chondrophila and pan-Chlamydiales specific real-time PCRs targeting the 16S rRNA gene. Samples positive on either PCR were subjected to DNA sequencing and C. trachomatis PCR. RESULTS: The overall prevalence of Chlamydiales was 4.3% (36/847, 95% CI 3.0% to 5.8%). The prevalence of W. chondrophila was 0.6% (n = 5), C. trachomatis 1.7% (n = 14), and other Chlamydiales species 2.0% (n = 17). Infection with C. trachomatis was more common in women aged <25, of black ethnicity or with bacterial vaginosis, but this did not apply to W. chondrophila or other Chlamydiales. Follow up was 99.9% at 16 weeks gestation and 90% at term. No infection was significantly associated with miscarriage at ≤12 weeks (prevalence 10%, 81/827) or preterm birth <37 weeks (prevalence 4%, 23/628). Of 25 samples sequenced, seven (28%) were positive for Chlamydiales bacterium sequences associated with respiratory tract infections in children. CONCLUSION: In the first study to use the pan-Chlamydiales assay on female urine samples, 4% of pregnant women tested positive for Chlamydiales, including species known to be pathogenic in mothers and neonates.

Background review for the 2016 European guideline on Mycoplasma genitalium infections.

Mycoplasma genitalium is a cause of 10-35% of non-chlamydial non-gonococcal urethritis in men and in women, and is associated with cervicitis and pelvic inflammatory disease (PID). Transmission of M. genitalium occurs through direct mucosal contact. In women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal pain and dyspareunia. In men, urethritis, dysuria and discharge predominates. Asymptomatic infections are frequent. In this review, we present the evidence base for the recommendations in the 2016 European guideline on M. genitalium infections and describe indications for testing, recommended diagnostic methods, treatment and patient management. The guideline was prepared on behalf of the European branch of The International Union against Sexually Transmitted Infections; the European Academy of Dermatology and Venereology; the European Dermatology Forum; the European Society of Clinical Microbiology and Infectious Diseases; the Union of European Medical Specialists. The European Centre for Disease Prevention and Control and the European Office of the World Health Organisation also contributed to their development.

2016 European guideline on Mycoplasma genitalium infections.

Mycoplasma genitalium infection contributes to 10-35% of non-chlamydial non-gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and pelvic inflammatory disease (PID). Transmission of M. genitalium occurs through direct mucosal contact. Asymptomatic infections are frequent. In women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal pain and dyspareunia. In men, urethritis, dysuria and discharge predominates. Besides symptoms, indication for laboratory test is a high-risk sexual behaviour. Diagnosis is achievable only through nucleic acid amplification testing (NAAT). If available, NAAT diagnosis should be followed with an assay for macrolide resistance. Therapy for M. genitalium is indicated if M. genitalium is detected or on an epidemiological basis. Doxycycline has a low cure rate of 30-40%, but does not increase resistance. Azithromycin has a cure rate of 85-95% in macrolide susceptible infections. An extended course appears to have a higher cure rate. An increasing prevalence of macrolide resistance, most likely due to widespread use of azithromycin 1 g single dose without test of cure, is drastically decreasing the cure rate. Moxifloxacin can be used as second-line therapy, but resistance is increasing. Uncomplicated M. genitalium infection should be treated with azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral), or josamycin 500 mg three times daily for 10 days (oral). Second line treatment and treatment for uncomplicated macrolide resistant M. genitalium infection is moxifloxacin 400 mg od for 7-10 days (oral). For third line treatment of persistent M. genitalium infection after azithromycin and moxifloxacin doxycycline 100 mg two times daily for 14 days can be tried and may cure 30%. Pristinamycin 1 g four times daily for 10 days (oral) has a cure rate of app. 90%. Complicated M. genitalium infection (PID, epididymitis) is treated with moxifloxacin 400 mg od for 14 days.

Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients.

