Use of Home-Based Self-Collected Dried Blood Spots to Test for Syphilis, Human Immunodeficiency Virus, Hepatitis C and B Virus Infections and Measuring Creatinine Concentration.

INTRODUCTION: Home-based self-collected dried blood spot (DBS) sampling could simplify sexual health and preexposure prophylaxis care and reduce sexually transmitted infections (STIs) clinic visits for men who have sex with men (MSM). We compared the performance of DBS to venipuncture collected blood samples to test four STIs and creatinine concentration. METHODS: We invited MSM clients of the Amsterdam STI clinic to participate. Routinely collected peripheral blood was tested for syphilis treponemal antibody, HIV (HIV Ag/Ab), HCV (antibodies), HBV (HBsAg) and creatinine concentration. Participants received a home kit for DBS sampling, a return envelope and a questionnaire to evaluate the acceptability, feasibility and usability of DBS, measured on 5-point Likert scales, 1 representing complete disagreement and 5 complete agreement. We assessed sensitivity and specificity of DBS versus peripheral blood-based testing. RESULTS: In 2020 to 2021, we included 410 participants; 211 (51.5%) returned a completed DBS card, 117 (28.5%) returned a partially filled card and 82 (20.0%) did not return a card. The sensitivity for syphilis was 90.8% and the specificity 84.3%. For both HIV Ag/Ab and HBsAg, the sensitivity and specificity were 100.0%. The sensitivity for HCV antibody was 80.0%, and the specificity was 99.2%. The DBS creatinine concentration was a mean of 5.3 µmol/L higher than in venipuncture obtained plasma. Participants' median willingness to take a future DBS was 4 (interquartile range, 3-5). DISCUSSION: Dried blood spot may be an acceptable method among MSM for STI testing and creatinine follow-up during preexposure prophylaxis use. However, collecting enough blood on DBS cards was a challenge, and sensitivities for syphilis and HCV serology were too low.

Detection of Treponema pallidum DNA During Early Syphilis Stages in Peripheral Blood, Oropharynx, Ano-Rectum and Urine as a Proxy for Transmissibility.

BACKGROUND: Syphilis diagnosis may be challenging, especially in the asymptomatic and early clinical stages. We evaluated the presence of Treponema pallidum DNA (TP-DNA) in various sample types to elucidate transmissibility during various syphilis stages. METHODS: The study was conducted at the Amsterdam Centre for Sexual Health. We included adult men who have sex with men (MSM), who were suspected of having syphilis. The 2020 European guidelines definitions were followed for the diagnosis and staging of syphilis. Using a polymerase chain reaction (PCR) targeting the polA gene of Treponema pallidum (TP-PCR), we tested the following study samples on TP-DNA: peripheral blood, oropharyngeal swab, ano-rectal swab, and urine. RESULTS: From November 2018 to December 2019 we included 293 MSM. Seventy clients had primary syphilis, 73 secondary syphilis, 86 early latent syphilis, 14 late latent syphilis, 23 treated syphilis, and 27 had no syphilis. TP-DNA was detected in at least 1 study sample in 35/70 clients with primary syphilis (2/70 peripheral blood, 7/70 oropharynx, 13/70 ano-rectum, and 24/70 urine); in 62/73 clients with secondary syphilis (15/73 peripheral blood, 47/73 oropharynx, 37/73 ano-rectum, and 26/73 urine); and in 29/86 clients with early latent syphilis (5/86 peripheral blood, 21/86 oropharynx, 11/86 ano-rectum, and 6/86 urine). TP-DNA was not detected in clients with late latent syphilis or treated syphilis, nor in clients without syphilis. CONCLUSIONS: TP-DNA was frequently detected in various sample types in the absence of lesions. This is in line with the high transmission rate of syphilis and opens diagnostic opportunities for early presymptomatic syphilis stages.

