A mixed-methods evaluation of hepatitis B knowledge, attitudes, and practices among migrant women in Thailand.

BACKGROUND: Globally 90 % of transmission of Hepatitis B virus (HBV) is from mother-to child and occurs predominantly in resource limited countries where the prevalence of HBV is high. Transmission could be interrupted by timely vaccinations but coverage remains problematic in these areas. Low knowledge or awareness of HBV may play a part in low vaccination coverage. This study examines the provision of antenatal care counselling with a focus on HBV in two different regions of northern Thailand, Sarapee Hospital (SH), Chiang Mai, and Shoklo Malaria Research Unit (SMRU), Tak Province. METHODS: A mixed-methods sequential explanatory study design was used to evaluate antenatal services for migrants. Cross-sectional knowledge, attitude and practice (KAP) surveys were conducted immediately after counselling at first ANC contact, at 3-6 months after first ANC contact and at delivery. Surveys provided quantitative data, and qualitative methods included observations, focus group discussions (FGD) and in-depth interviews (IDI); analysed thematically to explore concepts of knowledge and understanding, attitude and practice of pregnant women and providers. RESULTS: Between September-2019 and May-2020, 757 women participated to KAP surveys, and 31 observations of counselling, 16 FGD and 9 IDI were conducted. KAP surveys showed in spite of low knowledge about HBV transmission, infection, or vaccination (correct response: SH 5.7 %, 9/157; SMRU 34.0 %, 204/600), most women (≥ 93 %, either site) understood they were screened for HBV and were willing to vaccinate infants for HBV. In explaining KAP survey results, qualitative analysis suggests counselling should: use the appropriate language; be tailored to the local health literacy level, provide only pertinent information, be repeated over the antenatal period; and attempt to ensure patient privacy (where possible). Programme effectiveness benefits from positive attitudes to screening and vaccinations and a high level of trust in the providers nevertheless participants provided good suggestions for improvements of the service. CONCLUSIONS: Limited knowledge of HBV among migrant women can be improved by counselling that emphasizes actionable knowledge such as vaccination schedule. Key improvements to the counselling process include training counsellors to conduct interactive counselling sessions in the woman's language, using appropriate visual aids and timely repetition over the course of the antenatal period.

[Assertive Treatment as a regular function within mental health]. / Van bemoeizorg naar assertieve behandeling als regulier aanbod vanuit de ggz.

BACKGROUND: The setting for providing assertive treatment (AT) has changed during the last 30 years in The Netherlands from assertive community treatment (ACT) and flexible assertive community treatment (FACT) to municipalities. The provision of AT varies between municipalities. AIM: Describing the concept of AT, the nature and size of the target group, and the reasons why people with severe mental illness (SMI) do not seek treatment and the place of AT in mental health care. METHOD: We used literature en available quantitative data. RESULTS: AT regularly provided by mental health care is required in patients with SMI and social problems who do not seek treatment. When mental health care and social care collaborate on the level of the patient, treatment and handling of social problems can strengthen each other. This collaboration prevents discontinuity of care and breaking a trusting relationship because patients do not need to be transferred from social service to mental health care or vice versa. AT is on the continuum of voluntarily to compulsory care.AT provided by mental health care (usually provided by FACT-teams) is indicated for SMI patients with social problems and who do not seek treatment. The size of the target group is around 5000 - 20.000 patients in The Netherlands. Reasons not to seek help for people with SMI include within person factor, mental health related factors, or factors related to the interaction of SMI patients and mental health. We advocate for AT to become a regular part of mental health care, and for mental health care and social domain professionals to collaborate on case level. Acting this way, mental health treatment and addressing social problems can reinforce each other and discontinuity of care and breaking a trusting relationship can be prevented. AT is on the continuum of voluntary to involuntary treatment. That is why we suggest AT to be a better term than assertive outreach. CONCLUSION: It is a given fact that not all patients with SMI and social problems seek treatment. By making AT a regular part of mental health services, we prevent discontinuity of care and we fill the gap between voluntarily and compulsory care.

