A pilot cross-sectional study of non-communicable diseases in TB household contacts.

BACKGROUND: Data on the prevalence of non-communicable diseases (NCDs) in TB household contacts (HHCs) are limited, yet important to inform integrated screening and care for NCD within contact investigations. It is also unclear if screening these contacts reveals more people with NCDs than individuals in the same neighbourhood. METHOD: We conducted a pilot cross-sectional study in South Africa and Tanzania, enrolling adult HHCs of TB and individuals in neighbourhood households (controls). We inquired about known NCD and systematically measured blood pressure, and tested for spot blood glucose and haemoglobin A1c. RESULTS: We enrolled 203 adult contacts of 111 persons with TB and 160 controls. Among contacts, respectively 12.2% (95% CI 8.3-17.6) and 39.7% (95% CI 33.1-46.7) had diabetes and hypertension, compared to 14.1% (95% CI 9.2-21.0) and 44.7% (95% CI 36.9-52.7) among controls. More than half of NCDs were newly identified. We did not find a significant difference in the prevalence of at least one NCD between the two groups (OR 0.85, 95% CI 0.50-1.45, adjusted for age and sex). CONCLUSIONS: We found a high prevalence of undiagnosed NCDs among contacts, suggesting a potential benefit of integrating NCD screening and care within contact investigations. Screening in the same community might similarly find undiagnosed NCDs.

CONTEXTE: Les données sur la prévalence des maladies non transmissibles (NCD, pour l'anglais « non-communicable diseases ¼) chez les contacts familiaux (HHC, pour l'anglais « household contacts ¼) de personnes atteintes de TB sont restreintes, mais elles revêtent une grande importance pour le dépistage et la prise en charge intégrée des NCD dans le cadre des enquêtes sur les contacts. De plus, on ignore si le dépistage de ces contacts permet de détecter davantage de personnes atteintes de NCD par rapport aux les individus résidant dans le même quartier. MÉTHODE: Nous avons réalisé une étude pilote transversale en Afrique du Sud et en Tanzanie, au cours de laquelle nous avons recruté des adultes HHC de personnes atteintes de TB et des individus vivant dans les ménages voisins (témoins). Nous les avons interrogés sur les NCD connues et avons systématiquement mesuré la pression artérielle, ainsi que réalisé des tests de de glycémie et d'hémoglobine glyquée. RÉSULTATS: Un total de 203 contacts adultes de 111 personnes atteintes de TB et 160 témoins ont été répertoriés. Parmi ces contacts, respectivement 12,2% (IC à 95% 8,3­17,6) et 39,7% (IC à 95% 33,1­46,7) souffraient de diabète et d'hypertension, contre 14,1% (IC à 95% 9,2­21,0) et 44,7% (IC à 95% 36,9­52,7) chez les témoins. Plus de la moitié des NCD ont été récemment découvertes. Aucune disparité significative n'a été observée dans la prévalence d'au moins une NCD entre les deux groupes (OR 0,85 ; 95% CI 0,50­1,45, ajusté pour l'âge et le sexe). CONCLUSIONS: Nous avons observé une fréquence élevée de NCDs non diagnostiquées parmi les contacts, ce qui indique qu'il pourrait être potentiellement bénéfique d'inclure le dépistage et les soins des NCD dans les enquêtes sur les contacts. Le dépistage au sein de la même communauté pourrait également révéler des NCD non diagnostiquées.

Using indocyanine green angiography to achieve complete engraftment of pectoralis major myocutaneous flaps.

Although the pectoralis major myocutaneous (PMMC) flap is among the useful reconstructive materials following oral cancer ablation, this flap has an unstable blood circulation that could result in partial necrosis of the skin paddle. This report describes the usefulness of indocyanine green angiography (ICGA) to achieve complete engraftment of the PMMC flap. Five patients with oral cancer underwent reconstruction with a PMMC flap after cancer ablation. During the skin paddle design and flap elevation, the blood supply to the flap was assessed by ICGA. Areas of the skin paddle that showed no ICG fluorescence were excised. Consequently, prior to transfer to the recipient site, the blood supply to all flaps was confirmed with indocyanine green visible at the edge of the skin paddle, and complete engraftment was achieved without partial necrosis. Based on the results observed, ICGA would make a useful contribution to complete engraftment of the PMMC flap.