Diagnostic performance of the ZEUS Borrelia VlsE1/pepC10 assay in European LB patients: a case-control study.

This retrospective case-control study assesses the sensitivity, specificity, and area under the curve of the ZEUS Borrelia VlsE1/pepC10 assay in comparison with the C6-ELISA in European patients with Lyme borreliosis, healthy blood donors, and potentially cross-reactive controls. We included a convenience series of 161 sera from patients with physician-confirmed early localized or disseminated Lyme borreliosis (n = 143), 400 sera from healthy blood donors and 44 sera with potentially cross-reactive antibodies, on which we performed the aforementioned serological assays and the recomLine immunoblot. Diagnostic parameters were compared in various single-tier and two-tier algorithms. The specificities of the C6-ELISA and the ZEUS Borrelia VlsE1/pepC10 were comparable in healthy blood donors (e.g., single-tier permissive: C6: 362/400, 90.5% [87.2-93.2]; VlsE1/pepC10: 361/400, 90.3% [86.9-93.0]). The C6-ELISA had an apparently higher sensitivity in EM sera (e.g., both time points combined: C6: 61/76, 80.3% [69.5-88.5]; VlsE1/pepC10: 54/76, 71.1% [59.5-80.9]), but these differences were all not-significant. Interestingly, the VlsE1/pepC10 assay had a significantly higher specificity in sera with potentially cross-reactive antibodies (e.g., single-tier permissive: C6: 34/44, 77.3% [62.2-88.5]; VlsE1/pepC10: 40/44, 90.9% [78.3-97.5]; p = 0.031). While the areas under the curve for both assays were excellent, that of the C6-ELISA exceeded that of the VlsE1/pepC10 (C6: AUC = 0.925; VlsE1/pepC10: AUC = 0.878; p = 0.003). The novel ZEUS Borrelia VlsE1/pepC10 assay has generally comparable diagnostic parameters to the C6-ELISA with potentially improved specificity in cross-reactive sera. Thus, it is a useful tool for the serodiagnosis of Lyme borreliosis in Europe.

[Exchange of information between psychiatrist and pharmacist concerning uncollected medication]. / Informatie-uitwisseling tussen psychiater en apotheker over niet-opgehaalde medicatie.

Background Non- compliance with drug regimens has a negative effect on symptomatology and is the largest predictor of relapse in people with Severe Psychiatric Disorder (EPA). When care providers are informed in good time that medication has not been collected and can act on it, compliance can be increased. Aim Assessment of usefulness and feasibility of a system for the Signaling and Reporting by Pharmacists of Uncollected Medication for people with an EPA (Dutch: 'SMANOM-EPA') within the current legal context. Method The package of requirements was drawn up on the basis of questionnaires and telephone interviews with psychiatrists and pharmacists and focus group meetings with patients and significant others. Lawyers and ICT professionals were consulted to formulate the legal and technical preconditions. Results All parties involved considered SMANOM-EPA to be useful. The administrative burden was a determining factor for the feasibility and transparency was an important precondition. The exchange of information could take place securely with existing technology, despite the variation in prescribing and issuing systems. However, opinions were divided as to whether informing and documenting is sufficient or whether consent is necessary. Conclusion The GDPR and the WBGO safeguard patients' rights regarding the use of personal data. Uncertainty about the legal framework and technological possibilities add to the complexity of innovations to promote the exchange of information between practitioners, while the added value is seen by those involved and in comparable innovations. Tijdschrift voor Psychiatrie 63(2021)1, 32-38.

Diagnostic parameters of modified two-tier testing in European patients with early Lyme disease.

