Participatory design of a music aural rehabilitation programme.

OBJECTIVES: Many cochlear implant (CI) users wish to enjoy music but are dissatisfied by its quality as perceived through their implant. Although there is evidence to suggest that training can improve CI users' perception and appraisal of music, availability of interactive music-based aural rehabilitation for adults is limited. In response to this need, an 'Interactive Music Awareness Programme' (IMAP) was developed with and for adult CI users. METHODS: An iterative design and evaluation approach was used. The process began with identification of user needs through consultations, followed by use of mock-up applications in workshops. Feedback from these were used to develop the prototype IMAP; a programme of 24 interactive sessions, enabling users to create and manipulate music. The prototype IMAP was subsequently evaluated in a home trial with 16 adult CI users over a period of 12 weeks. RESULTS: Overall ratings for the prototype IMAP were positive and indicated that it met users' needs. Quantitative and qualitative feedback on the sessions and software in the prototype IMAP were used to identify aspects of the programme that worked well and aspects that required improvement. The IMAP was further developed in response to users' feedback and is freely available online. CONCLUSIONS: The participatory design approach used in developing the IMAP was fundamental in ensuring its relevance, and regular feedback from end users in each phase of development proved valuable for early identification of issues. Observations and feedback from end users supported a holistic approach to music aural rehabilitation.

Aural rehabilitation through music workshops for cochlear implant users.

BACKGROUND: It has been reported that after speech perception, music appreciation is the second most commonly expressed requirement among cochlear implant (CI) recipients. Certain features of music are known to be more readily accessible; however, provision of music rehabilitation for adult CI users is limited. PURPOSE: A series of music workshops were organized to (1) enable attendees to explore which aspects of music they are able to perceive and appreciate; (2) raise awareness of listening strategies, technology, and rehabilitation resources for music; and (3) develop ideas, and prototype software, for inclusion in a music rehabilitation program. The therapeutic value of music workshops was concurrently investigated. RESEARCH DESIGN: A qualitative, longitudinal study was used. Two consultation meetings were held before a series of nine music workshops that occurred over a period of 5 mo. STUDY SAMPLE: Five adult CI users participated in consultations before the workshops. Twenty-eight adult CI users from the South of England Cochlear Implant Centre attended at least one of the workshops. INTERVENTION: Participants could attend as many workshops as they wished. Each workshop lasted between 2 to 2.5 hr and included individual computer-based and group activities. DATA COLLECTION AND ANALYSIS: Responses to open-ended questions were transcribed in the consultation meetings and used to develop workshop activities. A preworkshop survey was used to determine attendees' aspirations and expectations. Postworkshop surveys were used to qualitatively and quantitatively evaluate attendees' immediate reactions to the workshop content, software, and perceived benefits. A 2-month, postworkshop survey evaluated the longer-term impact of the workshops. RESULTS: Overall reaction to the workshops and prototype software was positive. All attendees indicated that they anticipated changing how they engaged with music as a result of the workshops, and data from the preworkshop and postworkshop surveys suggest a positive change in listening habits. CONCLUSIONS: The workshops proved to be an effective means of simultaneously encouraging music exploration in a social and safe environment and obtaining feedback on prototype rehabilitation materials. Survey data suggested that through group listening and practical activities, certain aspects of music can be accessible and rewarding through a CI, leading to positive changes in attitude and behavior toward music.

Tuberculosis after commencing antiretroviral therapy for HIV infection is associated with elevated CXCL9 and CXCL10 responses to Mycobacterium tuberculosis antigens.

