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As one article in a series on Global Mental Health Practice, Peter Ventevogel and colleagues provide a case study of their efforts to integrate brief, practice-oriented mental health training into the Afghanistan health care system at a time when the system was being rebuilt from scratch. [ABSTRACT FROM AUTHOR]

Frameworks conceptualising the quality of care abound and vary; some concentrate on specific aspects such as safety, effectiveness, others all-encompassing. However, to our knowledge, tailoring to systematically arrive at a comprehensive care for chronic conditions quality (CCCQ) framework has never been done. We conducted a scoping review and Delphi survey to produce a CCCQ framework, comprehensively delineating aims, determinants and measurable attributes. With the assumption that specific groups (people with chronic conditions, care providers, financiers, policy-makers, etc.) view quality of care differently, we analysed 48 scientific and 26 grey literature deductively and inductively using the Institute of Medicine's quality of care framework as the foundation. We produced a zero-version of the quality of chronic care framework, detailing aims, healthcare system determinants, and measurement mechanisms. This was presented in a Delphi survey to 49 experts with diverse chronic care expertise/experience around the world. Consensus was obtained after the first round, with the panel providing suggestions and justifications to expand the agreed-upon components. Through this exercise, a comprehensive CCCQ framework encompassing the journey through healthcare of people with chronic conditions was developed. The framework specifies seven CCCQ 'aims' and identifies health system determinants which can be acted upon with 'organising principles' and measured through chronic care quality 'attributes' related to structures, processes and outcomes. Tailoring quality of care based on the nature of the diseases/conditions and considering different views can be done to ensure a comprehensive offer of healthcare services, and towards better outcomes that are acceptable to both the health system and people with chronic conditions (PwCC).

There is a growing need to implement high quality chronic care to address the global burden of chronic conditions. However, to our knowledge, there have been no systematic attempts to define and specify aims for chronic care quality. To address this gap, we conducted a scoping review and Delphi survey to establish and validate comprehensive specifications. The Institute of Medicine's (IOM) quality of care definition and aims were used as the foundation. We purposively selected articles from the scientific (n=48) and grey literature (n=26). We sought papers that acknowledged and unpacked the plurality of quality in chronic care and proposed or utilised frameworks, studied their implementation, or investigated at least two IOM quality care aims and implementation. Articles were analysed both deductively and inductively. The findings were validated through a Delphi survey involving 49 international chronic care experts with varied knowledge of, and experience in, low-and-middle-income countries. Considering the natural history of chronic conditions and the journey of a person with a chronic condition, we defined and identified the aims of chronic care quality. The six IOM aims apply with specific meanings. We identified a seventh aim, continuity, which relates to the issue of chronicity. The group endorsed our specifications and several participants gave contextualised interpretations and concrete examples. Chronic conditions pose specific challenges underscoring the relevance of tailoring quality of care aims. The next steps require a tailored definition and specific aims to improve, measure and assure the quality of chronic care.

Background: Patients with facioscapulohumeral dystrophy (FSHD) suffer from slowly progressive muscle weakness. Approximately 20% of FSHD patients end up wheelchair-dependent. FSHD patients benefit from physical activity to maintain their muscle strength as much as possible. The impact of the COVID-19 pandemic on the health of FSHD patients was unknown., Objective: This study assessed changes in daily care received, perceived psychosocial stress, and worsening of FSHD complaints in 2020. Furthermore, we compared COVID-19 infection incidence and severity of symptoms between FSHD patients and non-FSHD housemates., Methods: Three online survey rounds were sent out to all adult participants of the Dutch FSHD registry regarding daily care received, perceived psychosocial stress, COVID-19 infection rate, and COVID-19 symptoms severity. They also included COVID-19-related questions regarding the participants' housemates, which served as control group., Results: Participation rate was 210 (61%), 186 (54%), and 205 (59%) for survey 1, 2, and 3, respectively. Care reduction was reported by 42.7%, 40%, and 28.8% of the participants in the respective surveys. Perceived psychosocial stress increased in 44%, 30%, and 40% of the participants. Compared to the 197 non-FSHD housemates, the 213 FSHD patients reported more possibly COVID-19-related symptoms (27% vs. 39%, p = 0.017) of mostly minimal severity (63%). No difference in (possible) COVID-19 infection incidence rates was found (2.0% vs. 2.8%, p = 0.527)., Conclusions: The COVID-19 pandemic negatively impacted care received and increased perceived psychosocial stress in FSHD patients. However, COVID-19 infection incidence in FSHD patients was similar to their non-FSHD housemates., (© 2024. The Author(s).)