Modified two-tier testing (MTTT) for Lyme borreliosis (i.e. confirmation with an EIA instead of an immunoblot) has been shown to have improved sensitivity compared with standard two-tier testing (STTT) in samples from American patients, without losing specificity. The current study assesses the sensitivity and specificity of various algorithms of MTTT in European patients with erythema migrans (EM) as a model disease for early Lyme borreliosis, and in appropriate controls. Four different immunoassays were used in the first tier, followed by either an immunoblot or the C6-EIA, or were used as standalone single-tier test. These tests were performed on consecutively collected sera of 228 Dutch patients with physician-diagnosed EM in the setting of general practice, 231 controls from the general population, and 50 controls with potentially cross-reactive antibodies. All the variants of MTTT that were studied had significantly higher sensitivity compared with their equivalent STTT, while retaining comparable specificity. Within the MTTT algorithms, classifying equivocal results as positive yielded better diagnostic parameters than classifying equivocal results as negative. The best diagnostic parameters were found using the Enzygnost-2 assay in the first tier, followed by a C6-ELISA in the second tier (sensitivity 77.6%, 95% CI 71.7-82.9; specificity 96.1%, 95% CI 92.7-98.2). This algorithm performed significantly better than the equivalent STTT algorithm in terms of sensitivity (p < 0.001), while maintaining comparable specificity (population controls p = 0.617). Our results show that MTTT can be a useful tool for the serodiagnosis of European patients with early Lyme borreliosis.

Effect of vaccination on severity and infectiousness of measles during an outbreak in the Netherlands, 2013-2014.

An outbreak of measles in the Netherlands in 2013-2014 provided an opportunity to assess the effect of MMR vaccination on severity and infectiousness of measles.Measles is notifiable in the Netherlands. We used information on vaccination, hospitalisation, complications, and most likely source(s) of infection from cases notified during the outbreak. When a case was indicated as a likely source for at least one other notified case, we defined it as infectious. We estimated the age-adjusted effect of vaccination on severity and infectiousness with logistic regression.Of 2676 notified cases, 2539 (94.9%) were unvaccinated, 121 (4.5%) were once-vaccinated and 16 (0.6%) were at least twice-vaccinated; 328 (12.3%) cases were reported to have complications and 172 (6.4%) cases were hospitalised. Measles in twice-vaccinated cases led less often to complications and/or hospitalisation than measles in unvaccinated cases (0% and 14.5%, respectively, aOR 0.1 (95% CI 0-0.89), P = 0.03). Of unvaccinated, once-vaccinated and twice-vaccinated cases, respectively, 194 (7.6%), seven (5.1%) and 0 (0%) were infectious. These differences were not statistically significant (P > 0.05).Our findings suggest a protective effect of vaccination on the occurrence of complications and/or hospitalisation as a result of measles and support the WHO recommendation of a two-dose MMR vaccination schedule.

Differential insular cortex subregional vulnerability to α-synuclein pathology in Parkinson's disease and dementia with Lewy bodies.

AIM: The insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), it reveals α-synuclein pathology in advanced stages. The aim of this study is to assess the insular cortex cellular and subregional vulnerability to α-synuclein pathology in well-characterized PD and DLB subjects. METHODS: We analysed postmortem insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB and age-matched controls. The load and distribution of α-synuclein pathology and tyrosine hydroxylase (TH) cells were studied throughout the insular subregions. The selective involvement of von Economo neurons (VENs) in the anterior insula and astroglia was assessed in all groups. RESULTS: A decreasing gradient of α-synuclein pathology load from the anterior periallocortical agranular towards the intermediate dysgranular and posterior isocortical granular insular subregions was found. Few VENs revealed α-synuclein inclusions while astroglial synucleinopathy was a predominant feature in PDD and DLB. TH neurons were predominant in the agranular and dysgranular subregions but did not reveal α-synuclein inclusions or significant reduction in density in patient groups. CONCLUSIONS: Our study highlights the vulnerability of the anterior agranular insula to α-synuclein pathology in PD, PDD and DLB. Whereas VENs and astrocytes were affected in advanced disease stages, insular TH neurons were spared. Owing to the anterior insula's affective, cognitive and autonomic functions, its greater vulnerability to pathology indicates a potential contribution to nonmotor deficits in PD and DLB.