BACKGROUND: Commencing antiretroviral therapy (ART) in human immunodeficiency virus-infected patients with treated or unrecognized Mycobacterium tuberculosis disease may trigger tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) or ART-associated tuberculosis (ART-TB). We have shown that whole-blood interferon-gamma release assays may aid in the prediction and diagnosis of ART-TB. Here, we investigate interferon-gamma-inducible chemokines CXCL9 and CXCL10. METHODS: CXCL9 and CXCL10 responses to region of difference 1 (RD1) antigens and purified protein derivative (PPD) were assayed in plasma from whole-blood cultures collected before and after 4, 12, and 24 weeks of ART from 15 TB-IRIS cases, 11 ART-TB cases, and matched controls. RESULTS: Relative to matched controls, ART-TB cases had elevated CXCL10 responses to RD1 antigens pre-ART (P = 0.02) and to PPD and RD1 antigens over 24 weeks of ART (P ≤ 0.02 and P ≤ 0.03). In contrast, TB-IRIS cases had higher CXCL10 responses to RD1 antigens before and after 4 weeks of ART only (P = 0.04 for both). CXCL9 responses to PPD and RD1 antigens were similar but less pronounced in ART-TB cases and did not differ between TB-IRIS cases and controls. CXCL10 responses to RD1 antigens performed as well as, or better than, IFN-γ responses in the prediction and diagnosis of ART-TB. CONCLUSIONS: Tuberculosis after commencing ART is associated with increased CXCL10 and, to a lesser extent, CXCL9 responses to M. tuberculosis antigens. Assessment of antigen-induced CXCL10 responses to RD1 antigens may assist in the prediction and diagnosis of ART-TB.

Short communication: Plasma levels of vitamin D in HIV patients initiating antiretroviral therapy do not predict immune restoration disease associated with Mycobacterium tuberculosis.

Immune restoration disease associated with Mycobacterium tuberculosis (TB IRD) is clinically important among HIV patients commencing antiretroviral therapy in countries where tuberculosis is endemic. Vitamin D affects dendritic cell and T cell function and the antimicrobial activity of monocytes. Plasma levels of vitamin D and polymorphisms in the vitamin D receptor may affect tuberculosis, and HIV infection associates with vitamin D deficiency. Here we assess whether plasma vitamin D levels may predict TB IRD. Samples were available from prospective studies of TB IRD in Cambodia (26 cases), India (19 cases), and South Africa (29 cases). IRD cases and controls from each site were similar in age and baseline CD4(+) T cell count. Plasma samples were assessed using 25(OH) vitamin D immunoassay plates. DNA samples were available from a subset of patients and were genotyped for the VDR FokI (F/f) [C/T, rs10735810] SNP. When data from each cohort were pooled to assess ethnic/geographic differences, 25(OH)D levels were higher in Cambodian than Indian or South African patients (p<0.0001) and higher in South African than Indian patients (p<0.0001). TB IRD was not associated with differences in levels of 25(OH)D in any cohort (p=0.36-0.82), irrespective of the patients' prior TB diagnoses/treatment. Carriage of the minor allele of VDR FokI (F/f) was marginally associated with TB IRD in Indian patients (p=0.06) with no association in Cambodians. Neither plasma levels of vitamin D nor the vitamin D allele will usefully predict TB IRD in diverse populations from TB endemic regions.

Mycobacterial antibody levels and immune restoration disease in HIV patients treated in South East Asia.

AIM: Immune restoration disease (IRD) associated with Mycobacterium tuberculosis parallels the reconstitution of a pathogen-specific Th1 response. However, it is not clear whether humoral responses to M. tuberculosis antigens also rise, or whether antibody levels predict IRD. Here, humoral immunity to M. tuberculosis antigens was investigated in four Asian cohorts. METHODS: Plasma samples were obtained from longitudinal prospective studies of HIV patients beginning antiretroviral therapy (ART) in New Delhi (India), Kuala Lumpur (Malaysia), Jakarta (Indonesia) and Phnom Penh (Cambodia). IgG antibodies to purified protein derivative, lipoarabinomannan and 38-kDa antigens of M. tuberculosis were quantitated using in-house ELISAs. IRD was defined as exacerbated symptoms of tuberculosis in patients on anti-tuberculosis therapy or a novel presentation of tuberculosis on ART. RESULTS: Pre-ART IgG levels to purified protein derivative, lipoarabinomannan and 38-kDa antigen were similar in the IRD and control groups from each site. Compared with non-IRD controls, a higher proportion of IRD patients had elevated IgG levels to lipoarabinomannan (defined as a greater than twofold increase) over 12 weeks of ART. However, this trend was not significant for the other antigens and longitudinal analyses did not reveal clear rises in antibody levels at the time of IRD. CONCLUSION: Levels of antibody to mycobacterial antigens do not predict IRD, but levels of antibody reactive with lipoarabinomannan rise during an IRD in some patients.