Tenofovir for prevention of mother to child transmission of hepatitis B in migrant women in a resource-limited setting on the Thailand-Myanmar border: a commentary on challenges of implementation.

BACKGROUND: The aim of this manuscript is to highlight challenges in the implementation of maternal tenofovir disoproxil fumarate (tenofovir) for prevention of mother to child transmission (PMTCT) of hepatitis B virus (HBV) in resource limited setting. Current preventive strategies in resource-limited settings fail mainly due to prohibitive costs of hepatitis B immunoglobulin (HBIG) and a high proportion of homebirths, meaning both HBIG and hepatitis B birth dose vaccine are not given. A new strategy for PMTCT without the necessity of HBIG, could be daily tenofovir commenced early in gestation. Implementation challenges to early tenofovir for PMTCT can provide insight to elimination strategies of HBV as the burden of disease is high in resource-limited settings. METHODS: Challenges encountered during implementation of a study of tenofovir for PMTCT before 20 weeks gestation in rural and resource-limited areas on the Thailand-Myanmar border were identified informally from trial study logbooks and formally from comments from patients and staff at monthly visits. ClinicalTrials.gov Identifier: NCT02995005. MAIN BODY: During implementation 171 pregnant women were hepatitis B surface antigen (HBsAg) positive by point of-care test over 19 months (May-2018 until Dec-2019). In this resource-limited setting where historically no clinic has provided tenofovir for PMTCT of HBV, information provided by staff resulted in a high uptake of study screening (95.5% (84/88) when offered to pregnant women. False positive point-of-care rapid tests hinder a test and treat policy for HBV and development of improved rapid tests that include HBeAg and/or HBV DNA would increase efficiency. Integrated care of HBV to antenatal care, transport assistance and local agreements to facilitate access, could increase healthcare at this critical stage of the life course. As safe storage of medication in households in resource-limited setting may not be ideal, interactive counseling about this must be a routine part of care. CONCLUSION: Despite challenges, results from the study to date suggest tenofovir can be offered to HBV-infected women in resource-limited settings before 20 weeks gestation with a high uptake of screening, high drug accountability and follow-up, with provision of transportation support. This commentary has highlighted practical implementation issues with suggestions for strategies that support the objective of PMTCT and the World Health Organization goal of HBV elimination by 2030.

[Flexible assertive community treatment (FACT) as part of a community (health) network]. / FACT als onderdeel van wijkgerichte zorg in het (zorg)netwerk.

BACKGROUND: Community-based care for people with severe mental illness increasingly requires far-reaching cooperation between different domains. This cooperation must always be unique and local, and at the same time provide an answer to generic and nationally set goals.
AIM: Offering new insights on collaboration within and between domains.
METHOD: Reflection on developments in the social domain and specialist mental healthcare using relevant literature and recent (inter)national experiences.
RESULTS: It seems possible to provide better integral care by allowing FACT-teams to network together with Social Support partners (e.g. by sharing financial and/or human resources). In this process, networks of care for people with serious mental illness (SMI), develop over various phases and realize new partnerships. The model fidelity scale for FACT-teams was adjusted to facilitate that process. CONCLUSIONS The new FACT model fidelity scale is ready to allow FACT-teams to explore flexible local solutions for partnerships to realize the much-needed multi-domain integrated community care for people with SMI.

[Development of the renewed Flexible ACT scale: F-ACT fidelity 2017]. / De ontwikkeling van de vernieuwde Flexible ACT-schaal: F-ACT-s 2017.