IgG is elevated in obese white adipose tissue but does not induce glucose intolerance via Fcγ-receptor or complement.

BACKGROUND/OBJECTIVES: In obesity, B cells accumulate in white adipose tissue (WAT) and produce IgG, which may contribute to the development of glucose intolerance. IgG signals by binding to Fcγ receptors (FcγR) and by activating the complement system. The aim of our study was to investigate whether activation of FcγR and/or complement C3 mediates the development of high-fat diet-induced glucose intolerance. METHODS: We studied mice lacking all four FcγRs (FcγRI/II/III/IV-/-), only the inhibitory FcγRIIb (FcγRIIb-/-), only the central component of the complement system C3 (C3-/-), and mice lacking both FcγRs and C3 (FcγRI/II/III/IV/C3-/-). All mouse models and wild-type controls were fed a high-fat diet (HFD) for 15 weeks to induce obesity. Glucose metabolism was assessed and adipose tissue was characterized for inflammation and adipocyte functionality. RESULTS: In obese WAT of wild-type mice, B cells (+142%, P<0.01) and IgG (+128% P<0.01) were increased compared to lean WAT. Macrophages of FcγRI/II/III/IV-/-mice released lower levels of cytokines compared to wild-type mice upon IgG stimulation. Only C3-/- mice showed reduced HFD-induced weight gain as compared to controls (-18%, P<0.01). Surprisingly, FcγRI/II/III/IV-/- mice had deteriorated glucose tolerance (AUC +125%, P<0.001) despite reduced leukocyte number (-30%, P<0.05) in gonadal WAT (gWAT), whereas glucose tolerance and leukocytes within gWAT in the other models were unaffected compared to controls. Although IgG in gWAT was increased (+44 to +174%, P<0.05) in all mouse models lacking FcγRIIb, only FcγRI/II/III/IV/C3-/- mice exhibited appreciable alterations in immune cells in gWAT, for example, increased macrophages (+36%, P<0.001). CONCLUSIONS: Lack of FcγRs reduces the activity of macrophages upon IgG stimulation, but neither FcγR nor C3 deficiency protects against HFD-induced glucose intolerance or reduces adipose tissue inflammation. This indicates that if obesity-induced IgG contributes to the development of glucose intolerance, this is not mediated by FcγR or complement activation.

Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance, a Novel Antimicrobial Resistance Multilocus Typing Scheme for Tracking Global Dissemination of N. gonorrhoeae Strains.

A curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants in Neisseria gonorrhoeae was developed and is publicly accessible (https://ngstar.canada.ca). The N. gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (penA, mtrR, porB, ponA, gyrA, parC, and 23S rRNA) associated with resistance to ß-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entire penA sequence, combining the historical nomenclature for penA types I to XXXVIII with novel nucleotide sequence designations; the full mtrR sequence and a portion of its promoter region; portions of ponA, porB, gyrA, and parC; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (n = 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (n = 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval [CI] = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (n = 100; 13.0%), ST-42 and ST-91 (n = 45; 5.9%), ST-64 (n = 44; 5.72%), and ST-139 (n = 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (n = 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (n = 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (n = 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (n = 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistant N. gonorrhoeae strains.

The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis.

BACKGROUND: Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe. METHODS: We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy. RESULTS: Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches. CONCLUSIONS: The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.

A cross-sectional study to assess the long-term health status of patients with lower respiratory tract infections, including Q fever.