Introduction: The COVID-19 pandemic has exacerbated an already existing security crisis leading to massive population displacements that have been taking place since 2012., Purpose of Research: This study aims to explore the representations of internally displaced persons (IDPs) about the existence of COVID-19 and their knowledge about its signs, symptoms, modes of transmission and prevention measures., Methods: The study was qualitative and exploratory. Individual and group interviews were used to collect data from 52 IDPs in six sites in Bamako and Segou. All interviews were recorded and transcribed. Thematic content analysis and N-Vivo software were used., Results: The majority of IDPs believed in the existence of COVID-19 and had good knowledge of the signs, symptoms, modes of transmission and prevention measures against the disease. However, this was not sufficient for the adoption of public health measures. Among those who believed in its existence, some thought that it was a disease of the white and rich. Finally, a group of participants believed in conspiracy theories and claimed that the government and humanitarian organizations were only trying to make money through these campaigns., Conclusion: To our knowledge, this is the first study in Mali to explore IDPs’ beliefs and knowledge about COVID-19. These results could inform policies, strategies, and interventions to combat COVID-19 in IDP sites and in the general population.

Background: Telemedicine enables new forms of medical consultation and is expanding worldwide. Patients in sub-Saharan Africa could potentially benefit substantially from telemedicine., Objective: To improve primary healthcare services, especially referrals to the district hospital, for the population in three health centres in the rural district Kingandu in the Democratic Republic of the Congo (DRC) by introducing Smart Glasses, and leveraging them for telemedicine., Methods: The project involved the design and introduction of an intervention combining community engagement with technological innovation (Smart Glasses, communication equipment, moto-ambulances, and new diagnostic tests), and with staff training. Utilisation of the intervention, use of the health centres, and referrals to the hospital were monitored through the routine health information system and project-specific registers. Key stakeholders were interviewed and the project costs were analysed., Results: The use cases for the intervention were defined in consultation with the stakeholders. Smart Glasses were used in 10% of consultations in the health centres mostly for advice during curative consultations. The total number of consultations increased significantly in the intervention health centres. The number of referrals to the hospital remained stable, but an increased proportion effectively arrived in the hospital. The Smart Glasses and moto-ambulance greatly facilitated emergency referrals, often requiring a potentially life-saving intervention in the hospital. All stakeholders involved highly valued the intervention., Conclusion: Telemedicine can contribute to improving primary healthcare services in a remote rural area, as part of a more comprehensive intervention and with intensive participation of all stakeholders. It can increase acceptability and use of the existing services; improve diagnosis, treatment, and referral of patients; and can also facilitate on-the-job training and supportive supervision.

Objective: The study aims to document the experience of integrating a mental health care package into the general health care system of Lubero district in the Democratic Republic of Congo (DRC) between 2011 and 2015, and more specifically, the effects of this integration on the access to and use of health services offering mental health care., Method: This is a retrospective study using a case study design. Data collected from different project documents and an analytic review of the official reports of the Ministry of Public Health were used for an analysis of the results of the integration., Results: The results indicate that 3,941 patients with mental health problems used the care offered at the health centers and the district hospital between 2012 and 2015. In 2015, the average utilization rate of curative care in health centers for mental health problems was 7 new cases/1,000 inhabitants/year. The majority of these patients were treated on an outpatient basis, at primary health care level., Discussion: Our study shows that it is possible to integrate mental health into existing general health services in the DRC. Nevertheless, the major problems in terms of access and use of basic care in the Lubero district indicate that the success of such an integration depends on the quality of the health system in place and the involvement of a wide range of both health and non-health actors, including key people within communities.

