Integrated tuberculosis and HIV care in a resource-limited setting: experience from the Martin Preuss centre, Malawi.

OBJECTIVES: To describe the development and operation of integrated tuberculosis (TB) and HIV care at the Martin Preuss Centre, a multipartner organization bringing together governmental and non-governmental providers of HIV and TB services in Lilongwe, Malawi. METHODS: We used a case study approach to describe the integrated TB/HIV service and to illustrate successes and challenges faced by service providers. We quantified effective TB and HIV integration using indicators defined by the World Health Organization. RESULTS: The custom-designed building facilitates patient flow and infection control, and other important elements include coordinated leadership; joint staff training and meetings; and data systems prompting coordinated care. Some integrated services have worked well from the outset, such as promoting HIV testing among patients with TB (96% of patients with TB had documented HIV status in 2009). Other aspects of integrated care have been more challenging, for example achieving high uptake of antiretroviral therapy among HIV-positive TB patients and combining data from paper and electronic systems. Good TB treatment outcomes (>85% cure or completion) have been achieved among both HIV-positive and HIV-negative individuals. CONCLUSIONS: High-quality integrated services for TB and HIV care can be provided in a resource-limited setting. Lessons learned may be valuable for service providers in other settings of high HIV and TB prevalence.

Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline.

OBJECTIVES: The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second-line ART. We report outcomes for patients evaluated and initiated on second-line treatment in Malawi. METHODS: Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV-1 RNA copies/mL) and, if failure was confirmed, initiated on second-line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months. RESULTS: Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second-line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV-related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV-1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/microL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14-10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15-17.12) were risk factors for death. Baseline CD4 count <50 cells/microL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01-6.52). CONCLUSIONS: Second-line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable.

Deep brain stimulation for dystonia: outcome at long-term follow-up.

OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic option for patients with insufficient benefit from conservative treatment. METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4), generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige syndrome (1) were available for formal follow-up at three years postoperatively, and beyond up to 10 years. All patients had undergone pallidal stimulation except one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS: Maintained improvement was seen in all patients with pallidal stimulation up to 10 years after surgery except in one patient who had a relative loss of benefit in dystonia ratings but continued to have improved disability scores. After nine years of chronic thalamic stimulation there was a mild loss of efficacy which was regained when the target was changed to the pallidum in the patient with paroxysmal dystonia. There were no major complications related to surgery or to chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in general. CONCLUSION: DBS maintains marked long-term symptomatic and functional improvement in the majority of patients with dystonia.

Health-related quality of life in segmental dystonia is improved by bilateral pallidal stimulation.

In contrast to generalized dystonia, reports on the effectiveness of pallidal stimulation on quality of life in patients with segmental dystonia are sparse to date. In ten patients with idiopathic segmental dystonia we prospectively evaluated the effect of pallidal stimulation on quality of life using the SF-36 questionnaire. Parallel to the improvement of motor scores, total SF-36 scores and physical and mental health subscores improved significantly at follow-up to a mean of 17 months postoperatively. Thus, pallidal stimulation should be recognized as a promising treatment option in patients with segmental dystonia.

Chronic spinal cord stimulation in medically intractable orthostatic tremor.

BACKGROUND: Orthostatic tremor with its sense of unsteadiness when standing may have a devastating effect on affected persons. Currently, there are no other treatment options in those who do not respond or who do not tolerate medical treatment. OBJECTIVES: To report on a pilot study on spinal cord stimulation in medically intractable orthostatic tremor. METHODS: Chronic spinal cord stimulation (SCS) was performed in two patients with medically-intractable orthostatic tremor via quadripolar plate electrodes implanted at the lower thoracic spine. The electrodes were connected to implantable pulse generators. RESULTS: Subjective and objective improvement of unsteadiness was achieved within a frequency range of 50 to 150 Hz, and occurred in the presence of stimulation-induced paraesthesia. With optimized stimulation settings polygraphic electromyelogram (EMG) recordings continued to show the typical 14-16 Hz EMG activity. The beneficial effect of SCS was maintained at long-term follow-up. CONCLUSIONS: The results of this pilot study indicate that SCS may be an option in patients with otherwise intractable orthostatic tremor.

Risperidone-responsive segmental dystonia and pallidal deep brain stimulation.

A 67-year-old man with risperidone-responsive segmental dystonia underwent bilateral deep brain stimulation (DBS) of the globus pallidus internus. Prospectively, the authors assessed the Burke-Fahn-Marsden Dystonia Rating Scale in medication (M) and stimulation (S) "on"/"off" states. With DBS at 9 months, the score improved by 86% to 8.5 in M-"on"/S-"on" and 12.5 in M-"off"/S-"on." Studies of the effects of DBS and concomitant medication may be warranted in selected patients treated by DBS for dystonia.