Patients with a lower respiratory tract infection (LRTI) might be at risk for long-term impaired health status. We assessed whether LRTI patients without Q fever are equally at risk for developing long-term symptoms compared to LRTI patients with Q fever. The study was a cross-sectional cohort design. Long-term health status information of 50 Q fever-positive and 32 Q fever-negative LRTI patients was obtained. Health status was measured by the Nijmegen Clinical Screening Instrument. The most severely affected subdomains of the Q fever-positive group were 'general quality of life' (40%) and 'fatigue' (40%). The most severely affected subdomains of the Q fever-negative group were 'fatigue' (64%) and 'subjective pulmonary symptoms' (35%). Health status did not differ significantly between Q fever-positive LRTI patients and Q fever-negative LRTI patients for all subdomains, except for 'subjective pulmonary symptoms' (P = 0·048).

Diagnosing lung cancer in the 21st century: are we ready to meet the challenge of individualized care?

BACKGROUND: Histologic and molecular subtyping have become increasingly important as predictors of treatment benefit in lung cancer. The objective of the present study was to determine whether current diagnostic approaches provide adequate tissue to allow for individualized treatment decisions. METHODS: Our retrospective cohort study of new lung cancer patients seen at an academic centre between July 2007 and June 2008 collected baseline demographic and diagnostic information, including mode of diagnosis, type of diagnostic material, and pathology diagnosis. RESULTS: Of the 431 study patients, 20% had stage i or ii non-small-cell lung cancer (nsclc), 24% stage iii disease, and 39% stage iv nsclc. Three quarters of the small-cell lung cancer (sclc) cases were extensive stage. Diagnostically, 18% of patients had sclc; 30%, adenocarcinoma; 27%, squamous-cell cancer; 2%, large-cell carcinoma; 1%, bronchoalveolar carcinoma; 1%, mixed histology; 18%, nsclc not otherwise specified; 4%, other; and 2%, no pathology diagnosis. Surgical pathology material was available in 80% of cases, and cytology material alone in 20%. Surgical pathology material was more common in patients with early-stage than with advanced disease (89% for stages i and ii vs. 74% for stages iii and iv, p < 0.0001). The pathology report included ambiguous terms in 24% of cases: "consistent" (12%), "suspicious" (3%), "favour" (2%), "suggestive" (2%), "likely" (1%), "compatible" with malignancy (1%), "at least" (1%), "atypical" (0.5%), and "no pathology" (1.5%). CONCLUSIONS: Current diagnostic approaches in most lung cancer patients appear adequate, but complete histopathologic identification is missing in nearly 20% of cases, and some uncertainty as to the final diagnosis is expressed in 24% of pathology reports. Some improvement in diagnostic sampling and pathology reporting are required to allow for implementation of current treatment approaches.

Borrelia burgdorferi sensu lato serology in the Netherlands: guidelines versus daily practice.

The purpose of this study was to compare guideline recommendations and day-to-day practice of serological testing for Lyme borreliosis (LB) in a laboratory located in Amsterdam, the Netherlands, serving both regional hospitals and primary care physicians. By telephone interview, we obtained clinical information regarding 488 requests for LB serology. Screening for LB was performed with a C6-peptide EIA and confirmed by recombinant immunoblot. A total of 82 % of the requests were not supported by guideline's recommendations and either originated from patients with atypical symptoms and a low a priori chance for LB or from patients for which testing on LB was not recommended for other reasons. C6-EIA screening was positive in 5 % of patients with atypical symptoms, comparable to the seroprevalence in the Dutch population. Interestingly, 10 % of the requests were from patients with atypical skin lesions, of which 20 % was positive, suggesting that serological testing is of additional value in a selection of such patients. Strikingly, only 9 % of the requests were supported by recommendations by guidelines. The percentage of positive confirmatory IgM and/or IgG immunoblots did not differ substantially between the groups and ranged from 56 to 75 %. Guidelines for testing for LB are not adequately followed in the Netherlands. Better education and adherence to the guidelines by physicians could prevent unnecessary diagnostics and antibiotic treatment of supposed LB patients.

[A monitor for the emergency psychiatric service chain]. / Een monitor voor de psychiatrische spoedzorgketen.