Background: Guinea undertook health workforce reform in 2016 following the Ebola outbreak to overcome decades-long shortages and maldistribution of healthcare workers (HCWs). Specifically, over 5000 HCWs were recruited and deployed to rural health districts and with a signed 5-year commitment for rural medical practice. Governance structures were also established to improve the supervision of these HCWs. This study assessed the effects of this programme on local health systems and its influence on HCWs turnover in rural Guinea., Methods: An exploratory study design using a mixed-method approach was conducted in five rural health districts. Data were collected through semi-structured questionnaires, in-depth interview guides, and documentary reviews., Results: Of the 611 HCWs officially deployed to the selected districts, 600 (98%) took up duties. Female HCWs (64%), assistant nurses (39%), nurses (26%), and medical doctors (20%) represented the majority. Findings showed that 69% of HCWs were posted in health centres and the remaining in district hospitals and the health office (directorate); the majority of which were medical doctors, nurses, and midwives. The deployment has reportedly enhanced quality and timely data reporting. However, challenges were faced by local health authorities in the posting of HCWs including the unfamiliarity of some with primary healthcare delivery, collaboration conflicts between HCWs, and high feminization of the recruitment. One year after their deployment, 31% of the HCWs were absent from their posts. This included 59% nurses, 29% medical doctors, and 11% midwives. The main reasons for absenteeism were unknown (51%), continuing training (12%), illness (10%), and maternity leave (9%). Findings showed a confusion of roles and responsibilities between national and local actors in the management of HCWs, which was accentuated by a lack of policy documents., Conclusion: The post-Ebola healthcare workers policy appears to have been successfully positive in the redistribution of HCWs, quality improvement of staffing levels in peripheral healthcare facilities, and enhancement of district health office capacities. However, greater attention should be given to the development of policy guidance documents with the full participation of all actors and a clear distinction of their roles and responsibilities for improved implementation and efficacy of this programme.

In Brussels, many migrant women without legal status have no or limited access to health care and other basic services. Their access to descent care is mainly hampered by a lack of information, limited financial resources and poor experiences in the past. Three non-governmental organisations joint efforts to help migrant women without legal status to come out of their isolation. Action research during the implementation process was conducted in order to know which elements contributed to increased feelings of trust and reinforced autonomy among the target group and more willingness to support migrants among a larger population. Our major conclusion is that mental health and well-being is largely defined by (the quality of) social relations and interactions - an aspect that is too often forgotten as a result of the medicalization of mental health related problems.

During inflammatory reactions, endogenously produced cytokines and chemokines act in a network and interact with hormones and neurotransmitters to regulate host immune responses. These signaling circuitries are even more interfaced during infections, when microbial agonists activate TLR, RLR, and NLR receptors. On the basis of the discovery of synergy between chemokines for neutrophil attraction, we extend here this phenomenon between the chemokine MCP-1/CCL2 and the GPCR ligand fMLP or the TLR4 agonist LPS on monocytes. In fact, the bacterial tripeptide fMLP, but not the cytokines IL-1beta or IFN-gamma, significantly and dose-dependently synergized with CCL2 in monocyte chemotaxis. Furthermore, LPS rapidly induced the expression of IL-8/CXCL8 but not of the CCL2 receptor CCR2 in monocytic cells. In turn, the induced CXCL8 synergized with CCL2 for mononuclear cell chemotaxis, and the chemotactic effect was mediated by CXCR1/CXCR2, because CXCL8 receptor antagonists or antibodies were capable of blocking the synergy, while keeping the responsiveness to CCL2 intact. These data recapitulate in vitro the complexity of innate immune regulation, provide a novel mechanism of enhancing monocyte chemotaxis during bacterial infections with gram-negative bacteria and demonstrate the importance of local contexts in inflammatory and infectious insults.

