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Introduces a series of articles on economics. Economic theory of transition periods; Articulation of different forms of production and distribution organization within the economy; Mobilization of resources for accumulation and their distribution between the state and economy.

Background: Disability and loss of function are acknowledged as important problems for people living with COPD, but there is a need for validated tools to assess them., Research Question: The Late-Life Function and Disability Instrument (LLFDI) was originally validated for community-dwelling older adults. The full instrument has not been validated to assess disability and loss of function in people with COPD., Methods: People with COPD from 6 European countries completed the LLFDI as part of an observational study. Its validity was assessed in terms of 1) levels and distribution of LLFDI domain and subdomain scores; 2) floor and ceiling effects; 3) instrument structure (3 domains, 7 subdomains) by confirmatory factor analysis; and 4) construct validity by (i) convergent validity, based on Spearman correlation with COPD-relevant and related constructs (functional exercise capacity, severity of dyspnea and COPD-related health status), and (ii) known-groups validity, based on the distribution of LLFDI scores according to COPD-meaningful groups (disease severity, age groups and use of a walking aid)., Results: The study included 605 participants (aged 68±8 years, 37% female, FEV1 54±20%pred.). Most had impaired disability and function levels. We observed no floor effects and a ceiling effect in only two subdomains. Confirmatory factor analysis showed a moderate model fit for all LLFDI domains. Most of the correlations met our hypotheses (73%), with moderate to strong correlations for function domain (r min-max 0.25-0.70), followed by disability-limitation domain (r min-max 0.15-0.54), and weakest correlations in the disability-frequency domain (r min-max 0.04-0.41). The disability-limitation and function domains differed by disease severity, age group and use of a walking aid. The disability-frequency domain differed by disease severity and use of a walking aid, but not by age groups., Conclusion: The LLFDI, a valid patient-reported outcome to investigate disability and function, has proven good construct validity in people with COPD.

Background: Pulmonary rehabilitation (PR) is a well-established intervention for patients with COPD, but access, uptake and completion are low. This retrospective propensity-matched study aimed to analyse equivalence from a hybrid PR modality against conventional PR., Methods: Between 2013 and 2019, 214 patients with COPD with valid baseline physical activity assessments enrolled in conventional PR for three times per week for 3 months. In 2021-2022, 44 patients with COPD enrolled in 3 months of hybrid PR, introducing two providers: once per week in the outpatient centre and two times per week in a primary care setting near the patient's home. All sessions were supervised. Propensity score matching (1:1) was performed. Equivalence between both programmes was analysed for exercise capacity with the equivalence margins of ±30 m on the 6-min walk distance (6MWD). Clinical outcomes, accessibility and adherence were compared using t-tests., Results: 44 patients (mean±sd age 67±8 years; forced expiratory volume in 1 s (FEV 1 ) 47±15% predicted; 6MWD 355±122 m) in the hybrid PR group were matched to 44 patients (mean±sd age 66±8 years; FEV 1 46±17% predicted; 6MWD 354±103 m) in the conventional PR group. Equivalence on the increase in 6MWD could not be confirmed; nevertheless, both groups improved their 6MWD clinically significantly (hybrid PR change 63 m (90% CI 43-83 m); conventional PR change 39 m (90% CI 26-52 m)). Changes in quality of life and symptoms were similar. Dropout in hybrid PR (23%) was comparable to conventional PR (27%) (p=0.24). Adherence in both groups was high and accessibility was better for patients following hybrid PR., Conclusion: Hybrid PR can be offered as an effective alternative to conventional PR, if patients are willing to take up the offer., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest., (Copyright ©The authors 2024.)