BACKGROUND: Many organisations are involved in the delivery of psychiatric emergency care to patients in crisis. We therefore refer to these organisations as the Psychiatric Emergency Chain (PEC). The quality of the PEC determines the quality of the psychiatric emergency care in a region. In order to measure the quality of this type of care a monitor has been developed in collaboration with the main stakeholders in the region Western North Brabant (WNB). AIM: To develop a monitor to measure the quality of a PEC in a region, identify weak spots in the chain and feed back the results to the chain. METHOD: By searching the literature, studying the primary process in the chain and by having interviews with stakeholders we compiled a questionnaire for monitoring the pec. The monitor was tested in the WNB region and adjusted on the basis of experiences with the respondents. Then the monitor was generalised and tested in another region (Eindhoven and the Kempen) in order to find out whether this instrument might also be applicable to other pecs in the Netherlands. RESULTS: The monitor provided the PEC with a common language for evaluating the chain. The monitor was able to pinpoint particular weak spots and collaboration problems such as the response time required to reach the emergency, communication between and within organisations and domain discussions between different stakeholders. Chain partners used the results of the monitor to negotiate better collaborative agreements and to improve their care. CONCLUSION: The monitor is able to pinpoint problem areas in the PEC and subsequently to generate feedback to its stakeholders. This creates opportunities for improvement in the PEC. Therefore the monitor is a useful instrument for evaluating a local PEC periodically.

[Somatic disorders in outpatient psychiatry: the added value of a standard physical examination during the intake of outpatients]. / Somatiek in de ambulante psychiatrie: de toegevoegde waarde van een standaard lichamelijk onderzoek tijdens de ambulante intake.

BACKGROUND: It is well-known that psychiatric patients often suffer from severe somatic problems, such as diabetes mellitus and cardiovascular disease. Up till now, research has concentrated almost exclusively on the inpatient setting, but there is strong evidence that the correlation also exists in psychiatric patients who are outpatients. In the Netherlands there are, as yet, no clear recommendations regarding a standard form of somatic screening for the outpatient population. A pilot study performed by GGz Breburg has shown that somatic screening (without a physical examination) gave substantial additional value to treatment planning. AIM: To investigate the added value that a physical examination can provide when new psychiatric patients are screened for aspects of somatic concern (ASC). METHOD: Newly referred outpatients (n = 70) were screened somatically by means of a questionnaire and supplementary medical interview, and by laboratory tests and physical examination. If a somatic problem was found which had not been detected previously, the patient was referred back to to the general practitioner. RESULTS: At least one ASC was found in 81,4% of all patients. In 45,7% of all patients the asc had not been detected. 12% of all the newly discovered somatic problems were found exclusively via the physical examination. CONCLUSION: A physical examination provides substantial information and adds value to the somatic screening of psychiatric outpatients.

Establishing an optimal working relationship with patients with an antisocial personality disorder. Aspects and processes in the therapeutic alliance.

OBJECTIVE: Developing good interpersonal relationships is one of the main impediments for people with an antisocial personality disorder (ASPD). However, in treatment of psychiatric disorders, establishing a strong therapeutic alliance (TA) is important for effective treatment. Nevertheless, there is little knowledge on how to establish this TA with this challenging patient group. This study investigates which factors are important in TA development. METHOD: For this study, a qualitative research methodology is applied. In-depth interviews with therapists experienced in treating ASPD were conducted and analysed through thematic analysis. RESULTS: The analysis revealed six themes important in alliance formation: the patient's needs, regulating interpersonal dynamics, connective attitude, connective skills, treatment process and treatment goals. Each theme is defined including aspects of the recommended therapeutic attitude and required skills for therapists working with patients with ASPD. CONCLUSIONS: This study determined that, for therapists working with patients with ASPD, several key factors are essential in establishing a strong TA. These factors include the ability to be firm, authentic, non-judgmental and genuinely involved. An attentive presence is crucial, in which the therapist takes initiative in establishing contact and makes the patient feel that he is truly seen as an autonomous and equal person. In doing so, the therapist needs to provide clarity and structure while remaining perceptive to boundary violations. The therapist must be able to set limits using a clear yet kind tone of voice. Furthermore, it was notable that an intensive appeal is made to the therapist's reflective capacity in these treatments.