Chemokines are important in inflammation and in carcinogenesis. We hypothesized that besides oro-laryngeal cancer, oral inflammatory states, such as periodontitis, may also influence the chemokine profile of oral fluid. The aim of this study was to characterize the chemokine isoforms in the oral fluid of patients with periodontitis and in the oral fluid of patients with head and neck cancer. Using enzyme-linked immunosorbent assays (ELISA), it was found that the concentrations of CXCL8, CXCL10, and CCL14 were significantly elevated in the oral fluids of the cancer patients. However, periodontitis did not significantly alter the chemokine levels in oral fluid. Identification of chemokine isoforms by a proteomic approach using a newly developed three-step purification procedure was applied on the oral fluid of head and neck cancer and periodontitis patients and on the conditioned medium from carcinoma cells. Carcinoma cells produced predominantly intact CXCL1, CXCL2, CXCL8, and CCL2, whereas CXCL8 also appeared in a truncated, more active, form. Unfortunately, the chemokine concentrations in oral fluids were too low to allow full biochemical identification of the modified isoforms. However, the chemokine profile of head and neck cancer significantly changed after therapy, indicating that it is a useful parameter in clinical practice.

Interactions between chemokines and enzymes are vital in immunoregulation. Structural protein citrullination by peptidylarginine deiminase (PAD) has been associated with autoimmunity. In this report, we identified a novel naturally occurring posttranslational modification of chemokines, that is, the deimination of arginine at position 5 into citrulline of CXC chemokine ligand 10 (CXCL10) by rabbit PAD and human PAD2. Citrullination reduced (>/= 10-fold) the chemoattracting and signaling capacity of CXCL10 for CXC chemokine receptor 3 (CXCR3) transfectants; however, it did not affect CXCR3 binding. On T lymphocytes, though, citrullinated CXCL10 remained active but was again weaker than authentic CXCL10. PAD was also able to convert CXCL11, causing an impairment of CXCR3 signaling and T-cell activation, though less pronounced than for CXCL10. Similarly, receptor binding properties of CXCL11 were not altered by citrullination. However, deimination decreased heparin binding properties of both CXCL10 and CXCL11. Overall, chemokines are the first immune modulators reported of being functionally modified by citrullination. These data provide new structure-function dimensions for chemokines in leukocyte mobilization, disclosing an anti-inflammatory role for PAD. Additionally because citrullination has severe consequences for chemokine biology, this invites to reassess the involvement and impact of PAD and citrullinated peptides in inflammation, autoimmunity, and hematologic disorders.

Chemokines affect inflammation and cancer through leukocyte attraction and angiogenesis. Here, we demonstrate that CXCL4L1/platelet factor-4 variant (PF-4var), a highly angiostatic chemokine, is poorly chemotactic for phagocytes and is inducible in monocytes by inflammatory mediators but remained undetectable in macrophages and neutrophils. In addition, CXCL4L1/PF-4var production by mesenchymal tumor cells was evidenced in vitro and in vivo by specific ELISA and immunohistochemistry. CXCL4L1/PF-4var, but not CXCL4/PF-4, was coinduced with the angiogenic chemokine CXCL6/granulocyte chemotactic protein-2 (GCP-2) by cytokines, e.g., IL-1beta and IL-17, in sarcoma cells, but not in diploid fibroblasts. Furthermore, the induction of CXCL6/GCP-2 in endothelial cells by IL-1beta was enhanced synergistically by TNF-alpha but inhibited by IFN-gamma, which synergized with IL-1beta to produce the angiostatic CXCL10/IFN-gamma-induced protein-10. These findings indicate that the equilibrium between angiostatic and angiogenic factors during inflammation and tumor progression is rather complex and differs depending on the chemokine, cell type, and stimulus. Selective intervention in the chemokine network may drastically disturb this delicate balance of angiogenesis and tissue repair. Application of angiostatic CXCL4L1/PF-4var without attraction of protumoral phagocytes may be beneficial in cancer therapy.