TB preventive treatment among pregnant women with HIV.

BACKGROUND: The WHO recommends TB preventive treatment (TPT) for people living with HIV, including pregnant women. Uptake of this policy recommendation in this subpopulation and country alignment with WHO guidance is unclear.METHODS: We conducted a policy review in 38 WHO high TB and TB-HIV burden countries to assess if the uptake of TPT policy among pregnant women living with HIV was in line with the WHO´s 2018 Updated and Consolidated Guidelines for Programmatic Management for LTBI. Data sources included TB national guidelines and HIV/AIDS/ART national guidelines, complemented by results from a previous survey on policy uptake held at the WHO.RESULTS: Uptake of WHO policy to provide TB preventive treatment among women with HIV accessing antenatal care was moderate: 64% (23 of 36 countries) explicitly recommended at least one clinical guideline or policy recommendation on screening, testing or treatment of LTBI among pregnant women living with HIV. There was considerable variation between countries on the stages in pregnancy that TPT should be provided. Two countries (5%) provided clinical monitoring recommendations for pregnant women.CONCLUSIONS: There is moderate uptake of TPT policy for pregnant women with HIV. Failure to provide TPT as part of antenatal or prevention of mother-to-child services is a missed opportunity for TB control.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Therapeutic indications for sinonasal topical steroid treatment and its effects on eosinophilic chronic rhinosinusitis after endoscopic sinus surgery.

OBJECTIVE: This study evaluated the post-operative indications for sinonasal topical steroid treatment using a corticosteroid (steroid)-eluting, sinus-bioabsorbable device and its effects in patients with eosinophilic chronic rhinosinusitis. METHOD: Post-operative courses were investigated in two groups: group A with patients who underwent sinonasal topical steroid treatment, and group B with control patients who did not. RESULTS: Group A was significantly younger than group B (p < 0.01), and the pre-operative computed tomography score was significantly higher in group A than in group B (p < 0.05). In the post-operative stage, the nasal symptoms questionnaire component of olfactory loss and the post-operative endoscopic appearance score were significantly worse in group A than in group B (p < 0.01). CONCLUSION: These data suggest that younger age, more severe rhinosinusitis and post-operative olfactory loss led to the need for sinonasal topical steroid treatment to prevent relapsing inflammation after functional endoscopic sinus surgery in patients with eosinophilic chronic rhinosinusitis.

Early detection of Niemann-pick disease type C with cataplexy and orexin levels: continuous observation with and without Miglustat.

STUDY OBJECTIVES: Niemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings. METHODS: Ten patients with NPC were included in the study (5 males and 5 females). NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients. RESULTS: Six NPC patients with cataplexy had low or intermediate orexin levels. In 4 cases without cataplexy, their orexin levels were normal. In 5 cases with Miglustat treatment, their symptoms stabilized or improved. For cases without Miglustat treatment, their conditions worsened generally. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels. DISCUSSION: Our study indicates that orexin level measurements can be an early alert of potential NPC. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients' NPC pathophysiology. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients. CONCLUSION: The NPC patients with cataplexy had low or intermediate orexin levels. In the cases without cataplexy, their orexin levels were normal. Our study suggests that orexin measurements can serve as an early alert for potential NPC; furthermore, they could be a marker of therapy monitoring during a treatment.

Evidence of different climatic adaptation strategies in humans and non-human primates.