Increased clonality among Neisseria gonorrhoeae isolates during the COVID-19 pandemic in Amsterdam, the Netherlands.

Distancing measures during the COVID-19 lockdown led to a temporary decrease of casual sex partners among clients of the Centre for Sexual Health (CSH) in Amsterdam, the Netherlands. We investigated the effect of this change on the genotypic and phenotypic distribution of Neisseria gonorrhoeae (Ng) isolates from CSH patients. From each Ng-positive patient we sequenced one isolate, resulting in 322 isolates which constituted two groups: 181 isolates cultured from 15 January to 29 February 2020 (before the first lockdown) and 141 cultured from 15 May to 30 June 2020 (during the first lockdown). Patient characteristics showed significantly more symptomatic patients and significantly fewer reported sex partners during the lockdown. Phenotypic data showed an increase in low-level azithromycin resistance and ceftriaxone susceptibility during the lockdown, and this remained after the study period. The diversity in sequence types (STs) decreased slightly during the lockdown. A shift occurred from ST 8156 being predominant before lockdown to ST 9362 during lockdown and a remarkably low median SNP distance of 17 SNPs was found between ST 9362 isolates obtained during lockdown. These findings reflect restricted travel and the change in sexual behaviour of CSH clients during the lockdown, with a potentially increased local transmission of the ST 9362 strain during this period, which led to genotypic and phenotypic changes in the Ng population. This shows that public health measures have far-reaching consequences and should be considered in the surveillance of other infectious diseases.

Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: a randomized controlled trial.

BACKGROUND: Cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) is an effective but intensive treatment, requiring trained therapists. A minimal intervention based on CBT for CFS, guided self-instruction, was shown to be an effective treatment when delivered in a tertiary treatment centre. Implementing this intervention in a community-based mental health centre (MHC) will increase the treatment capacity for CFS patients. This study evaluated the effectiveness of guided self-instruction for CFS implemented in an MHC, delivered by nurses. METHOD: One hundred and twenty-three patients were randomly assigned to either guided self-instruction (n=62) or a waiting list (n=61). Randomization was computer generated, with allocation by numbered sealed envelopes. Group allocation was open to all those involved. Patients fulfilled US Centers for Disease Control and Prevention (CDC) criteria for CFS. Primary outcome variables were fatigue severity and physical and social functioning, measured with the Checklist Individual Strength (CIS) and the Medical Outcomes Survey Short Form-36 (SF-36) respectively. RESULTS: After 6 months, patients who followed guided self-instruction reported a significantly larger decrease in fatigue compared to the waiting list [mean difference -8.1, 95% confidence interval (CI) -3.8 to -12.4, controlled effect size 0.70]. There was no significant difference in physical and social functioning. However, post-hoc analyses showed a significant decrease in fatigue and physical disabilities following the intervention in a subgroup of patients with physical disabilities at baseline (SF-36 physical functioning ⩽70). CONCLUSIONS: Implementation of guided self-instruction in a community-based MHC was partially successful. The minimal intervention can be effectively implemented for CFS patients with physical impairments.

Mass depopulation of laying hens in whole barns with liquid carbon dioxide: evaluation of welfare impact.