BACKGROUND: An important model for the organisation of care for people with severe mental illness is flexible assertive community treatment (F-ACT). F-ACT combines case management with assertive crisis intervention. Quality control was implemented in 2008 using a model fidelity scale. Research has shown that the norms used for the F-ACT fidelity scale no longer correspond with current norms concerning restorative and evidence-based care, as established in treatment guidelines.
AIM: To develop a new model fidelity scale for F-ACT teams.
METHOD: Using knowledge of experts, relevant articles and feedback from professionals, researchers, interest groups and family members, a new model fidelity scale was developed: the F-ACTs 2017. The revised scale was tested by trained auditors in 21 F-ACT teams and adjusted in two pilot rounds.
RESULTS: In 2017 the final version was presented to the stakeholders and was approved by the board of auditors; the final version is currently in use. CONCLUSIONS With the availability of F-ACTs 2017, the (research) field has state-of-the-art instrument to monitor the quality of care of persons with severe mental illness. It uses field standards to evaluate the degree of model fidelity of teams that focus on patients with severe mental illness in a rapidly changing context.

[Model fidelity of flexible assertive community treatment (F-ACT) teams: five years of audit results]. / Modelgetrouwheid van flexible assertive community treatment(F-ACT)-teams: resultaten van vijf jaar auditeren.

BACKGROUND: The Flexible act (f-act) has been introduced in the Netherlands since 2004, alongside the Assertive Community Treatment (act) model. An estimate of 400 (f-)act teams concurrently provide care to approximately 70.000 people with serious mental illness. The ccaf has been assessing the model fidelity of act and f-act teams since 2009 to promote the quality and transparency of healthcare for clients with serious mental illness. OBJECTIVE To describe the state of implementation of f-act and associated trends in the Netherlands.
METHOD: Analysis of the ccaf database, which holds the data of audits conducted between 2009 and 2014.
RESULTS: The audits conducted by ccaf between 2009 and 2014 indicated an adequate implementation of f-act. The team foundations were well organized, featuring a multidisciplinary team structure, management of medication, practical support and investment in healthcare continuity, including during an admission. However, the results regarding participation and recovery were unsatisfactory. Furthermore, the results depicted a decline in the scores concerning a number of areas, including outreach and support of participation and recovery. CONCLUSIONS Although the data indicates an on average satisfactory implementation of f-act in the Netherlands, there are signs that the implementation of f-act is under pressure with relatively fewer home visits, a rising caseload and a reduced investment in recovery and participation. The findings are in accordance with the signs and arguments to adjust the emphasis on reducing hospital admissions, prioritizing the consolidation of outpatient care instead.

Low incidence of the immune reconstitution inflammatory syndrome among HIV-infected patients starting antiretroviral therapy in Gabon: a prospective cohort study.

There is a paucity of data on the immune reconstitution inflammatory syndrome (IRIS) in the Central African region. We followed ART-naive HIV-infected patients initiating antiretroviral therapy in an HIV clinic in Gabon, for 6 months. Among 101 patients, IRIS was diagnosed in five. All IRIS cases were mucocutaneous manifestations. There were no cases of tuberculosis (TB) IRIS, but active TB (n = 20) was associated with developing other forms of IRIS (p = 0.02). Six patients died. The incidence of IRIS is low in Gabon, with mild, mucocutaneous manifestations.

[Forensic (flexible) assertive community treatment: client characteristics and treatment outcomes]. / Forensische (flexibele) assertive community treatment ((F)ACT): cliëntkenmerken en behandelresultaten.

BACKGROUND: (Flexible) Assertive community treatment ((f)act) is applied increasingly to forensic psychiatric clients. However, evidence about the effectiveness of forensic (f)act is scanty. AIM: To investigate to what extent (subgroups of) clients receiving care from forensic (f)act teams show, after a year, changes in their social and psychological functioning and are subjected to fewer justicial outcome measures. METHOD: Between 2009 and 2011, eight forensic (f)act teams collected, at two measurement moments separated by an average of 12 months, data relating to client characteristics and outcomes of care. The study involved 202 clients. RESULTS: After a year clients showed significant improvements in psychological and social functioning, and had fewer confrontations with the police and the law. They were detained less often and for shorter periods and were considered to be less likely to reoffend. The number of admissions to mental health care and to addiction and forensic care remained constant. CONCLUSION: Clients with a psychiatric disorder and likely to display criminal behaviour showed improvement while being treated by forensic (f)act teams. Further research is needed to prove whether forensic (f)act treatment will have the desired effects in the longer term and will enjoy the status of being regarded as evidence based practice.

