1,723 research outputs found
The prognostic importance of detecting mild sensory impairment in leprosy: A randomised controlled trial (TRIPOD 2)
No full textThis study was designed to investigate whether leprosy patients diagnosed with mild sensory impairment have a better prognosis when treated with steroids than similarly impaired patients treated with placebo. A multi-centre, randomized, double-blind, placebo-controlled trial was conducted in Nepal and Bangladesh. Patients were eligible if they had a confirmed leprosy diagnosis, were between 15 and 50 years old, had mild sensory impairment of the ulnar or posterior tibial nerve of less than 6 months duration and did not require steroids for other reasons. 'Mild impairment' was defined as 'impaired on the Semmes-Weinstein monofilament test, but testing normal on the ballpen sensory test'. Subjects were randomized to either prednisolone treatment starting at 40 mg per day, tapering over 4 months, or placebo. Nerve function was monitored monthly. Any patient who deteriorated was taken out of the trial and was put on full-dose steroid treatment. Outcome assessment was done at 4, 6, 9 and 12 months from the start of the treatment. Outcome measures were the proportion of patients needing full-dose prednisolone and the Semmes-Weinstein sum scores. Each patient contributed only one nerve to the analysis. Seventy-five patients had nerves eligible for analysis, of whom 41 (55%) and 34 (45%) were allocated to the prednisolone and placebo arms, respectively. At 4 months, three patients in the prednisolone arm (7%) and six in the placebo arm (18%) had an outcome event requiring full dose steroids. At 12 months, these proportions had almost reversed, 11 (27%) and 6 (18%) in the treatment and placebo arms, respectively. In the latter group, 75% had recovered spontaneously after 12 months. Prednisolone treatment of sensory impairment of the ulnar and posterior tibial nerves detectable with the monofilament test, but not with the ballpen test, did not improve the long-term outcome in terms of recovery of touch sensibility, not did it reduce the risk of leprosy reactions or nerve function impairment beyond the initial 4-month treatment phase. Two unexpected main findings were the strong tendency of mild sensory impairment to recover spontaneously and the fact that patients with mild sensory impairment without any other signs or symptoms of reaction or nerve function impairment are relatively rare
Treatment with corticosteroids of long-standing nerve function impairment in leprosy: a randomised control trial (TRIPOD 3)
No full textSome leprosy patients with long-standing nerve function impairment (NFI) appear to have responded favourably to treatment with corticosteroids. This study investigated whether patients with untreated NFI between 6 and 24 months duration and who are given standard regimen corticosteroid therapy, will have a better treatment outcome than a placebo group. A multicentre, randomized, double-blind placebo-controlled trial was conducted in Nepal and Bangladesh. Subjects were randomised to either prednisolone treatment starting at 40 mg/day, tapered by 5 mg every 2 weeks, and completed after 16 weeks, or placebo. Outcome assessments were at 4, 6, 9, and 12 months from the start of treatment. 92 MB patients on MDT were recruited, of whom 40 (45%) received prednisolone and 52 (55%) placebo treatment. No demonstrable additional improvement in nerve function, or in preventing further leprosy reaction events was seen in the prednisolone group. Overall, improvement of nerve function at 12 months was seen in about 50% of patients in both groups. Analysis of subgroups according to nerve (ulnar and posterior tibial), duration of NFI, and sensory and motor function, also did not reveal any differences between the treatment and placebo groups. There was however, indication of less deterioration of nerve function in the prednisolone group. Finally, there was no difference in the occurrence of adverse events between both groups. The trial confirms current practice not to treat long-standing NFI with prednisolone. Spontaneous recovery of nerve function appears to be a common phenomenon in leprosy. Leprosy reactions and new NFI occurred in a third of the study group, emphasizing the need to keep patients under regular surveillance during MDT, and, where possible, after completion of MDT
A clinical prediction rule for nerve function impairment in leprosy patients: revisited after 5 years of follow-up
No full textNerve function impairment (NFI) commonly occurs during or after chemotherapy in leprosy. We previously described a clinical predication rule to estimate the risk of NFI occurring within 2 years of diagnosis, based on 2510 patients who are followed up in the Bangladesh Acute Nerve Damage Study (BANDS). This prediction rule assigns new leprosy patients to one of three risk groups based on leprosy group and the presence or absence of NFI at registration. Updated data with up to 5 years of follow-up showed that 95% of all NFI occurred within 2 years. This study confirms the validity of the rule and supports the conclusion that there is little value for the detection of NFI in extending follow-up beyond 2 years