Background: Starting rehabilitation soon after an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is crucial to diminish the detrimental effects of this acute event on muscle function. However, uptake in outpatient pulmonary rehabilitation is low., Objectives: To design and test a feasible, acceptable and accessible exercise training program (ETP) in primary care for patients experiencing an AECOPD., Design: (1) A literature review and qualitative study to develop an ETP and (2) A feasibility study of the ETP implemented in primary care., Methods: (1) The development of the ETP proceeded in several phases with input from different stakeholders through focus group discussions. (2) Patients experiencing a moderate or severe AECOPD were included and followed the ETP for two weeks with a physiotherapist in primary care. Interviews with the participants took place and patients were given the choice to complete the eight-week program., Results: (1) Six discussion sessions took place. The ETP contained a flexible set of progressively more difficult exercises applicable in a primary care practice. (2) Eight patients experiencing a moderate (n = 1) or severe (n = 7) AECOPD were included. Patients started the first physiotherapy session 5 (2-6) days after the start of their symptoms or hospital discharge. Seven patients wanted to complete the ETP., Conclusions: An ETP in primary care is feasible, acceptable and accessible for patients experiencing a moderate or severe AECOPD, and for physiotherapists. The effectiveness of this ETP on muscle function and physical activity is currently under investigation in a RCT. CONTRIBUTION OF THE PAPER., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients' blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all. The patients had normal counts of Langerhans cells (LCs) and dermal macrophages in the skin but lacked dermal DCs. Thus, FLT3L is required for B cell and DC development in mice and humans. However, unlike its murine counterpart, human FLT3L is required for the development of monocytes but not NK cells., Competing Interests: Declaration of interests J.-L.C. serves on the scientific advisory boards of ADMA Biologics Inc., Kymera Therapeutics, and Elixiron Immunotherapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite the importance of gait as a determinant of falls, disability and mortality in older people, understanding of gait impairment in COPD is limited. This study aimed to identify differences in gait characteristics during supervised walking tests between people with COPD and healthy controls., Methods: We searched 11 electronic databases, supplemented by Google Scholar searches and manual collation of references, in November 2019 and updated the search in July 2021. Record screening and information extraction were performed independently by one reviewer and checked for accuracy by a second. Meta-analyses were performed in studies not considered at a high risk of bias., Results: Searches yielded 21 085 unique records, of which 25 were included in the systematic review (including 1015 people with COPD and 2229 healthy controls). Gait speed was assessed in 17 studies (usual speed: 12; fast speed: three; both speeds: two), step length in nine, step duration in seven, cadence in six, and step width in five. Five studies were considered at a high risk of bias. Low-quality evidence indicated that people with COPD walk more slowly than healthy controls at their usual speed (mean difference (MD) -19 cm·s -1 , 95% CI -28 to -11 cm·s -1 ) and at a fast speed (MD -30 cm·s -1 , 95% CI -47 to -13 cm·s -1 ). Alterations in other gait characteristics were not statistically significant., Conclusion: Low-quality evidence shows that people with COPD walk more slowly than healthy controls, which could contribute to an increased falls risk. The evidence for alterations in spatial and temporal components of gait was inconclusive. Gait impairment appears to be an important but understudied area in COPD., Competing Interests: Conflict of interest: A. Polhemus is a paid employee of Merck & Co, Inc. and IQVIA AG. S.C. Buttery reports educational speaker fees for Pulmonx. J. Garcia-Aymerich reports speaker honoraria from Chiesi and a grant from AstraZeneca paid to her institution for a COVID-19-related project and is also a paid advisory board member for AstraZeneca. All other authors report no conflicts of interest., (Copyright ©The authors 2024.)