Eosinophilia à deux: a brain nagging souvenir from the Philippines.

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis. Although a rare condition among travelers, increased travel and global transportation of food products may result in more cases across non-endemic, developed countries in the future. We here describe two men with headache and painful skin after visiting the Philippines as presenting symptoms. Subsequently, confusion and focal neurologic symptoms developed. Both had increased serum eosinophils; however, CSF eosinophilia was only demonstrated after repeated lumbar puncture. In the CSF of both, Angiostrongylus spp. DNA was detected. Both were treated with albendazole combined with corticosteroids, after which symptoms improved.

Immunization after renal transplantation: current clinical practice.

BACKGROUND: The use of potent immunosuppressive drugs and increased travel by renal transplant recipients (RTR) has augmented the risk for infectious complications. Immunizations and changes in lifestyle are protective. The Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group has developed guidelines on vaccination following solid organ transplantation. The degree of adherence to these guidelines is unknown, as is which barriers must be overcome to improve adherence. METHODS: We performed a cross-sectional national survey among Dutch nephrologists to assess vaccination policy and adherence to the KDIGO guidelines. In addition, to investigate awareness and attitude of RTR regarding their risk of infection, we performed a cross-sectional survey of RTR in our outpatient clinic. RESULTS: A total of 132 (63%) nephrologists completed the survey. Reported immunization rates were 90.8% for influenza and 27.3% for hepatitis B. However, pneumococcal, tetanus toxoid, and meningococcal immunization rates were low. Twenty-seven percent of respondents were familiar with the guideline contents. The most frequent perceived barrier to guideline adherence was expectation of low effectiveness. A total of 403 RTR (62%) completed the survey. Sixty-eight percent perceived more risk for complicated infection. A significant correlation was found between education level and variables concerning awareness and attitude toward risk of infection. CONCLUSIONS: Our results show that nephrologists' knowledge of and adherence to the recommendations regarding immunization after renal transplantation is suboptimal. Most Dutch RTR are aware of their increased risk and the possible seriousness of infectious complications. However, their behavior does not match their awareness. This disparity points to an important role for nephrologists in providing adequate counseling.

Checkpoint kinase 2 (Chk2) supports sensitivity to platinum-based treatment in high grade serous ovarian cancer.

OBJECTIVE: Platinum-based chemotherapy is the standard treatment in advanced stage high grade serous ovarian cancer (HGSOC), but the majority of patients will relapse with drug-resistant disease. Platinum induces double-strand DNA breaks and subsequently activation of the DNA damage response (DDR). Drugs targeting DDR pathway components have gained major interest to be combined with chemotherapy as they could increase the therapeutic window. In the present study, we investigated the activation status of the Ataxia Telangiectasia Mutated (ATM) signaling axis within the DDR in a large, well-defined cohort of advanced stage HGSOC patients. METHODS: Pre-therapy activation status of the ATM signaling axis of the DDR was determined by immunohistochemistry in 125 chemo-naive advanced stage HGSOC patients. Ovarian cancer cell lines with stable checkpoint kinase 2 (Chk2) knock down were used to study cell cycle distribution and survival in long-term clonogenic survival assays. RESULTS: All ATM signaling axis components showed high expression levels. In two well-defined groups with the largest contrast in treatment response, high expression of Chk2 was related to good response (OR=0.132; P=0.014). Chk2 depletion abrogated the cisplatin-induced S-phase cell cycle arrest and caused increased resistance to cisplatin in long-term clonogenic survival assays. CONCLUSIONS: Chk2 is related to good response to platinum-based chemotherapy in advanced stage HGSOC patients. Chk2-depleted ovarian cancer cell lines have diminished platinum sensitivity, suggesting that Chk2 should not be considered a therapeutic target along with platinum-based treatment in HGSOC patients.

TB and HIV in the Central African region: current knowledge and knowledge gaps.