To understand human evolution it is critical to clarify which adaptations enabled our colonisation of novel ecological niches. For any species climate is a fundamental source of environmental stress during range expansion. Mammalian climatic adaptations include changes in size and shape reflected in skeletal dimensions and humans fit general primate ecogeographic patterns. It remains unclear however, whether there are also comparable amounts of adaptation in humans, which has implications for understanding the relative importance of biological/behavioural mechanisms in human evolution. We compare cranial variation between prehistoric human populations from throughout Japan and ecologically comparable groups of macaques. We compare amounts of intraspecific variation and covariation between cranial shape and ecological variables. Given equal rates and sufficient time for adaptation for both groups, human conservation of non-human primate adaptation should result in comparable variation and patterns of covariation in both species. In fact, we find similar amounts of intraspecific variation in both species, but no covariation between shape and climate in humans, contrasting with strong covariation in macaques. The lack of covariation in humans may suggest a disconnect in climatic adaptation strategies from other primates. We suggest this is due to the importance of human behavioural adaptations, which act as a buffer from climatic stress and were likely key to our evolutionary success.

Screening tools to exclude active pulmonary TB in high TB burden countries: systematic review and meta-analysis.

To examine the use of symptoms, chest X-ray (CXR) abnormalities, and combinations of symptoms and CXR in excluding active pulmonary tuberculosis (TB) before treating for latent tuberculous infection (LTBI) in high TB burden countries. We updated a systematic review and meta-analysis of studies on the sensitivities, specificities, predictive values, diagnostic odds ratios and areas under the curve for index tests. The analysis was conducted using the hierarchical summary receiver operating characteristic method in R software. We included 24 publications in the systematic review and meta-analysis. 'Any CXR abnormality' had the highest sensitivity (94.1%, 95%CI 85.8-97.7) among all index tests. 'CXR abnormality suggestive of TB' had a higher specificity (92.2%, 95%CI 89.7-94.1) than 'any CXR abnormality' (86.8%, 95%CI 79.7-91.7). The sensitivity for 'any TB symptom' was 73.0% (95%CI 64.1-80.4), while 'prolonged cough' of ≥2 weeks had a specificity of 94.3% (95%CI 92.2-95.9). There was no significant difference in the sensitivity and specificity of all screening tools stratified by human immunodeficiency virus (HIV) settings, with the exception of 'CXR abnormality suggestive of TB', which had a significantly higher sensitivity in low than in high HIV prevalence settings (effect estimate 2.26, 95%CI 0.69-3.82; P = 0.002). In countries with a high TB burden, the absence of any TB symptom and any CXR abnormality can be used to exclude active pulmonary TB before initiating treatment for LTBI in household contacts aged ≥5 years of patients with bacteriologically confirmed pulmonary TB. .

Policies and practices on the programmatic management of LTBI: a survey in the African Region.

BACKGROUND: Although the management of latent tuberculous infection (LTBI) is a core component of the End TB Strategy, there is limited information about the status of implementation of such interventions in most African countries. METHODS: A web-based survey involving the 47 countries of the African Region was conducted between November 2016 and April 2017. RESULTS: The questionnaire was completed by 32/47 (68.1%) National TB Programme managers or their delegates. LTBI guidelines were available in four countries (12.5%), while 13 (40.6%) had an LTBI section in their national TB guidelines; there was no significant association with socio-economic conditions and funding allocation. LTBI diagnosis was mostly based on clinical evaluation to rule out active disease, rather than on systematic use of the tuberculin skin test. Respectively 23 (71.8%) and 17 countries (53.1%) reported providing treatment to child contacts aged <5 years and people living with the human immunodeficiency virus (PLHIV). Over two thirds of respondent countries had ongoing activities targeting at least one of the aforementioned high-risk groups. A recording and reporting system for LTBI-related data on child contacts and PLHIV was available in respectively 14 and 12 countries; 7 countries had an LTBI monitoring and evaluation plan. CONCLUSIONS: These data suggest that greater effort is needed to appropriately scale up LTBI policies in the African Region.

Three-month weekly rifapentine plus isoniazid for tuberculosis preventive treatment: a systematic review.

