Objective dysphonia quantification in vocal fold paralysis: comparing nonlinear with classical measures

Clinical acoustic voice recording analysis is usually performed using classical perturbation measures including jitter, shimmer and noise-to-harmonic ratios. However, restrictive mathematical limitations of these measures prevent analysis for severely dysphonic voices. Previous studies of alternative nonlinear random measures addressed wide varieties of vocal pathologies. Here, we analyze a single vocal pathology cohort, testing the performance of these alternative measures alongside classical measures.

We present voice analysis pre- and post-operatively in unilateral vocal fold paralysis (UVFP) patients and healthy controls, patients undergoing standard medialisation thyroplasty surgery, using jitter, shimmer and noise-to-harmonic ratio (NHR), and nonlinear recurrence period density entropy (RPDE), detrended fluctuation analysis (DFA) and correlation dimension. Systematizing the preparative editing of the recordings, we found that the novel measures were more stable and hence reliable, than the classical measures, on healthy controls.

RPDE and jitter are sensitive to improvements pre- to post-operation. Shimmer, NHR and DFA showed no significant change (p > 0.05). All measures detect statistically significant and clinically important differences between controls and patients, both treated and untreated (p < 0.001, AUC > 0.7). Pre- to post-operation, GRBAS ratings show statistically significant and clinically important improvement in overall dysphonia grade (G) (AUC = 0.946, p < 0.001).

Re-calculating AUCs from other study data, we compare these results in terms of clinical importance. We conclude that, when preparative editing is systematized, nonlinear random measures may be useful UVFP treatment effectiveness monitoring tools, and there may be applications for other forms of dysphonia.
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Cotrimoxazole prophylaxis in HIV-infected individuals after completing anti-tuberculosis treatment in Thyolo, Malawi.

SETTING: Thyolo, rural southern Malawi. OBJECTIVES: To determine 1) the proportion who continue with cotrimoxazole prophylaxis for the prevention of opportunistic infections, and 2) the reasons for continuing or stopping prophylaxis, in human immunodeficiency virus (HIV) infected individuals with tuberculosis (TB) who complete anti-tuberculosis treatment. DESIGN: A cross-sectional study. METHODS: A questionnaire study of all HIV-infected TB patients who had been registered over a 3-month period to receive anti-tuberculosis treatment and cotrimoxazole prophylaxis and who had completed antituberculosis treatment 3-6 months earlier. RESULTS: Of 82 HIV-infected individuals who were alive at the time of interview, 76 (93%) were continuing with cotrimoxazole and wished to do so indefinitely. The most common reason for continuing the drug was to prevent illness associated with HIV, while the most common reason for stopping was long distances to the health facility. Ninety-six percent of patients received cotrimoxazole free of charge from a health centre. Of those who wished to continue indefinitely, the majority (63%) could not afford to pay for the drug. CONCLUSIONS: In a rural setting, the great majority of HIV-infected individuals continued with cotrimoxazole after completing anti-tuberculosis treatment. Making the drug available and providing it free of charge is essential if it is to remain accessible for longer term prevention

The timing of death in patients with tuberculosis who die during anti-tuberculosis treatment in Andhra Pradesh, South India

Background: India has 2.0 million estimated tuberculosis (TB) cases per annum with an estimated 280,000 TBrelated deaths per year. Understanding when in the course of TB treatment patients die is important for determining the type of intervention to be offered and crucially when this intervention should be given. The objectives of the current study were to determine in a large cohort of TB patients in India:- i) treatment outcomes including the number who died while on treatment, ii) the month of death and iii) characteristics associated with “early” death, occurring in the initial 8 weeks of treatment. Methods: This was a retrospective study in 16 selected Designated Microscopy Centres (DMCs) in Hyderabad, Krishna and Adilabad districts of Andhra Pradesh, South India. A review was performed of treatment cards and medical records of all TB patients (adults and children) registered and placed on standardized anti-tuberculosis treatment from January 2005 to September 2009. Results: There were 8,240 TB patients (5183 males) of whom 492 (6%) were known to have died during treatment. Case-fatality was higher in those previously treated (12%) and lower in those with extra-pulmonary TB (2%). There was an even distribution of deaths during anti-tuberculosis treatment, with 28% of all patients dying in the first 8 weeks of treatment. Increasing age and new as compared to recurrent TB disease were significantly associated with “early death”. Conclusion: In this large cohort of TB patients, deaths occurred with an even frequency throughout anti-TB treatment. Reasons may relate to i) the treatment of the disease itself, raising concerns about drug adherence, quality of anti-tuberculosis drugs or the presence of undetected drug resistance and ii) co-morbidities, such as HIV/ AIDS and diabetes mellitus, which are known to influence mortality. More research in this area from prospective and retrospective studies is needed

Input of tritium to intermediate depth water in the South Pacific

Tritium concentrations have been determined for seawater samples collected near the western boundary of the South Pacific. The deepest penetration of tritium, in terms of either depth or isopycnal surface, occurs between latitudes 14 and 30S and the penetration is greater than that observed in the mid-South Pacific during the Geochemical Ocean Sections Study (GEOSECS) cruise...

Passive Versus Active Tuberculosis Case Finding and Isoniazid Preventive Therapy Among Household Contacts in a Rural District of Malawi.

SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis

Outcomes of tuberculosis patients who start antiretroviral therapy under routine programme conditions in Malawi

SETTING: Public sector facilities in Malawi providing antiretroviral therapy (ART) to human immunodeficiency virus (HIV) positive patients, including those with tuberculosis (TB). OBJECTIVES: To compare 6-month and 12-month cohort treatment outcomes of HIV-positive TB patients and HIV-positive non-TB patients treated with ART. DESIGN: Retrospective data collection using ART patient master cards and ART patient registers. RESULTS: Between July and September 2005, 7905 patients started ART, 6967 with a non-TB diagnosis and 938 with a diagnosis of active TB. 6-month cohort outcomes of non-TB and TB patients censored on 31 March 2006 showed significantly more TB patients alive and on ART (77%) compared with non-TB patients (71%) (P < 0.001). Between January and March 2005, 4580 patients started ART, 4179 with a non-TB diagnosis and 401 with a diagnosis of active TB. 12-month cohort outcomes of non-TB and TB patients censored on 31 March 2006 showed significantly more TB patients alive and on ART (74%) compared with non-TB patients (66%) (P < 0.001). Other outcomes of default and transfer out were also significantly less frequent in TB compared with non-TB patients. CONCLUSION: HIV-positive TB patients on ART in Malawi have generally good treatment outcomes, and more patients need to access this HIV treatment

Operational research in Malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV.

BACKGROUND: In Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions. DISCUSSION: District and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART. SUMMARY: Key lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not