PURPOSE: Reliable and comprehensive data on the HIV/AIDS and TB co-pandemics from Central Africa remain scarce. This systematic review provides a comprehensive overview on current and past research activities in the region and provides a basis for future research work to close knowledge gaps. METHODS: The scientific literature was searched for publications meeting the following search terms: "tuberculosis" or "HIV" or "acquired immunodeficiency syndrome", combined with "Central Africa", or the names of individual countries within the region. Original studies, reviews and case series were included, and a selection of relevant articles was made. RESULTS: Most research in the field of HIV and TB has been conducted in Cameroon, where the epidemics have been described fairly well. The Democratic Republic of Congo ranked second on the amount of publications, despite the civil wars over the past several decades. Very little has been published on HIV and TB in the other countries, possibly due to the poor infrastructure of health care systems, lack of scientific capacity building or shortage of laboratory equipment. CONCLUSIONS: Despite the relatively high burden of HIV and TB in the Central African region, the amount of research activities on these topics is limited. A better understanding of the co-epidemics in this region is urgently needed. The occurrence of opportunistic infections, treatment complications and drug resistance in TB and HIV need to be better described; the failure of public health systems needs to be understood, and research infrastructure needs to be developed. Only then will it be possible to turn the tide against the HIV and TB epidemics in this region.

Rabies vaccinations: are abbreviated intradermal schedules the future?

Rabies is a deadly disease, and current preexposure vaccination schedules are lengthy and expensive. We identified nine studies investigating abbreviated schedules. Although initial responses were lower, accelerated adequate immune responses were elicited after booster vaccinations. Lower-dose (and therefore cheaper) vaccination schedules may constitute a valid alternative to current vaccination schedules.

Unravelling mechanisms of cisplatin sensitivity and resistance in testicular cancer.

Testicular cancer is the most frequent solid malignant tumour type in men 20-40 years of age. At the time of diagnosis up to 50% of the patients suffer from metastatic disease. In contrast to most other metastatic solid tumours, the majority of metastatic testicular cancer patients can be cured with highly effective cisplatin-based chemotherapy. This review aims to summarise the current knowledge on response to chemotherapy and the biological basis of cisplatin-induced apoptosis in testicular cancer. The frequent presence of wild-type TP53 and the low levels of p53 in complex with the p53 negative feed-back regulator MDM2 contribute to cisplatin sensitivity. Moreover, the high levels of the pluripotency regulator Oct4 and as a consequence of Oct4 expression high levels of miR-17/106b seed family and pro-apoptotic Noxa and the low levels of cytoplasmic p21 (WAF1/Cip1) appear to be causative for the exquisite sensitivity to cisplatin-based therapy of testicular cancer. However, resistance of testicular cancer to cisplatin-based therapy does occur and can be mediated through aberrant levels of the above mentioned key players. Drugs targeting these key players showed, at least pre-clinically, a sensitising effect to cisplatin treatment. Further clinical development of such treatment strategies will lead to new treatment options for platinum-resistant testicular cancers.

p38 inhibition and not MK2 inhibition enhances the secretion of chemokines from TNF-α activated rheumatoid arthritis fibroblast-like synoviocytes.

OBJECTIVES: For many years the p38 MAP kinase (MAPK) has been a major anti-inflammatory target for the development of an oral therapy for rheumatoid arthritis (RA). However, disappointing results from Phase II clinical studies suggest that adaptations may occur, which allow escape from blockade of the p38 pathway. In this study we investigated whether p38 inhibition mediated JNK activation represents such an escape mechanism. METHODS: Interaction between the JNK and p38 pathways was studied in TNF-α stimulated THP-1 monocytes, primary macrophages and fibroblast-like synoviocytes from OA and RA patients using pharmacological inhibitors and siRNAs. RESULTS: TNF-α induced phosphorylation of JNK and c-Jun was sustained by p38 inhibitors in monocytes, primary macrophages and FLS. Upregulation of Mip1α, Mip1ß and IL-8 mRNAs and protein were observed upon p38 inhibition. More importantly, inhibition of MK2, the substrate of p38 did not sustain JNK activation upon TNF-α activation and did not elevate Mip1α, Mip1ß and IL-8 chemokines as compared to TNF-α alone. In this study, TNF-α or IL-1ß induced JNK activation is sustained by p38 inhibition, resulting in enhanced chemokine secretion. CONCLUSIONS: Based on the suggested role of these chemokines in RA pathogenesis, the upregulation of these chemokines may provide an explanation for the lack of efficacy of p38 inhibitors in Phase II. The absence of any effect of MK2 inhibition in our models on this mechanism, while coming with similar efficacy on blocking p38, provides support for further investigations to reveal the potential of MK2 inhibition as a novel treatment of RA.