BACKGROUND: Uptake of preventive treatment for tuberculosis (TB) remains poor. A 3-month regimen of rifapentine (RPT) plus isoniazid (INH) (3HP) could facilitate its scale-up. We conducted a systematic review to assess the effects of 3HP compared with daily 6- or 9-month INH monotherapy. METHODS: We searched the following databases to identify randomised controlled trials: PubMed, Embase, the Web of Science, Cochrane Central Register of Controlled Trials, three ongoing trial registers and conference abstracts up to 24 January 2017. Where possible, we pooled data using a random-effects model. RESULTS: Four studies were included. Of those, we included two studies that compared 3HP with daily 6- or 9-month INH (6/9H) among adults with human immunodeficiency virus (HIV) co-infection, one among HIV-negative adults and one among predominantly HIV-negative children and adolescents. Risk of active TB was not significantly different between 3HP and 6/9H (risk ratio [RR] 0.73, 95%CI 0.23-2.29, in adults with HIV; RR 0.44, 95%CI 0.18-1.07, in adults without HIV; RR 0.13, 95%CI 0.01-2.54, in children and adolescents). Risk of hepatotoxicity was significantly lower in the 3HP group among adults with HIV (RR 0.26, 95%CI 0.12-0.55) and those without HIV (RR 0.16, 95%CI 0.10-0.27). 3HP was also associated with a higher completion rate in all subgroups. CONCLUSIONS: HP was shown to have a preventive effect similar to that of INH monotherapy, with fewer adverse events and higher completion rates. 3HP can contribute significantly to the scale-up of preventive treatment.

The assessment of surgical and non-surgical treatment of stage II medication-related osteonecrosis of the jaw.

BACKGROUND: Non-surgical treatment has generally been recommended for stage II medication-related osteonecrosis of the jaw (MRONJ) in preference to surgery. However, non-surgical treatment is not empirically effective. The aim of this study was to evaluate whether surgical or non-surgical treatment leads to better outcomes for stage II MRONJ. MATERIAL AND METHODS: In this retrospective study, surgery was performed in a total of 28 patients while 24 patients underwent non-surgical treatment. The outcomes of both treatment approaches after 6 months were evaluated and statistically compared. In addition, risk factors for surgical and non-surgical treatments were assessed for each. RESULTS: Surgical treatment in 25 patients (89.3%) resulted in success, with failure in 3 patients (10.7%). Non-surgical treatment was successful for 8 patients (33.3%) and failed in 16 patients (66.7%). There was therefore a significant difference between surgical and non-surgical treatment outcomes (P<0.01). Regarding risk factors, in non-surgical treatment primary diseases, medications, and drug holiday had a significant effect on outcomes (P<0.01). Risk factors for surgical treatment could not be clarified. CONCLUSIONS: Surgical treatment is more effective than non-surgical treatment for stage II MRONJ, and drug holiday, primary disease, and medication constitute risk factors in non-surgical treatment.

Usefulness of 11C-methionine-PET for predicting the efficacy of carbon ion radiation therapy for head and neck mucosal malignant melanoma.

The aim of this study was to determine whether l-methyl-[11C]-methionine (MET) positron emission tomography (PET) allows the prediction of outcomes in patients with head and neck mucosal malignant melanoma treated with carbon ion radiation therapy (CIRT). This was a retrospective cohort study involving 85 patients who underwent a MET-PET or MET-PET/computed tomography (CT) examination before and after CIRT. MET uptake in the tumour was evaluated semi-quantitatively using the tumour-to-normal tissue ratio (TNR). Local recurrence, metastasis, and outcome predictions were studied in terms of TNR before CIRT (TNRpre), TNR after CIRT (TNRpost), and the TNR change ratio. Kaplan-Meier curves revealed significant differences between patients with higher TNRpre values and those with lower TNRpre values in regard to local recurrence, metastasis, and outcome (log-rank test P<0.0001 for all three). There were also significant differences in metastasis rates and outcomes between patients with higher and lower TNRpost values (log-rank test P=0.0105 and P=0.027, respectively). The Cox proportional hazards model revealed TNRpre to be a factor significantly influencing the risk of local recurrence (hazard ratio (HR) 29.0, P<0.001), risk of metastasis (HR 2.67, P=0.024), and the outcome (HR 6.3, P<0.001). MET-PET or MET-PET/CT is useful for predicting the outcomes of patients with head and neck mucosal malignant melanoma treated with CIRT.