Diabetes characteristics and long-term management needs in diabetic TB patients.

BACKGROUND: Diabetes mellitus (DM) is common among patients with TB. We assessed DM characteristics and long-term needs of DM-TB patients after completing TB treatment.METHODS: Newly diagnosed TB patients with DM were recruited for screening in a randomised clinical trial evaluating a simple algorithm to improve glycaemic control during TB treatment. DM characteristics, lifestyle and medication were compared before and after TB treatment and 6 months later. Risk of cardiovascular disease (CVD), albuminuria and neuropathy were assessed after TB treatment.RESULTS: Of 218 TB-DM patients identified, 170 (78%) were followed up. Half were males, the mean age was 53 years, 26.5% were newly diagnosed DM. High glycated haemoglobin at TB diagnosis (median 11.2%) decreased during TB treatment (to 7.4% with intensified management and 8.4% with standard care), but this effect was lost 6 months later (9.3%). Hypertension and dyslipidemia contributed to a high 10-year CVD risk (32.9% at month 6 and 35.5% at month 12). Neuropathy (33.8%) and albuminuria (61.3%) were common. After TB treatment, few patients used CVD-mitigating drugs.CONCLUSION: DM in TB-DM patients is characterised by poor glycaemic control, high CVD risk, and nephropathy. TB treatment provides opportunities for better DM management, but effort is needed to improve long-term care.

Educational counselling of patients with combined TB and diabetes mellitus: a randomised trial.

SETTING: Newly diagnosed pulmonary TB with diabetes mellitus (DM) comorbidity attending clinics in Bandung City, Indonesia. OBJECTIVE: To describe the effect of educational counselling on patients' knowledge about TB (transmission, treatment, risk factors) and DM (symptoms, treatment, complications, healthy lifestyle), adherence to medication, and to assess characteristics associated with knowledge. DESIGN: All patients received counselling and were then randomised to either structured education on TB-DM, combined with clinical monitoring and medication adjustment (intervention arm), or routine care (control arm). Knowledge and adherence were assessed using a questionnaire. RESULTS: Baseline and 6-month questionnaires were available for 108 of 150 patients randomised (60/76 in the intervention arm and 48/74 in the control arm). Patients knew less about DM than about TB. There was no significant difference in the proportion with knowledge improvement at 6 months, both for TB (difference of differences 14%; P = 0.20) or for DM (10%; P = 0.39) between arms. Intervention arm patients were more likely to adhere to taking DM medication, with fewer patients reporting ever missing oral DM drugs than those in the control arm (23% vs. 48%; P = 0.03). Higher education level was associated with good knowledge of both TB and DM. CONCLUSIONS: Structured education did not clearly improve patients' knowledge. It was associated with better adherence to DM medication, but this could not be attributed to education alone. More efforts are needed to improve patients' knowledge, especially regarding DM.

CONTEXTE: Patients atteints de diabète sucré (DM) ayant récemment reçu un diagnostic de TB pulmonaire consultant dans les cliniques de la ville de Bandung, Indonésie. OBJECTIF: Décrire l'effet de conseils éducatifs sur les connaissances des patients en matière de TB (transmission, traitement, facteurs de risque), de DM (symptômes, traitement, complications, mode de vie sain) et d'observance thérapeutique, et évaluer les caractéristiques associées à ces connaissances. MÉTHODE: Tous les patients ont reçu des conseils et ont ensuite été randomisés dans l'un des deux groupes suivants : programme d'éducation structuré sur la TB-DM associé à un suivi clinique et à un ajustement thérapeutique (groupe d'intervention) ou prise en charge de routine (groupe témoin). Les connaissances et l'observance ont été évaluées par questionnaire. RÉSULTATS: Les questionnaires administrés à l'inclusion et à 6 mois étaient disponibles pour 108 des 150 patients randomisés (60/76 dans le groupe d'intervention et 48/74 dans le groupe témoin). Les connaissances des patients étaient moins bonnes sur le DM que sur la TB. Aucune différence significative n'a été observée entre les groupes dans la proportion de patients dont les connaissances s'étaient améliorées à 6 mois, tant pour la TB (différence des différences 14% ; P = 0,20) que pour le DM (10% ; P = 0,39). Les patients du groupe d'intervention étaient plus susceptibles d'observer correctement leur traitement antidiabétique. Moins de patients ont en effet rapporté avoir manqué une dose de leur traitement antidiabétique oral par rapport au groupe témoin (23% vs. 48% ; P = 0,03). Un niveau d'éducation plus élevé a été associé à de bonnes connaissances sur la TB et le DM. CONCLUSIONS: Le programme d'éducation structuré n'a pas amélioré de manière évidente les connaissances des patients. Ce programme a été associé à une meilleure observance du traitement antidiabétique, mais cela n'a pas pu être attribué au seul programme d'éducation. Davantage d'efforts sont nécessaires pour améliorer les connaissances des patients, notamment sur le DM.