Objectives: Physical activity is reduced in patients with interstitial lung disease (ILD) and physical inactivity is related to poor health outcomes. We investigated the effect of a telecoaching intervention to improve physical activity in patients with ILD., Methods: Eighty patients with ILD were randomized into the intervention or control group. Patients in the intervention group received a 12-week telecoaching program including a step counter, a patient-tailored smartphone application, and coaching calls. Patients in the control group received usual care. Physical activity (primary outcome), physical fitness and quality of life were measured at baseline and 12 weeks later with an accelerometer, 6-min walking test and quadriceps muscle force and the King's Brief Interstitial Lung Disease questionnaire (K-BILD)., Results: Participation in telecoaching did not improve physical activity: between-group differences for step count: 386 ± 590 steps/day, p = .52; sedentary time: 4 ± 18 min/day, p = .81; movement intensity: 0.04 ± 0.05 m/s 2 , p = .45). Between-group differences for the 6-min walking test, quadriceps muscle force and K-BILD were 14 ± 10 m, p = .16; 2 ± 3% predicted, p = .61; 0.8 ± 1.7 points, p = .62 respectively., Conclusions: Twelve weeks of telecoaching did not improve physical activity, physical fitness or quality of life in patients with ILD. Future physical or behavioural interventions are needed for these patients to improve physical activity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: While patients with COPD often cite weather conditions as a reason for inactivity, little is known about the relationship between physical activity (PA) and weather conditions. The present study investigated the association of day-to-day weather changes on PA in patients with COPD and investigated patient characteristics related to being more or less influenced by weather conditions., Methods: In this longitudinal analysis, device-based day-by-day step counts were objectively measured in COPD patients for up to 12 months. Daily meteorological data (temperature, precipitation, wind speed, hours of sunlight and daylight) were linked to the daily step count and individual and multivariable relationships were investigated using mixed-model effects. Individual R 2 was calculated for every subject to investigate the estimated influence of weather conditions on a patient level and its relationship with patient characteristics., Results: We included 50 patients with a mean±sd follow-up time of 282±93 days, totalling 14 117 patient-days. Daily temperature showed a positive linear pattern up until an inflexion point, after which a negative association with increasing temperature was observed (p<0.0001). Sunshine and daylight time had a positive association with PA (p<0.0001). Precipitation and wind speed were negatively associated with PA (p<0.0001). The median per-patient R 2 for overall weather conditions was 0.08, ranging from 0.00 to 0.42. No strong associations between patient characteristics and per-patient R 2 were observed., Conclusion: Weather conditions are partly associated with PA in patients with COPD, yet the overall explained variance of PA due to weather conditions is rather low and varied strongly between individuals., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Physical activity (PA) is low in patients with Chronic Obstructive Pulmonary Disease (COPD). Identifying modifiable and non-modifiable correlates of PA give understanding of the individual behavior and provide future directions for PA enhancing interventions. As PA is complex and multidimensional, it should be embedded within a thorough framework., Objective: To identify correlates of PA in a comprehensive COPD population based on a broad ecological model, including physiological, psychological, socio-demographic and environmental dimensions., Methods: PA was objectively measured using the Dynaport Movemonitor and a comprehensive data collection of physiological, psychological, socio-demographic and environmental factors were collected. Bivariable and multivariable regression analyses (including principle component analysis) were executed., Results: For this cross-sectional analysis, we included 148 patients with COPD and valid PA data (mean (SD) age 68 (7) years, FEV1 57 (17) % predicted, 5613 (3596) steps per day). Significant bivariable associations were found for physiological (exercise capacity, muscle force, lung function, symptoms, comorbidities), psychological (e.g. fatigue, motivation, perceived difficulty with PA), socio-demographic (dog owning, use of activity tracker) and environmental (season, daylight, temperature) factors. Based on the multivariable regression model, exercise capacity, beliefs on motivation, importance and self-confidence regarding PA and weather conditions were independent correlates of mean steps per day (R 2  = 0.35). Movement intensity during walking was only independently associated with exercise capacity and age (R 2  = 0.41)., Conclusion: Although a wide range of potential influence factors were evaluated, variance in PA was only partly explained, supporting that PA is a complex behavior which is difficult to predict., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Astrid Blondeel reports financial support was provided by Research Foundation Flanders. Heleen Demeyer reports financial support was provided by Research Foundation Flanders. Fien Hermans reports financial support was provided by Research Foundation Flanders. Marieke Wuyts reports financial support was provided by Research Foundation Flanders., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: This article investigates the extent and sources of late diagnosis of cancer in Tanzania, demonstrating how delayed diagnosis was patterned by inequities rooted in patients' socio-economic background and by health system responses. It provides evidence to guide equity-focused policies to accelerate cancer diagnosis., Methods: Tanzanian cancer patients (62) were interviewed in 2019. Using a structured questionnaire, respondents were encouraged to recount their pathways from first symptoms to diagnosis, treatment, and in some cases check-ups as survivors. Patients described their recalled sequence of events and actions, including dates, experiences and expenditures at each event. Socio-demographic data were also collected, alongside patients' perspectives on their experience. Analysis employed descriptive statistics and qualitative thematic analysis., Results: Median delay, between first symptoms that were later identified as indicating cancer and a cancer diagnosis, was almost 1 year (358 days). Delays were strongly patterned by socio-economic disadvantage: those with low education, low income and non-professional occupations experienced longer delays before diagnosis. Health system experiences contributed to these socially inequitable delays. Many patients had moved around the health system extensively, mainly through self-referral as symptoms worsened. This "churning" required out-of-pocket payments that imposed a severely regressive burden on these largely low-income patients. Causes of delay identified in patients' narratives included slow recognition of symptoms by facilities, delays in diagnostic testing, delays while raising funds, and recourse to traditional healing often in response to health system barriers. Patients with higher incomes and holding health insurance that facilitated access to the private sector had moved more rapidly to diagnosis at lower out-of-pocket cost., Conclusions: Late diagnosis is a root cause, in Tanzania as in many low- and middle-income countries, of cancer treatment starting at advanced stages, undermining treatment efficacy and survival rates. While Tanzania's policy of free public sector cancer treatment has made it accessible to patients on low incomes and without insurance, reaching a diagnosis is shown to have been for these respondents slower and more expensive the greater their socio-economic disadvantage. Policy implications are drawn for moving towards greater social justice in access to cancer care., (© 2022. The Author(s).)