CXCR3 ligands were secreted by tissue fibroblasts and peripheral blood-derived mononuclear leukocytes in response to interferon-gamma (IFN-gamma) and Toll-like receptor (TLR) ligands. Subsequent purification and identification revealed the presence of truncated CXCL11 variants missing up to 6 amino acids. In combination with CD26/dipeptidyl peptidase IV, the metalloprotease aminopeptidase N (APN), identical to the myeloid cell marker CD13, rapidly processed CXCL11, but not CXCL8, to generate truncated CXCL11 forms. Truncated CXCL11 had reduced binding, signaling, and chemotactic properties for lymphocytes and CXCR3- or CXCR7-transfected cells. CD13/APN-truncated CXCL11 failed to induce an intracellular calcium increase but was still able to bind and desensitize CXCR3 for intact CXCL11 signaling. CXCL11 efficiently bound to CXCR7, but CXCL11 was not able to induce calcium signaling or ERK1/2 or Akt phosphorylation through CXCR7. CD26-truncated CXCL11 failed to attract lymphocytes but still inhibited microvascular endothelial cell (HMVEC) migration. However, further processing of CXCL11 by CD13 resulted in significant reduction of inhibition of HMVEC migration. Taken together, during inflammation or cancer, CXCL11 processing by CD13 may lead to a reduced number of tumor-infiltrating lymphocytes and in a more angiogenic environment.

Mice with a disrupted IFN-gamma system are remarkably susceptible to experimental autoimmune diseases, such as collagen-induced arthritis (CIA), which rely on the use of CFA. The inflammatory lesions of these IFN-gamma knockout (KO) mice are characterized by an excessive proportion of neutrophils. Here, we show that the increased severity of CIA in IFN-gammaR KO as compared with wild-type mice is accompanied by increased levels of the CXC chemokine granulocyte chemotactic protein-2 (GCP-2), a major neutrophil-attracting chemokine in mice. We demonstrated that the heat-killed mycobacteria present in CFA elicited production of GCP-2 in mouse embryo fibroblast cultures and that this production was inhibited by IFN-gamma. Inhibition of GCP-2 production by IFN-gamma was STAT-1-dependent. IFN-gamma receptor KO mice treated with neutralizing anti-GCP-2 antibodies were protected from CIA, indicating the in vivo importance of GCP-2 in the pathogenesis of CIA. Our data support the notion that one of the mechanisms whereby endogenous IFN-gamma mitigates the manifestations of CIA consists of inhibiting production of GCP-2, thereby limiting mobilization and infiltration of neutrophils, which are important actors in joint inflammation. These results may also be applicable to other experimental models of autoimmunity that rely on the use of CFA.

CXC chemokines are potent attractants of neutrophil granulocytes, T cells or natural killer cells. Toll-like receptors (TLR) recognize microbial components and are also activated by endogenous molecules possibly implicated in autoimmune arthritis. In contrast to CXC chemokine ligand 8 (CXCL8), no CXC chemokine receptor 3 (CXCR3) ligand (ie CXCL9, CXCL10 and CXCL11) was induced by bacterial TLR ligands in human microvascular endothelial cells (HMVEC). However, peptidoglycan (PGN), double-stranded (ds) RNA or lipopolysaccharide (LPS) (TLR2, TLR3 or TLR4 ligands, respectively) synergized with interferon-gamma (IFN-gamma) at inducing CXCL9 and CXCL10. In contrast, enhanced CXCL11 secretion was only obtained when IFN-gamma was combined with TLR3 ligand. Furthermore, flagellin, loxoribine and unmethylated CpG oligonucleotide (TLR5, TLR7 and TLR9 ligands, respectively) did not enhance IFN-gamma-dependent CXCR3 ligand production in HMVEC. In analogy with TLR ligands, tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta), in combination with IFN-gamma, synergistically induced CXCL9 and CXCL11 in HMVEC and human fibroblasts, two fundamental cell types delineating the joint cavity. Etanercept, a humanized soluble recombinant p75 TNF-receptor/IgG(1)Fc fusionprotein, neutralized synergistic CXCL9 production induced by TNF-alpha plus IFN-gamma, but not synergy between IFN-gamma and the TLR ligands PGN or LPS. Synovial chemokine concentrations exemplify the physiopathological relevance of the observed in vitro chemokine production patterns. In synovial fluids of patients with spondylarthropathies (ie ankylosing spondylitis or psoriatic arthritis) or rheumatoid arthritis, significantly enhanced CXCL9, but not CXCL11 levels, were detected compared to concentrations in synovial fluids of patients with metabolic crystal-induced arthritis. Thus, CXCL9 is an important chemokine in autoimmune arthritis.