Deep brain stimulation of the centre median-parafascicular complex in patients with movement disorders.

The centre median-parafascicular (CM-Pf) complex of the thalamus is considered to be a possible target for deep brain stimulation (DBS) in patients with movement disorders. In a prospective study on the effect of CM-Pf DBS versus somatosensory thalamic DBS on chronic neuropathic pain, three of 12 patients had additional movement disorders. Bifocal quadripolar electrodes were implanted by computed tomography guided stereotactic surgery under local anaesthesia contralaterally to the side of the pain for test stimulation. Two of the three patients with movement disorders had permanent implantation of CM-Pf electrodes. During test stimulation of the left CM-Pf complex for several days, a 67 year old woman received no benefit with respect to the neuropathic pain, but the choreoathetotic movements of her right foot ceased. As the pain syndrome was not improved, she decided not to have permanent implantation. A 74 year old man with postzoster neuralgia and allodynia enjoyed excellent relief from his pain with chronic CM-Pf DBS. In addition, improvement in the tremor at rest was noted. A 72 year old man had sustained reduction in his stump dyskinesias. Further evaluation of the possible role of the "forgotten" central and medial thalamic nuclei in the treatment of movement disorders may be warranted.

Nonoperative management of hyperparathyroidism: present and future.

Parathyroidectomy provides effective treatment for primary and secondary hyperparathyroidism with a predictable response of symptoms related to hypercalcemia and elevated parathyroid hormone. Calcium and vitamin D supplementation has reduced the need for parathyroidectomy in dialysis patients with secondary hyperparathyroidism. However, surgery continues to be the only effective treatment of primary hyperparathyroidism. Potential nonoperative treatments for hyperparathyroidism have included the use of estrogen replacement, bisphosphonates, and a new class of drugs known as calcimimetics. Hormone replacement therapy with estrogen has been reported to improve cortical bone density in postmenopausal women with asymptomatic or mildly symptomatic primary hyperparathyroidism. Calcimimetic agents are a new class of drugs that increase the sensitivity of the calcium receptor to ionized calcium. Initial studies have shown that calcimimetics can acutely lower parathyroid hormone levels in patients with primary and secondary hyperparathyroidism. These drugs are currently being evaluated in phase II clinical trials. Ultimately, these medical modalities will need to be compared to parathyroidectomy in randomized controlled clinical trials.

Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women.

The long-term clinical effects of soy protein containing various amounts of isoflavones on lipoproteins, mononuclear cell LDL receptor messenger RNA concentrations, and other selected cardiovascular risk factors are not well known. Sixty-six hypercholesterolemic, free-living, postmenopausal women were investigated during a 6-mo parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, all subjects were randomly assigned to 1 of 3 dietary groups (all with 40 g protein): a National Cholesterol Education Program (NCEP) Step 1 diet with protein from casein and nonfat dry milk (control), an NCEP Step 1 diet with protein from isolated soy protein containing moderate amounts of isoflavones (ISP56), or an NCEP Step 1 diet with protein from isolated soy protein containing high amounts of isoflavones (ISP90). Non-HDL cholesterol in both the ISP56 and ISP90 groups was reduced compared with the control group (P < 0.05), whereas total cholesterol was not changed. HDL cholesterol increased in both the ISP56 and ISP90 groups (P < 0.05), whereas the ratio of total to HDL cholesterol decreased significantly in both groups compared with the control (P < 0.05). Mononuclear cell LDL receptor messenger RNA concentrations increased in subjects consuming ISP56 or ISP90 compared with the control (P < 0.05). These results indicate that soy protein, with different amounts of isoflavones, may decrease the risk of cardiovascular disease via improved blood lipid profiles, and that the mechanism by which apolipoprotein B-containing lipoproteins were depressed may be via alterations in LDL receptor quantity or activity.

Light spectral quality effects on the growth of potato (Solanum tuberosum L.) nodal cuttings in vitro.