Early chest X-ray in persons with presumptive tuberculosis increases Xpert® MTB/RIF diagnostic yield and efficiency.

Adult presumptive tuberculosis (TB) patients (n = 1690) were screened for TB using a questionnaire, chest X-ray (CXR) and sputum microscopy for acid-fast bacilli (AFB); Mycobacterium tuberculosis culture was performed for 74% of the patients and Xpert® MTB/RIF was done for 17.2%. Among patients recruited, 943 (55.8%) were diagnosed with TB, of whom 870 (92.3%) were bacteriologically confirmed and 73 (7.7%) were clinically diagnosed on the basis of CXR. Using CXR prior to culture or Xpert testing reduces the number needed to screen from 7.6 to 5.0. Using CXR to triage for culture or Xpert testing reduces the number of missed cases and increases the efficiency of culture and Xpert testing.

Des patients adultes présumés atteints de TB (n = 1690) ont été dépistés à l'aide d'un questionnaire, d'une radiographie pulmonaire (CXR) et d'une microscopie de crachats à la recherche des bacilles acido-alcoolo-résistants; une culture de Mycobacterium tuberculosis a été réalisée chez 74% des patients et un test Xpert® MTB/RIF, chez 17,2%. Parmi les patients recrutés, 943 (55,8%) ont eu un diagnostic de TB, dont 870 (92,3%) ont été confirmés par bactériologie et 73 (7,7%) ont été diagnostiqués sur la CXR. Recourir à la CXR avant la culture ou le test Xpert réduit le nombre requis pour dépister un cas de 7,6 à 5,0. L'utilisation de la CXR pour le triage avant la culture ou le test Xpert réduit les cas manqués et augmente l'efficacité de l'utilisation de la culture et de l'Xpert.

Se investigó de la tuberculosis (TB) en pacientes adultos con presunción clínica de la enfermedad (n = 1690) mediante un cuestionario, la radiografía de tórax (CXR) y la baciloscopia del esputo; se practicó el cultivo para Mycobacterium tuberculosis en 74% de los pacientes y la prueba Xpert® MTB/RIF en 17,2%. De los pacientes que participaron se diagnosticó la TB en 943 (55,8%), de los cuales 870 (92,3%) con confirmación bacteriológica y 73 (7,7%) con diagnóstico clínico a partir de la CXR. El hecho de realizar la CXR o la prueba Xpert antes del cultivo disminuye de 7,6 a 5,0 el número de pacientes que deben someterse a detección. El uso de la CXR para seleccionar los casos en que se debe practicar el cultivo o la prueba Xpert disminuye los casos pasados por alto y aumenta la eficiencia del uso del cultivo y la prueba Xpert.

HIV prevalence among men who have sex with men in New Zealand 1985-2009: 25 years of public health monitoring.

