Interventions in the management of infection in the foot in diabetes: a systematic review

The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high‐quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections as of June 2018. This systematic review is an update of previous reviews, the first of which was undertaken in 2010 and the most recent in 2014, by the infection committee of the International Working Group of the Diabetic Foot. We defined the context of literature by formulating clinical questions of interest, then developing structured clinical questions (PICOs) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and the methodological quality. Our literature search identified a total of 15 327 articles, of which we selected 48 for full‐text review; we added five more studies discovered by means other than the systematic literature search. Among these selected articles were 11 high‐quality studies published in the last 4 years and two Cochrane systematic reviews. Overall, the outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetic foot were broadly equivalent across studies, except that treatment with tigecycline was inferior to ertapenem (±vancomycin). Similar outcomes were also reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high‐quality evidence to assess the effect of various adjunctive therapies, such as negative pressure wound therapy, topical ointments or hyperbaric oxygen, on infection related outcomes of the diabetic foot. In general, the quality of more recent trial designs are better in past years, but there is still a great need for further well‐designed trials to produce higher quality evidence to underpin our recommendations.     

A randomized clinical trial of an interactive voice response and text message intervention for individuals with hypertension

Interactive voice response and text message (IVR‐T) technology may improve hypertension control in under‐resourced settings. We conducted a randomized clinical trial to determine whether an IVR‐T intervention would improve blood pressure (BP), medication adherence and visit keeping among adults with hypertension from multiple racial and ethnic groups in primary care at an Urban Indian Health Organization in Albuquerque, New Mexico. Two hundred and ninety‐five participants were randomly assigned to IVR‐T (N = 148) or to usual care (N = 147). The IVR‐T arm received reminders for clinic visits, messages to reschedule missed clinic visits, monthly medication refill reminders, weekly motivational messages, and a blood pressure cuff. The usual care arm received no messages. The primary outcome was change in systolic BP (SBP) between baseline and 12 months. Secondary outcomes included change in SBP between baseline and 6 months, change in diastolic BP (DBP) at 6 and 12 months, self‐reported adherence at 6 months, and the proportion of missed primary care clinic appointments. The intervention did not affect SBP or DBP at 6 or 12 months. The 12‐month change in SBP/DBP was 1.66/1.10 mm Hg in usual care and 0.23/1.34 mm Hg in the intervention group (P values = .57 and .88, respectively). Self‐reported medication adherence improved comparably in both groups, and there was no difference in percentage of kept visits. Several features of study design, clinic operations, and data transfer were barriers to demonstrating effectiveness.     

Innate and adaptive immune responses during acute M. tuberculosis infection in adult household contacts in Kampala, Uganda

Contacts of active pulmonary tuberculosis (TB) patients are at risk for Mycobacterium tuberculosis (MTB) infection. Because most infections are controlled, studies during MTB infection provide insight into protective immunity. We compared immune responses of adult household contacts that did and did not convert the tuberculin skin test (TST). Innate and adaptive immune responses were measured by whole blood assay. Responses of TST converters (TSTC) were compared with persistently TST negative contacts (PTST-) and contacts who were TST+ at baseline (TST+). TLR-2, TLR-4, and IFN-γR responses to IFN-γ did not differ between the groups, nor did γδ T cell responses. T cell responses to MTB antigens differed markedly among TSTC, PTST-, and TST+ contacts. Thus, no differences in innate responses were found among the three household contact groups. However, adaptive T cell responses to MTB antigens did differ before and during MTB infection among PTST-, TSTC, and TST+ contacts.     

Child and Adolescent Mental Health Training Programs for Non-specialist Mental Health Professionals in Low and Middle Income Countries: A Scoping Review of Literature

Large treatment deficits in child and adolescent mental health (CAMH) care exist in low and middle income countries (LMICs). This study reviewed CAMH training programs for non-specialist health professionals (NSHPs) in LMICs. Multiple databases were searched for peer-reviewed articles describing programs from 2005 to 2018. Educational source materials, trainee evaluation methods, and perspectives on teaching methods, course content and scheduling were studied. Six programs were identified. NSHPs were most appreciative of training which included case-based discussions, role plays and clinical demonstrations that were relevant to local contexts. A need for less intense and more flexible timetables to enable reflection was identified. WHO’s mental health gap action program intervention guide (mhGAP-IG) and international association of child and adolescent psychiatrists and allied professionals resources should be used; they are free, easily accessible, and developed with extensive international contributions. Additionally, mhGAP-IG assessment tool encourages mutual learning, thereby iteratively enhancing training programs.

     

Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation. Comparative studies of pathology and cell wall distribution in athymic and euthymic rats.

Systemic administration of an aqueous suspension of group A streptococcal cell wall fragments to susceptible rats induces acute and chronic polyarthritis, as well as noncaseating hepatic granulomas. To gain insight into the role of the thymus in the pathogenesis of this experimental model, pathologic responses and cell wall tissue distribution were compared in congenitally athymic rats (rnu/rnu) and their euthymic littermates (NIH/rnu). Within 24 h, both rat strains developed acute arthritis, characterized by polymorphonuclear leukocytic exudate in the synovium and joint spaces. This acute process was maximal at day 3 and gradually subsided. Beginning 2-3 wk after injection, the euthymic, but not the athymic, rats developed the typical exacerbation of arthritis, characterized by synovial cell hyperplasia with villus formation and T helper/inducer lymphocyte-rich mononuclear cell infiltration. This process eventually resulted in marginal erosions and destruction of periarticular bone and cartilage. Parallel development of acute and chronic hepatic lesions was observed. Bacterial cell wall antigen distribution and persistence were similar in the athymic and euthymic rats. Cell wall antigens were demonstrated in the cytoplasm of cells within subchondral bone marrow, synovium, liver, and spleen, coincident with the development of the acute lesions, and persisted in these sites, although in decreasing amounts, for the duration of the experiment. Our findings provide evidence that the acute and chronic phases of the experimental model are mechanistically distinct. The thymus and functional thymus derived-lymphocytes appear not to be required for the development of the acute exudative disease but are essential for the development of chronic proliferative and erosive disease. Induction of disease is dependent upon cell wall dissemination to and persistence in the affected tissues.