The search for biomarkers of immune restoration disease associated with Mycobacterium tuberculosis in HIV patients beginning antiretroviral therapy.

Immune restoration disease associated with Mycobacterium tuberculosis is a complication of antiretroviral therapy seen in a subset of HIV-1 patients soon after they commence antiretroviral therapy. It is characterized by a 'paradoxical' worsening of treated tuberculosis or an 'unmasking' of subclinical tuberculosis. As antiretroviral therapy becomes increasingly available in countries with a high prevalence of tuberculosis, this form of immune restoration disease will become more common. Here we summarize biomarkers that may illuminate immunopathogenesis and assist in diagnosis.

Mediators of innate and adaptive immune responses differentially affect immune restoration disease associated with Mycobacterium tuberculosis in HIV patients beginning antiretroviral therapy.

BACKGROUND: Initiation of antiretroviral therapy (ART) in human immunodeficiency virus patients with treated or unrecognized Mycobacterium tuberculosis infection may result in tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) or ART-associated tuberculosis (ART-TB), respectively. Both conditions appear to be immune restoration disease but their immunopathogenesis is not completely understood. METHODS: Chemokines and cytokines produced by the innate immune system (CCL2, CXCL8, CXCL9, CXCL10, and interleukin 18 [IL-18]) were assayed in plasma from unstimulated whole blood cultures obtained from 15 TB-IRIS case patients, 11 ART-TB case patients, and matched control participants over 24 weeks of ART. RESULTS: When compared with control participants, levels of IL-18 and CXCL10 were higher in TB-IRIS case patients (P = .002 and .006, respectively), whereas CCL2 was lower (P = .006). IL-18 level was higher in ART-TB case patients (P = .002), but CXCL10 was only marginally higher (P = .06). When TB-IRIS case patients were compared with ART-TB case patients, IL-18 was higher in ART-TB (P = .03), whereas CXCL10 was higher in TB-IRIS (P = .001). Using receiver operating characteristic curves, pre-ART levels of CCL2, CXCL10, and IL-18 were predictive of TB-IRIS and additive to IFN-γ responses. CONCLUSIONS: Perturbations of the innate immune response to M. tuberculosis before and during ART may contribute to the immunopathology of TB-IRIS, whereas elevated IL-18 alone suggests adaptive immune responses predominate in ART-TB. These findings may have implications for therapy in TB-IRIS.

Interferon-γ and IL-5 production correlate directly in HIV patients co-infected with mycobacterium tuberculosis with or without immune restoration disease.

IL-5 and interferon-γ responses were investigated in mitogen-stimulated whole-blood cultures from HIV patients with and without Mycobacterium tuberculosis disease, to determine whether an imbalance of Th1/Th2 cytokines contributes to susceptibility to M. tuberculosis disease or to immune restoration disease (IRD) associated with M. tuberculosis after starting antiretroviral therapy (ART). Interferon-γ levels were constant on ART, whilst IL-5 levels generally rose over time. We suggest that increased IL-5 production reflects a recovery of CD4(+) T cell function and that a Th1/Th2 imbalance is not associated with increased susceptibility to M. tuberculosis disease or IRD associated with M. tuberculosis upon starting ART.