Annual population-based estimates of the number of men who have sex with men (MSM) with diagnosed HIV infection (HIV prevalence pool), and the proportion of all MSM this represents (HIV prevalence), have been insufficiently described over the long term. We investigated the dynamic effects of ongoing HIV diagnoses, lower mortality due to treatment and growth in the MSM population over time on these two epidemic indicators using national HIV/AIDS surveillance data in New Zealand, 1985-2009. The diagnosed HIV prevalence pool rose 79% between 1989 and 1999, and 137% between 1999 and 2009. Estimates of diagnosed HIV prevalence as a proportion of MSM were 0.2% of MSM in 1985, and were between 1.5% and 5.0% of MSM by 2009. New Zealand continues to have a relatively low-prevalence HIV epidemic among MSM; however, the number of MSM living with diagnosed infection is growing rapidly 25 years after HIV testing was introduced.

Selective modulation of intracortical inhibition by low-intensity Theta Burst Stimulation.

OBJECTIVE: Theta Burst Stimulation (TBS) is a repetitive transcranial magnetic stimulation paradigm which has effects on both excitatory and inhibitory intracortical pathways when applied at an intensity of 80% of active motor threshold. As intracortical inhibitory pathways have a lower threshold for activation than excitatory pathways, we sought to determine whether it was possible to selectively target cortical inhibitory circuitry by reducing the intensity of TBS to 70% of active motor threshold. METHODS: Motor evoked potentials (MEPs), short latency intracortical facilitation (SICF), intracortical facilitation (ICF) and short interval intracortical inhibition (SICI) were measured at baseline, 5-20 and 20-35 min following continuous (cTBS) and intermittent (iTBS) low-intensity TBS in nine healthy subjects. RESULTS: Low-intensity cTBS significantly reduced SICI 5-20 min following stimulation, whilst having no effect on MEPs, SICF or ICF. Low-intensity iTBS had no effect on SICI, MEPs, SICF or ICF. CONCLUSIONS: It is possible to selectively target intracortical inhibitory networks for modulation by low-intensity TBS, however, responses may critically depend upon the particular paradigm chosen. SIGNIFICANCE: These findings have important implications for the treatment of neurological disorders where abnormal levels of intracortical inhibition are present, such as Parkinson's disease and focal hand dystonia and requires further investigation.

Unlinked anonymous HIV prevalence among New Zealand sexual health clinic attenders: 2005-2006.

This unlinked anonymous study aimed at determining the prevalence of HIV among sexual health clinic attenders having blood samples taken for syphilis and/or hepatitis B serology in six major New Zealand cities over a 12-month period in 2005-2006. Overall, seroprevalence was five per 1000 (47/9439). Among men who have sex with men (MSM), the overall prevalence and that of previously undiagnosed HIV were 44.1 and 20.1 per 1000, respectively. In heterosexual men, the overall prevalence was 1.2 per 1000 and in women 1.4 per 1000. HIV remains to be concentrated among homosexual and bisexual men. Comparison with a previous survey in 1996-1997 suggests an increase in the prevalence of undiagnosed HIV among MSM and also an increase in the number of MSM attending sexual health clinics. The low prevalence of HIV among heterosexuals suggests no extensive spread into the groups identified at risk of other sexually transmitted infections.

Good outcome in HIV-infected refugees after resettlement in New Zealand: population study.

BACKGROUND: The aims of this study were to determine the clinical characteristics on arrival and the subsequent clinical outcome of HIV-infected UN quota refugees who settled in New Zealand during the last 11 years and to estimate their rate of HIV transmission. METHODS: A population study was conducted. Data were provided by the Mangere Refugee Resettlement Centre, the infectious disease physicians caring for the subjects, the New Zealand AIDS Epidemiology Group and laboratories carrying out HIV viral load assays. RESULTS: One hundred of 7732 (1.3%) UN quota refugees were HIV positive; mean age 30 years, 56% were men, median initial CD4 count was 320 (range 20-1358). HIV infection was most commonly acquired by heterosexual intercourse (74%). The median follow up was 5.0 years (range 1 month to 9.7 years). Five died and 15 subjects had 16 AIDS-defining illnesses, most commonly tuberculosis (n = 10). Sixty subjects commenced highly active antiretroviral therapy of whom 36/59 (61%) had an undetectable HIV viral load after 1 year of treatment. None of the six children born to HIV-infected women in New Zealand were infected. There were two known cases of horizontal transmission of HIV infection. CONCLUSION: Although HIV-infected quota refugees often have to overcome severe social, cultural and financial handicaps, their clinical outcome is generally very good, with response rates to highly active antiretroviral therapy that are similar to other patient groups. Furthermore, they have not been a significant source of transmission of HIV infection after resettlement in New Zealand.