STUDY QUESTION: What is the diagnostic performance of qPCR assays compared with Nugent scoring for abnormal vaginal microbiota and for predicting the success rate of IVF treatment? SUMMARY ANSWER: The vaginal microbiota of IVF patients can be characterized with qPCR tests which may be promising tools for diagnosing abnormal vaginal microbiota and for prediction of clinical pregnancy in IVF treatment. WHAT IS KNOWN ALREADY: Bacterial vaginosis (BV) is a common genital disorder with a prevalence of approximately 19% in the infertile population. BV is often sub-clinical with a change of the vaginal microbiota from being Lactobacillus spp. dominated to a more heterogeneous environment with anaerobic bacteria, such as Gardnerella vaginalis and Atopobium vaginae. Few studies have been conducted in infertile women, and some have suggested a negative impact on fecundity in the presence of BV. STUDY DESIGN, SIZE, DURATION: A cohort of 130 infertile patients, 90% Caucasians, attending two Danish fertility clinics for in vitro fertilization (IVF) treatment from April 2014-December 2014 were prospectively enrolled in the trial. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Vaginal swabs from IVF patients were obtained from the posterior fornix. Gram stained slides were assessed according to Nugent's criteria. PCR primers were specific for four common Lactobacillus spp., G. vaginalis and A. vaginae. Threshold levels were established using ROC curve analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of BV defined by Nugent score was 21% (27/130), whereas the prevalence of an abnormal vaginal microbiota was 28% (36/130) defined by qPCR with high concentrations of Gardnerella vaginalis and/or Atopobium vaginae. The qPCR diagnostic approach had a sensitivity and specificity of respectively 93% and 93% for Nugent-defined BV. Furthermore, qPCR enabled the stratification of Nugent intermediate flora. Eighty-four patients completed IVF treatment. The overall clinical pregnancy rate was 35% (29/84). Interestingly, only 9% (2/22) with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (P = 0.004). LIMITATIONS, REASONS FOR CAUTION: Although a total of 130 IVF patients were included in the study, a larger sample size is needed to draw firm conclusions regarding the possible adverse effect of an abnormal vaginal microbiota in relation to the clinical pregnancy rate and other reproductive outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Abnormal vaginal microbiota may negatively affect the clinical pregnancy rate in IVF patients. If a negative correlation between abnormal vaginal microbiota and the clinical pregnancy rate is corroborated, patients could be screened and subsequently treated for abnormal vaginal microbiota prior to fertility treatment. STUDY FUNDING/COMPETING INTERESTS: This study was funded by The AP Møller Maersk Foundation for the advancement of Medical Science and Hospital of Central Jutland Research Fund, Denmark. No competing interests. TRIAL REGISTRATION NUMBER: The project was registered at clinicaltrials.gov (file number NCT02042352).

Acceptance and commitment group therapy (ACT-G) for health anxiety: a randomized controlled trial.

BACKGROUND: Severe health anxiety is frequent and costly, yet rarely diagnosed or treated. Earlier treatment studies show problems with recruitment, dropout and recovery. In the current study, the authors aimed to test the effect of acceptance and commitment group therapy (ACT-G) compared to waitlist in patients with severe health anxiety. METHOD: During March 2010 to April 2012, 126 consecutively referred patients meeting research criteria for severe health anxiety were block-randomized (1:1) to ACT-G or a 10 months' waitlist (Clinicaltrials.gov, no. NCT01158430). Patients allocated to ACT-G were treated in seven groups of nine patients between December 2010 and October 2012 and received nine weekly 3-h group sessions and a booster session consisting of ACT techniques. The primary outcome was decided a priori as the mean change in self-reported illness worry on the Whiteley-7 Index (WI) from baseline to 10 months' follow-up. Secondary outcomes were improvement in emotional distress and health-related quality of life at 10 months' follow-up. RESULTS: Intention-to-treat analysis showed a statistically significant mean difference of 20.5 points [95% confidence interval (CI) 11.7-29.4, p < 0.001] on the WI between the groups at 10 months, and the between-group effect sizes were large (Cohen's d = 0.89, 95% CI 0.50-1.29). The number needed to treat was 2.4 (95% CI 1.4-3.4, p < 0.001). Diagnosis and treatment were well accepted by the patients. CONCLUSIONS: ACT-G seems feasible, acceptable and effective in treating severe health anxiety.