Background: Exacerbations affect the disease trajectory of patients with COPD and result in an acute drop of functional status and physical activity. Timely detection of exacerbations by non-medical healthcare professionals is needed to counteract this decline. The use of digital health applications in patient interaction allows embedded detection of exacerbations. However, it is unknown if this is an effective way to pick up exacerbations., Method: We investigated the detection of exacerbations in patients with COPD enrolled in a physical activity coaching program, by prompting a weekly question on changes in medication via the smartphone application. Data on response rate and occurrence of exacerbations were collected., Results: Response rate to the medication question, evaluated in 42 patients, was 72% ( n = 497). A change in medication was reported through the smartphone application in 38 (7.6%) of the answered questions. The response rate was significantly lower at 6 months follow-up compared to the first month ( p =0.03). When evaluating the occurrence of adverse events in a subset of patients who completed 6 months of follow-up ( n = 27), 18 exacerbations were registered in eight patients, of which 10 of these exacerbations (56%) were picked up by the medication question in the coaching application., Conclusion: Electronic interaction through a weekly medication question, embedded in a smartphone application, is feasible to support the detection of the occurrence of COPD exacerbations and can be used complementary to regular forms of detecting exacerbations. Compliance and smartphone literacy should be optimized when further using this method to report on COPD exacerbations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Blondeel, Demeyer, Breuls, Wuyts, Glorie, De Maeyer, Janssens and Troosters.)

The prediction of SARS-CoV-2 immunity by commercially available serologic tests will be crucial to assess the efficacy of vaccination. We used plaque reduction neutralization testing as the reference standard to evaluate the diagnostic performance of six commercial serologic tests for monitoring SARS-CoV-2 neutralizing antibodies. Euroimmun ELISA anti-spike 1 IgG, Euroimmun anti-spike 1 IgG QuantiVac ELISA, Elecsys Anti-nucleocapsid protein total antibodies, Elecsys Anti-receptor-binding domain total antibodies, VIDAS anti-spike subdomain IgG, and Microblot-Array COVID-19 IgG assay were performed on 228 sera from 89 healthcare workers who participated in a six-month seroprevalence survey. Although all immunoassays demonstrated similar performances, VIDAS SARS-CoV-2 IgG and Euroimmun QuantiVac IgG (area under the curve 0.96 and 0.95 respectively) showed the better ability to detect Nabs. Except for the Elecsys Anti-SARS-CoV-2 and the Elecsys Anti-SARS-CoV-2 S assays, the commercial serologic tests evaluated here showed a significant decrease of antibody titers in the 6-month follow-up samples. Depending on the immunoassay, 21% to 33% of the participants became seronegative, and 16.9% had a loss of neutralizing antibodies. Microblot-Array assay results showed cross-reactivity with HCoVNL63 in only one sample, and this sample showed SARS-CoV-2 neutralizing capacity. In conclusion, our results support the use of VIDAS SARS-CoV-2 IgG, Euroimmun Anti-SARS-CoV-2 ELISA IgG, Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA IgG and Microblot-Array COVID-19 IgG assays to monitor neutralizing antibody response following natural SARS-CoV-2 infection. These immunoassays could facilitate the prediction of post-vaccine protection in the long term and the allocation of booster doses., (Copyright © 2021. Published by Elsevier B.V.)