A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study.

BACKGROUND: In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer. PATIENTS AND METHODS: In a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS). RESULTS: 151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients. CONCLUSION: Celecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.

A shifting paradigm? A scoping review of the factors influencing recovery and rehabilitation in recent forensic research.

Forensic research and practice have historically focused on risk assessment and prevention. This risk-oriented paradigm is shifting towards a more recovery-oriented perspective. The aim of this scoping review is to provide an overview of research on the factors influencing rehabilitation and recovery and discuss the recovery paradigm in a forensic setting. We performed a systematic search of the literature from the past 10 years, in Pubmed, Cinahl and PsycInfo, on recovery and rehabilitation. All types of study designs were included. Data was analysed and charted using an Excel template with various data items of interest. Clinical, personal, social, functional and forensic factors were found to be of influence on recovery and rehabilitation. A number of these overlapped with factors of influence on recidivism and desistance, others did not. Most studies on recovery and rehabilitation focused on a clinical forensic setting. This study provides an overview of the current body of knowledge on the factors influencing recovery and rehabilitation in forensic clients, and encourages researchers and practitioners in their focus on the recovery paradigm in forensic care. The body of evidence on rehabilitation and recovery is not yet as profound as that on recidivism and desistance. More knowledge on recovery trajectories for offenders in prison or ambulatory care, for example, is required.

[Development of a fidelity scale for function assertive community treatment (FACT)]. / Ontwikkeling van een modelgetrouwheidsschaal voor functie-assertive community treatment (FACT).

BACKGROUND: Assertive community treatment (ACT) is one of the most important models for the care and treatment, in the community, of people with severe mental illness (SMI). ACT is concerned primarily with smi-patients who have the most complex problems and it provides care by means of intensive assertive outreach. Function act (FACT) provides care for the entire group of SMI - patients and combines the principles of case management and ACT. For a long time it has been possible to measure the degree of ACT model reliability using the facts reliability scale. Throughout this time, however, a reliability scale for FACT was not available. AIM: To develop a reliability scale for fact teams. METHOD: Using the knowledge of experts and feedback from fact teams it has been possible to develop a reliability scale for fact teams. The scale was tested and subsequently adapted as a result of 10 pilot trials performed by 10 fact teams. RESULTS: The definitive version of the scale was confirmed in 2008 and is currently used in the field. CONCLUSION: With the ACT and FACT reliability scales the research field now have two instruments with which teams working with SMI - patients can measure model reliability. The DACTS and FACTS provide opportunities for quality improvement and transparency.

A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2. METHOD: The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2. DISCUSSION: This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms. TRIAL REGISTRATION: Netherlands Trial Register NL8947 . Registered on 14 October 2020.

Miltefosine treatment of Leishmania major infection: an observational study involving Dutch military personnel returning from northern Afghanistan.

In a retrospective, observational study involving 34 patients with Leishmania major infection, 31 of whom had experienced unsuccessful treatment with intralesional antimony (ilSb(v)), miltefosine proved effective. Thirty patients experienced cure after receipt of miltefosine, 3 after receipt of additional ilSb(v), and 1 after 28 daily intravenous injections of antimony. Temporary diminution of ejaculate volume was reported by 21 patients.