Appropriate emergency disaster preparedness is a key priority for agricultural agencies to allow effective response to serious avian disease outbreaks. There is a need to develop rapid, humane, and safe depopulation techniques for poultry that are widely applicable across a range of farm settings. Whole barn depopulation with carbon dioxide (CO(2)) has been investigated as a humane and efficient means of killing large numbers of birds in the event of a reportable disease outbreak. It has also been considered as a method for depopulating barns containing end-of-lay hens, particularly when there is limited local slaughter and rendering capacity. Determining the best method of humanely killing large flocks of birds remains problematic and is being investigated by a coordinated international effort. While whole barn depopulation using CO(2) inhalation has been explored, physiologic responses of chickens have not been characterized in field settings and assessment of animal welfare is hampered without this information. In this study, 12 cull laying hens were surgically instrumented with telemetry transmitters to record electroencephalographs, electrocardiographs, body temperature, and activity during 2 large-scale field CO(2) euthanasia trials of end-of-lay hens. The day following surgery, instrumented hens were placed in barns with other birds, barns were sealed, and animals were killed by CO(2) inhalation delivered via a specially designed liquid CO(2) manifold. Instrumented birds were monitored by infrared thermography, and ambient temperature, CO(2), and O(2) concentrations were recorded. Results from these studies indicate that instrumented hens lost consciousness within 2 min of CO(2) levels reaching 18 to 20%. Mild to moderate head shaking, gasping, and 1 to 2 clonic muscle contractions were noted in hens before unconsciousness; however, brain death followed rapidly (<5 min). Evaluation of welfare costs and benefits suggest clear advantages over catching and transporting cull hens for slaughter. The financial costs with this method are greater, however, than those estimated for traditional slaughter techniques. Results of these studies are being used to develop national protocols for whole barn depopulation of hens by CO(2) inhalation.

Treponema pallidum Subspecies Pallidum Intrapatient Homogeneity at Various Body Locations in Men with Infectious Syphilis.

Syphilis, caused by Treponema pallidum subspecies pallidum (TP), is a complex multistage infectious disease. Systematic dissemination occurs within a few hours of transmission. We determined the molecular variation of TP at various body locations and peripheral blood within patients in different stages of syphilis to assess the distribution of TP strains at these locations. We included 162 men who have sex with men (MSM) with syphilis visiting the Sexual Health Center in Amsterdam between 2018 to 2019, who had TP DNA detected in at least one sample type (anal swab, urine sample, peripheral blood, pharyngeal swab, and/or ulcer swab). TP DNA was detected in 287 samples using a qPCR targeting the polA gene. With multilocus sequence typing (TP-MLST) based on partial sequence analysis of three genetic regions (tp0136, tp0548, tp0705), we characterized all TP DNA positive samples. Samples could be typed (119/287) from at least one anatomical location or peripheral blood from 93/162 (57%) patients in the following stages: 48 (52%) primary, 35 (38%) secondary, and 10 (11%) early latent stage syphilis. The TP-MLST type was identical within each of the 12 patients with typed samples at ≥2 different body locations. The most prevalent TP strains were 1.3.1 (39/93, 42%) and 1.1.1 (17/93, 18%) belonging to the SS14 lineage; 80% (74/93) of the patients carried a SS14 lineage TP strain and 20% (19/93) Nichols lineage. The distribution of TP-MLST types did not differ between patients by syphilis stage. We found intrapatient TP strain homogeneity and no TP strain variation between anatomical location or syphilis stages. More early latent samples should be typed and added in future studies to investigate this in more detail. IMPORTANCE Syphilis, caused by Treponema pallidum subspecies pallidum, is a complex multistage infectious disease. Systematic dissemination is known to occur within a few hours of transmission. Despite the effective antibiotic penicillin, syphilis remains prevalent worldwide. Men who have sex with men are disproportionally affected in high income countries like the Netherlands where 96% of the syphilis cases in 2020 were among this population. The inability to in vitro culture T. pallidum directly from patient samples limits whole-genome sequencing efforts. Fortunately, in 2018 a multilocus sequence typing technique was developed for T. pallidum allowing the monitoring of circulating strains. The significance of our research is in the investigation of T. pallidum molecular variation at various body locations and blood within patients in different stages of syphilis in order to assess the distribution of strains at these locations.