Delay in presentation, an indicator for nerve function status at registration and for treatment outcome: the experience of the Bangladesh Acute Nerve Damage Study cohort
No full textThe objective of our research was to relate delay in presentation in the Bangladesh Acute Nerve Damage Study cohort to intake status and to treatment outcome. The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study of 2664 consecutive newly registered patients at clinics run by the Danish-Bangladesh Mission Leprosy (DBLM) project in Nilphamari, northern Bangladesh. The 1-year intake began in April 1995. Three-year follow-up for PB cases and 5 years for MB cases was completed in 2001. Delay in presentation in the BANDS cohort is associated with increased signs of nerve function impairment at registration. Individuals presenting with no nerve impairment and maintaining nerve function to the end of follow-up had the shortest mean delays. Individuals presenting with impairment that did not improve during follow-up had the longest mean delays. Discussion focuses on the value of setting a threshold value defining early presentation. Since the WHO Grade 2 disability rate effectively sanctions lengthy delays where there is no impairment, an indicator relating directly to delay is preferred as an indicator for good practice in leprosy control
Incidence of acute nerve function impairment and reactions in leprosy: a prospective cohort analysis after 5 years of follow-up
No full textBackground Nerve function impairment (NFI) is the key outcome of the pathological processes of infection with Mycobacterium leprae, which can continue after completion of multidrug therapy (MDT) and lead to disability after leprosy patients are released from treatment. The objective of this study was to assess the need for and duration of surveillance of NFI.Methods Prospective cohort study of 2664 new leprosy patients in Bangladesh, with an observation period of 36 months in paucibacillary (PB) patients, and 60 monthsin multibacillary (MB) patients. Incidence rates (IR) were calculated with the number of patients developing NFI, type 1 and type 2 ractions, and silent neuritis for the first time after registration as the numerator, and cumulativeperson-years at risk (PYAR) as the denominator. Survival curves to the first event of NFI were also calculated.Results The IR of first event of NFI amongst MB patients was 16.1 per 100 PYAR, with121/357 (34%) developing NFI during the observation period. Of the 121 with a first event of NFI, 77 (64%) had this within a year after registration, 35 (29%) in the second year, and the remaining 9 (7%) after 2 years. The IR of first event of NFI amongst PB patients was 0.9 per 100 PYAR, with 54/2153 (2.5%) developing NFI during the observation period. Of the 54 with a first event of NFI, 48 (89%)had this within a year after registration, 3 (5.5%) in the second year, and the remaining 3 (5.5%) cases after 2 years. The percentage of PB patients with no NFIat registration surviving without developing NFI during the observation period was 99% and for PB patients with NFI at registration 92%. In MB patients without NFI at registration, the percentage surviving with no NFI during the observation period was 84% and for MB patients with NFI at registration only 36%.Conclusion New episodes of NFI and reactions after registration are common, in particular in MB patients with long-standing NFI at registration. The study highlights the importance of continuing surveillance for NFI of this risk group after registration for 2 years. Active surveillance beyond 2 years is not indicated
Adverse events of standardized regimens of corticosteroids for prophylaxis and treatment of nerve function impairment in leprosy: Results from the TRIPOD trials
No full textReactions in leprosy causing nerve function impairment (NFI) are increasingly treated with standardized regimens of corticosteroids, often under field conditions. Safety concerns led to an assessment of adverse events of corticosteroids, based on data of three trials studying prevention of NFI (the TRIPOD study). A multicentre, randomized, double-blind placebo-controlled trial was conducted in leprosy control programmes in Nepal and Bangladesh. Treatment was with prednisolone according to fixed schedules for 16 weeks, starting in one trial with 20 mg/day (prophylactic regimen: total dosage 1.96 g) and in the other two trials with 40 mg/day (therapeutic regimen: total dosage 2.52 g). Minor adverse events were defined as moon face, fungal infections, acne, and gastric pain requiring antacid. Major adverse events were defined as psychosis, peptic ulcer, glaucoma, cataract, diabetes and hypertension. Also, the occurrence of infected plantar, palmar, and corneal ulceration was monitored, together with occurrence of TB. Considering all three trials together, minor adverse events were observed in 130/815 patients (16%). Of these, 51/414 (12%) were in the placebo group and 79/401 (20%) in the prednisolone group. The relative risk for minor adverse events in the prednisolone group