The effect of light spectral quality on the growth of in vitro nodal cuttings of potato (Solanum tuberosum L.) cultivars Norland, Superior, Kennebec, and Denali were examined. The different light spectra were provided by Vita-Lite fluorescent (VF) (a white light control), blue fluorescent (BF), red fluorescent (RF), low-pressure sodium (LPS), and a combination of low-pressure sodium plus cool-white fluorescent lamps (LPS/CWF). For all cultivars, stem lengths after 4 wk were longest under LPS, followed by RF, LPS/CWF, VF, and BF (in descending order). Microscopic studies revealed that cells were shortest when cultured in BF or VF environments, and were longest in RF or LPS lamp environments. The highest number of axillary branches occurred on plantlets grown with LPS or LPS/CWF, whereas the lowest number occurred with BF. No leaf or stem edema (callus or gall-like growths) occurred with LPS or LPS/CWF lighting, and no edema occurred on cv. Norland plantlets, regardless of lighting. Results suggest that shoot morphologic development of in vitro grown potato plants can be controlled by controlling irradiant spectral quality.

Multiple regression analysis of differential response to treatment in randomized controlled clinical trials.

A multiple regression model is presented for the analysis of the components of individual change in clinical trials. Of primary interest is the condition where treatment effects vary according to patient baseline level. The model differentiates the average effects of treatment from baseline-dependent treatment effects, as well as identifying regression toward the mean and temporal effects. This model is applied in the analysis of data from a clinical trial of nutritional supplementation.

Calcium supplementation reduces the risk of pregnancy-induced hypertension in an Andes population.

Previous studies have suggested that increased dietary calcium is associated with a decreased occurrence of pregnancy-induced hypertension. In this study 106 young healthy nulliparous women, residing in Quito, Ecuador, were enrolled in a double-blind, randomized, controlled clinical trial. From 24 weeks gestation until delivery they received either 2 g of elemental calcium per day or a placebo. Calcium supplementation was associated with a significantly decreased risk of pregnancy-induced hypertension, with 4.1% developing pregnancy-induced hypertension in the treatment group versus 27.9% in the placebo group. Treatment was associated with a decrease in both systolic and diastolic blood pressure over the course of pregnancy. In addition, there was a small but significant increase in serum ionized calcium levels in the calcium-supplemented group during the treatment period.

Histomorphometric effects of calcium or calcium plus 25-hydroxyvitamin D3 therapy in senile osteoporosis.

To evaluate the effects of calcium and 25-OHD in the therapy of senile osteoporosis, we studied a group of 39 women aged 69 +/- 7 (standard deviation, SD) years with severe osteoporosis. The group was characterized histomorphometrically by depressed bone remodeling rates without hyperosteoidosis. No subject had risk factors for osteopenia other than their age and postmenopausal status, and no subject was receiving therapy for bone disease at the onset of the study. Subjects were followed for 2 years after randomization to receive either 1200 mg/day of calcium (as calcium carbonate) and 40 micrograms/day of 25-OHD (calcium-25-OHD group), or 1200 mg/day of calcium plus placebo (calcium-placebo group). Calcium-25-OHD resulted in a clear increase in 25-OHD levels (p less than 0.001) and an increase in calcium absorption as indicated by urinary calcium excretion. Nevertheless, there was no significant change in fasting serum calcium, phosphorus, alkaline phosphatase, PTH, or 1,25-(OH)2D in either group. Radial and phalangeal bone mineral content and trabecular bone volume in the biopsied patients remained stable in both groups over the 2 year period. Unexpectedly, repeat bone biopsies revealed a clear improvement in the rate of mineralization in both groups, presumably as a result of the calcium supplementation alone. In summary, calcium-placebo and calcium-25-OHD treatment were both associated with stable appendicular bone mineral content in women with senile osteopenia. The finding of an effect of calcium supplementation on the rate of mineralization indicates that relative calcium deficiency may impair the mineralization phase of remodeling.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium and cholecalciferol: effects of small supplements in normal men.

The effect of small calcium and vitamin D supplements on mineral metabolism in normal persons is unclear. To investigate the biochemical response to these medications, we administered 1000 mg Ca and 25 micrograms cholecalciferol per day or a placebo to 92 normal men for 1 y. The Ca and cholecalciferol were tolerated well. 25-Hydroxycholecalciferol [25-(OH)D] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D] levels rose in treated subjects; there was no definite change in 1,25-(OH)2D concentrations. The average difference in 25-(OH)D levels between treated and untreated subjects was 30 nmol/L at 1 y. Fasting serum Ca, alkaline phosphatase, creatinine, and parathyroid hormone levels and the fasting urinary excretion of Ca, phosphorus and cAMP, were not affected. However, 24-h urinary Ca excretion was higher in the supplemented group (3.5 +/- 1.9 vs 4.7 +/- 1.7 mmol/d, p = 0.006). Serum P concentrations were slightly higher in the supplemented group at 1 y. In normal men small calcium and cholecalciferol supplements are safe, provide adequate vitamin D nutrition and apparently increase net gastrointestinal Ca absorption.