The preparation of liposomes using compressed carbon dioxide: strategies, important considerations and comparison with conventional techniques.

Numerous strategies are currently available for preparing liposomes, although no single method is ideal in every respect. Two methods for producing liposomes using compressed carbon dioxide in either its liquid or supercritical state were therefore investigated as possible alternatives to the conventional techniques currently used. The first technique used modified compressed carbon dioxide as a solvent system. The way in which changes in pressure, temperature, apparatus geometry and solvent flow rate affected the size distributions of the formulations was examined. In general, liposomes in the nano-size range with an average diameter of 200 nm could be produced, although some micron-sized vesicles were also present. Liposomes were characterized according to their hydrophobic drug-loading capacity and encapsulated aqueous volumes. The latter were found to be higher than in conventional techniques such as high-pressure homogenization. The second method used compressed carbon dioxide as an anti-solvent to promote uniform precipitation of phospholipids from concentrated ethanolic solutions. Finely divided solvent-free phospholipid powders of saturated lipids could be prepared that were subsequently hydrated to produce liposomes with mean volume diameters of around 5 microm.

Antimicrobial properties of liposomal polymyxin B.

The pulmonary residence time of polymyxin B has been shown to be substantially increased when administered as a liposomal formulation. The use of this system to improve the treatment of cystic fibrosis lung infections requires that the antimicrobial activity of polymyxin B is unaffected by the encapsulation process. To verify that activity against the target organism, Pseudomonas aeruginosa, was retained, the bactericidal activity and MICs of both free and encapsulated polymyxin B were determined. The roles of liposomal surface characteristics in determining interactions with bacterial cell surfaces were also investigated. Encapsulation of polymyxin B was reduced when the positively charged amphiphile, stearylamine (SA) was present, with entrapment efficiencies being lower than with neutral (egg phosphatidylcholine, EPC) or negatively charged (egg phosphatidylcholine:dicetylphosphate, EPC:DCP) formulations (EPC, 45.41% +/- 0.51%; EPC:DCP 9:1, 50.81% +/- 0.79%; EPC:SA 9:1, 31.92% +/- 2.08%, n x 3). The bactericidal activities were compared, and it was found that polymyxin B retained antimicrobial activity after encapsulation. At a polymyxin B concentration of 0.3 mg/L, both positively and negatively charged liposomal polymyxin B formulations, and free drug, killed all cells after 1 h. In contrast, neutral liposome formulations did not significantly decrease the surviving cell fraction. At 0.1 mg/L, fewer cells were killed, and all liposomal formulations produced a reduction in cell numbers, which was not significantly different from free drug. It was found that the MICs of liposomal formulations were attributable to the free drug concentration achieved through release of entrapped polymyxin B. Enhanced activity was seen only with positively charged EPC:SA liposomes and those containing distearoylphosphatidylcholine (DSPC) as the bulk phospholipid. This is likely to be the result of favourable electrostatic interactions and increased liposome:cell ratios respectively. In summary, liposome encapsulation of polymyxin B was not detrimental to antimicrobial activity, and liposome surface properties and release characteristics were important in determining interactions with bacterial cells.

Liposomal (MLV) polymyxin B: physicochemical characterization and effect of surface charge and drug association.