was 1.6 (P = 0.004). Adverse events with a significantly increased risk were acne, fungal infections and gastric pain. Major adverse events were observed in 15/815 patients (2%); 7/414 (2%) in the placebo group and 8/401 (2%) in the prednisolone group. No major adverse events had a significantly increased risk in the prednisolone arm of the trials. No cases of TB were observed in 300 patients who could be followed-up for 24 months. Standardized regimens of corticosteroids for both prophylaxis and treatment of reactions and NFI in leprosy under field conditions in developing countries are safe when a standard pre-treatment examination is performed, treatment for minor conditions can be carried out by field staff, referral for specialized medical care is possible, and sufficient follow-up is done during and after treatment
Budget
No full textEr is een groeiend besef dat bouwprocesinnovatie een belangrijke bijdrage kan leveren aan de verbetering en versterking van de bouwbedrijfskolom als geheel. Op verschillende niveaus wordt in alle bedrijfstakken, dus ook in de bouw, de toenemende concurrentie ervaren en dus de urgentie gevoeld om sneller in te spelen op versterking van de vraagkant van de markt. De verschuiving van een meer productgerichte naar een procesgerichte invalshoek van het bouwen, leidt tot de opgave om de verschillende procesfasen en de daarin opererende partijen beter op elkaar af te stemmen. Kennis van bouw- en uitvoeringstechnologie, onderhoud en beheer moet in een zo vroeg mogelijke fase een rol spelen in de ontwikkeling van een project. Het besef dat er beter samengewerkt moet worden, wordt "bouwbreed" gedeeld. Dit vereist echter een substantiële verbetering van het ontwerp- en bouwproces en daarvoor is specifieke kennis, kennisbeheer en toegankelijkheid van die kennis nodig. Deze publicatie wil een bijdrage leveren aan de vernieuwing en verbetering van het bouwproces door de aandacht te richten op een voor Nederlandse begrippen vrij nieuwe vorm van samenwerking: de projectalliantie.Real Estate & HousingArchitecture and The Built Environmen
A new economic instrument for financing accelerated landfill aftercare
No full textThe key aspects of landfill operation that remain unresolved are the extended timescale and uncertain funding of the post-closure period. This paper reviews the topic and proposes an economic instrument to resolve the unsustainable nature of the current situation. Unsustainability arises from the sluggish degradation of organic material and also the slow flushing of potential pollutants that is exacerbated by low-permeability capping. A landfill tax or aftercare provision rebate is proposed as an economic instrument to encourage operators to actively advance the stabilization of landfilled waste. The rebate could be accommodated within existing regulatory and tax regimes and would be paid for: (i) every tonne of nitrogen (or other agreed leachate marker) whose removal is advanced via the accelerated production and extraction of leachate; (ii) every tonne of non-commercially viable carbon removed via landfill gas collection and treatment. The rebates would be set at a level that would make it financially attractive to operators and would encourage measures such as leachate recirculation, in situ aeration, and enhanced flushing. Illustrative calculations suggest that a maximum rebate of up to ~€50/tonne MSW would provide an adequate incentive
Steroid prophylaxis for prevention of nerve function impairment in leprosy: randomised placebo controlled trial (TRIPOD1)
No full textObjective:
To determine whether addition of low dose prednisolone to multidrug treatment can prevent reaction and nerve function impairment in leprosy. Design:
Multicentre, double blind, randomised, placebo controlled, parallel group trial. Setting:
Six centres in Bangladesh and Nepal. Participants:
636 people with newly diagnosed multibacillary leprosy. Intervention:
Prednisolone 20 mg/day for three months, with tapering dose in month 4, plus multidrug treatment, compared with multidrug treatment alone. Main outcome measures:
Signs of reaction, impairment of sensory and motor nerve function, and nerve tenderness needing full dose prednisolone at four months and one year. Results:
Prednisolone had a significant effect in the prevention of reaction and nerve function impairment at four months (relative risk 3.9, 95% confidence interval 2.1 to 7.3), but this was not maintained at one year (relative risk 1.3, 0.9 to 1.8). Fewer events occurred in the prednisolone group at all time points up to 12 months, but the difference at 12 months was small. Subgroup analysis showed a difference in response between people with and without impairment of nerve function at diagnosis. Conclusions:
The use of low dose prophylactic prednisolone during the first four months of multidrug treatment for leprosy reduces the incidence of new reactions and nerve function impairment in the short term, but the effect is not sustained at one year. The presence of nerve function impairment at diagnosis may influence the response to low dose prednisolone
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