The synovial cavity constitutes the ideal stage to study the interplay between microbial Toll-like receptor (TLR) ligands and cytokines. Infiltrated leukocytes and synovial fibroblasts produce cytokine- and chemokine-induced proteases for remodeling the extracellular matrix. The regulation of chemokine function for attraction and activation of leukocytes constitutes a key feature in host immunity and resolution of inflammation after infection. Enhanced levels of the CXC chemokine ligand (CXCL9)/monokine induced by interferon-gamma (IFN-gamma) and CXCL11/IFN-inducible T cell alpha chemoattractant, two chemoattractants for activated T cells and natural killer cells, and ligands for CXC chemokine receptor 3 (CXCR3) were detected in the synovial fluid of septic arthritis compared with osteo- and crystal arthritis patients. In vitro, IFN-gamma and TLR3 ligation by double-stranded RNA (dsRNA) induced the expression of CXCL9 and CXCL11 in leukocytes and skin-muscle fibroblasts, whereas ligation of TLR2, TLR4, TLR5, and TLR9 by peptidoglycan (PGN), lipopolysaccharide (LPS), flagellin, and unmethylated CpG oligonucleotides, respectively, did not. PGN and LPS, but not unmethylated CpG oligonucleotides, even inhibited IFN-gamma-induced CXCL9 and CXCL11 expression in leukocytes. In sharp contrast, in fibroblasts, the TLR ligands PGN, dsRNA, LPS, and flagellin synergized with IFN-gamma for the production of CXCL9 and CXCL11. Although TLR ligands stimulate leukocytes to produce CXCL8/interleukin-8 during the early innate defense, they contribute less to the production of CXCR3 ligands, whereas fibroblasts are important sources of CXCR3 ligands. These results illustrate the complex interaction between cytokines and TLR ligands in infection.

The collaborative program of the Transcultural Psychosocial Organization (TPO) provides a community-oriented and culturally sensitive public health response to the psychosocial problems of refugees and victims of organized violence. This paper describes the 9-step model that TPO has developed as a blueprint for each new intervention. Beneficiaries participate in determining priorities and there is an orientation toward culturally competent training, capacity-building, and sustainability. Two cases, one related to Sudanese refugees in Uganda and the other to internally displaced persons and returnees in postwar Cambodia, show how the TPO intervention protocol is adapted to local settings. The paper provides preliminary evaluative comments on the model's performance.

The CXC chemokine IFN-gamma-inducible protein-10 (IP-10/CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T cells and natural killer cells. Peripheral blood mononuclear cells (PBMC) produce low but significant amounts of IP-10/CXCL10 protein upon stimulation with double-stranded (ds) RNA, the Toll-like receptor 3 (TLR3) ligand. IFN-gamma is a superior IP-10/CXCL10inducer. The bacterial TLR4 and TLR2 ligands, LPS and peptidoglycan (PGN), inhibit IFN-gamma- or dsRNA-dependent IP-10/CXCL10 production in PBMC, whereas IL-8/CXCL8 production was enhanced. In fibroblasts a different picture emerges with IFN-gamma inducing moderate and dsRNA provoking strong IP-10/CXCL10 production. Furthermore, treatment of fibroblasts with IFN-gamma in combination with bacterial LPS or PGN results in a synergistic production of IP-10/CXCL10 and IL-8/CXCL8. The synergistic induction of IP-10/CXCL10 in fibroblasts is reflected by significantly enhanced IP-10/CXCL10 concentrations in synovial fluids of septic compared to osteoarthritis patients to reach on average higher levels than those of IL-8/CXCL8. These high amounts of IP-10/CXCL10 produced by connective tissue fibroblasts not only attract CXCR3 expressing activated Th1 cells and natural killer cells to sites of infection but may also antagonize the CCR3 dependent attraction of Th2 lymphocytes and exert CXCR3-independent, defensin-like antibacterial activity.