Neutral and charged large vortexed multilamellar hydrogenated egg phosphatidylcholine liposomes containing the polycationic antibiotic polymyxin B (PXB) were characterized with respect to lipid-drug interactions (differential scanning calorimetry), surface charge (zeta potential analysis), size (photon correlation spectroscopy) and morphology (transmission electron microscopy). These physicochemical results will be used to develop a liposomal drug delivery system for PXB that may be useful in the clinical treatment of lung infection in cystic fibrosis patients. The liposomal morphology and membrane integrity of all the preparations were unaffected by associated antibiotic. Drug encapsulation increased in the order neutral = positive < negative, the negatively charged liposomes increasing drug association 2-fold. The phase transition temperature of neutral and positive liposomes was not significantly affected by PXB. Drug-loaded negative liposomes showed a decreased phase transition possibly due to attractive electrostatic interactions between drug and lipid that tended to increase drug penetration and destabilize the liposome bilayer. Drug loading did not affect liposome size. However, both empty and loaded negative liposomes were significantly smaller (approx. 1 micron) than neutral and positive (approx. 2.5 microns) liposomes. Increased encapsulation with negative liposomes is therefore due not to an increase in the entrapped volume but to electrostatic interactions.

Interrelationships between left ventricular volume and output during exercise in healthy subjects.

To better characterize the relationship between left ventricular volume response and improved ventricular ejection and output during supine exercise in normal subjects, 36 healthy asymptomatic volunteers (age 39 +/- 17 yr) were studied with radionuclide ventriculography during recumbent bicycle ergometry. Relative changes in left ventricular end-diastolic and end-systolic volume were measured at rest and during exercise by a modification of the radionuclide counts-based method that accounted for variability in stress blood pool counts. A biphasic response was noted in left ventricular end-diastolic volume with an initial increase in early exercise (8.5 +/- 11% at 200 kpm/min and 11 +/- 12% at 300 kpm/min) followed by a progressive and significant decline at peak exercise (-3.3 +/- 18% at 547 +/- 140 kpm/min; P < 0.05). There was substantial variation in end-diastolic volume response at peak exercise in the group as a whole, which could be more closely related to changes in end-systolic volume (r = 0.84, P < 0.0001) than in heart rate (r = -0.57, P < 0.01) or age (r = 0.36, P < 0.05) of the study subjects. Despite the decline in ventricular filling, systolic function appeared to improve dramatically at peak exercise (change in left ventricular ejection fraction 15.5 +/- 6.4, P < 0.0001). Although not directly related to increasing systolic ejection, end-diastolic volume was directly related to the percent change in stroke volume at peak exercise among the study subjects (r = 0.88, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of age and gender on left ventricular response to supine exercise in asymptomatic normal subjects.

The performance of normal subjects during radionuclide ventriculography has been related to age, but the combined effects of age and sex on exercise ventricular function are not well described. We studied 55 normal volunteers, 27 men (age = 30 +/- 10 years) and 28 women (age = 33 +/- 14 years), free of chest pain syndromes, during supine rest/exercise radionuclide ventriculography performed to fatigue. Resting left ventricular ejection fraction did not differ between male and female subjects (64 +/- 5.4 vs 64 +/- 6.1; p = NS). Both the peak left ventricular ejection fraction (78 +/- 4.4 vs 72 +/- 9.2; p less than 0.001) and the change in ejection fraction with exercise (14 +/- 4.0 vs 7.9 +/- 7.0; p less than 0.001) were significantly greater in men compared to respective values in women. Regression analysis showed that sex (r = 0.51; p less than 0.001) but not age (r = -0.18; p = 0.19) was a significant predictor of change in ejection fraction with exercise. Data on left ventricular volume response to exercise, available in 43 subjects, revealed that men had a greater percentage of decline in end-systolic volume with exercise than women (-47 +/- 15 vs -24 +/- 26; p less than 0.001). It is concluded that sex exerts a significant influence on normal left ventricular response to fatigue-limited supine exercise and that the gender difference is mediated, in part, by left ventricular end-systolic volume response to exercise.