Background: International policy towards access to essential medicines in Africa has focused until recently on international procurement of large volumes of medicines, mainly from Indian manufacturers, and their import and distribution. This emphasis is now being challenged by renewed policy interest in the potential benefits of local pharmaceutical production and supply. However, there is a shortage of evidence on the role of locally produced medicines in African markets, and on potential benefits of local production for access to medicines. This article contributes to filling that gap., Methods: This article uses WHO/HAI data from Tanzania for 2006 and 2009 on prices and sources of a set of tracer essential medicines. It employs innovative graphical methods of analysis alongside conventional statistical testing., Results: Medicines produced in Tanzania were equally likely to be found in rural and in urban areas. Imported medicines, especially those imported from countries other than Kenya (mainly from India) displayed 'urban bias': that is, they were significantly more likely to be available in urban than in rural areas. This finding holds across the range of sample medicines studied, and cannot be explained by price differences alone. While different private distribution networks for essential medicines may provide part of the explanation, this cannot explain why the urban bias in availability of imported medicines is also found in the public sector., Conclusions: The findings suggest that enhanced local production may improve rural access to medicines. The potential benefits of local production and scope for their improvement are an important field for further research, and indicate a key policy area in which economic development and health care objectives may reinforce each other.

There is controversy on the role of IgM memory and switched memory B lymphocytes in the Ab response to T cell-independent and T cell-dependent Ags. We transplanted SCID/SCID mice with human B lymphocyte subsets and immunized them with heat-inactivated Streptococcus pneumoniae or with a pneumococcal vaccine. Inactivated S. pneumoniae and soluble pneumococcal capsular polysaccharides elicited an IgM anti-polysaccharide and anti-protein Ab response from IgM memory B lymphocytes and an IgG anti-polysaccharide and anti-protein response from switched memory B lymphocytes. In addition to the IgM Ab response, IgM memory B cells elicited an IgG anti-polysaccharide and anti-protein Ab response after immunization with inactivated S. pneumoniae or soluble pneumococcal capsular polysaccharides. In conclusion, our findings provide evidence for a versatile role of IgM memory B cells in T-independent and T-dependent immune responses.

The capsular polysaccharides (caps-PS) of Streptococcus pneumoniae are classified as thymus-independent antigens. Nevertheless, T lymphocytes can modulate the antibody response to caps-PS. In this study, we show that anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) treatment, along with administration of caps-PS to BALB/c mice, resulted in a dose-dependent generation of a strong caps-PS-specific antibody response. Anti-CTLA-4 treatment had no effect on the immunoglobulin G (IgG) antibody production in athymic nu/nu mice. Anti-CTLA-4 treatment stimulated the IgG antibody production in severe combined immunodeficiency (SCID)/SCID mice reconstituted with CTLA-4(-/-) B lymphocytes and wild-type T lymphocytes. This excluded the possibility that anti-CTLA-4 enhanced antibody production by direct interaction with B lymphocytes. Anti-CTLA-4 treatment enhanced the antibody production in SCID/SCID mice reconstituted with B lymphocytes and CD4(+) and CD8(+) T lymphocytes but not in SCID/SCID mice reconstituted with B lymphocytes in the absence of CD4(+) and/or CD8(+) cells. Administration of anti-CTLA-4 in BALB/c mice but not in nu/nu mice resulted in a markedly increased production of interleukin (IL)-2, IL-4, and interferon-gamma. Taken together, these data strongly suggest a role of T lymphocytes and CTLA-4 in the regulation of the antibody response to caps-PS.

Protection against infection with pneumococci is provided by anti-capsular polysaccharide (caps-PS) Abs. We investigated whether CD40 ligand (CD40L) plays a role in T lymphocyte-mediated regulation of the immune response to caps-PS, which are considered thymus-independent Ags. Administration of MR1, an antagonist mAb against murine CD40L, in BALB/c mice immunized with Pneumovax resulted in an inhibition of the IgM and IgG Ab response for various caps-PS serotypes. Evidence for the involvement of CD4(+) T lymphocytes in the Ab response to caps-PS was obtained in SCID/SCID mice that, when reconstituted with B lymphocytes and CD4(+) T lymphocytes, mounted a higher specific IgM response compared with SCID/SCID mice reconstituted with only B lymphocytes. This helper effect of CD4(+) T lymphocytes was abrogated by MR1. Blocking CD40L in vitro decreased the IgM response to caps-PS and abolished the helper effect of CD4(+) T lymphocytes. CD8(+) T lymphocyte-depleted murine spleen cells mounted a higher in vivo immune response than total murine spleen cells, which provided evidence for a suppressive role of CD8(+) T lymphocytes on the anti-caps-PS immune response. CD4(+) T lymphocyte-depleted murine spleen cells, leaving a B and CD8(+) T lymphocyte fraction, elicited only a weak in vivo and in vitro Ab response, which was enhanced after MR1 administration. In summary, our data provide evidence that T lymphocytes contribute to the regulation of the anti-caps-PS immune response in a CD40L-dependent manner.