P.G. Nicholls

The Participation Scale: measuring a key concept in public health.

Purpose. To develop a scale to measure (social) participation for use in rehabilitation, stigma reduction and social integration programmes. Method. A scale development study was carried out in Nepal, India and Brazil using standard methods. The instrument was to be based on the Participation domains of the International Classification of Functioning, Disability and Health (ICF), be cross-cultural in nature and assess client-perceived participation. Respondents rated their participation in comparison with a ‘peer’, defined as ‘someone similar to the respondent in all respects except for the disease or disability’. Results. An 18-item instrument was developed in seven languages. Crohnbachs α was 0.92, intra-tester stability 0.83 and inter-tester reliability 0.80. Discrimination between controls and clients was good at a Participation Score threshold of 12. Responsiveness after a ‘life change’ was according to expectation. Conclusions. The Participation Scale is reliable and valid to measure client-perceived participation in people affected by leprosy or disability. It is expected to be valid in other (stigmatised) conditions also, but this needs confirmation. The scale allows collection of participation data and impact assessment of interventions to improve social participation. Such data may be compared between clients, interventions and programmes. The scale is suitable for use in institutions, but also at the peripheral level.

A clinical prediction rule for nerve-function impairment in leprosy patients

BACKGROUND Nerve-function impairment (NFI) commonly occurs during or after chemotherapy in leprosy and is the key pathological process leading to disability and handicap. We describe the development of a simple clinical prediction rule for estimating the risk of NFI occurrence. METHODS New leprosy cases who presented to a centre in Bangladesh were recruited and followed up for 2 years in a field setting. We used multivariable regression analysis by Coxs proportional hazards model to identify predictive variables for NFI. Discriminative ability was measured by a concordance statistic. Internal validity was assessed with bootstrap resampling techniques. FINDINGS 2510 patients were followed up for 2 years, 166 developed NFI. A simple model was developed with leprosy group (either paucibacillary leprosy [PB] or multibacillary leprosy [MB]) and the presence of any nerve-function loss at registration as predictive variables. Patients with PB leprosy and no nerve-function loss had a 1.3% (95% CI 0.8-1.8%) risk of developing NFI within 2 years of registration; patients with PB leprosy and nerve-function loss, or patients with MB leprosy and no nerve-function loss had a 16.0% (12-20%) risk; and patients with MB leprosy with nerve-function loss had a 65% (56-73%) risk. INTERPRETATION Our prediction rule can be used to plan surveillance of new leprosy patients. Patients at low risk of NFI may need no follow-up beyond their course of chemotherapy (6 months); patients with intermediate risk need a minimum of 1 year of surveillance; and patients with high risk should have at least 2 years of surveillance for new NFI. Current recommendations for surveillance of patients with leprosy (for the duration of chemotherapy only) exclude an important group of patients who are at risk of developing NFI after completion of treatment.

Early Diagnosis of Neuropathy in Leprosy—Comparing Diagnostic Tests in a Large Prospective Study (the INFIR Cohort Study)

Background Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest. Methods and Findings One hundred and eighty-eight multibacillary (MB) leprosy patients were selected from a cohort of 303 and followed for 2 years after diagnosis. Nerve function was evaluated at each visit using nerve conduction (NC), quantitative thermal sensory testing and vibrometry, dynamometry, monofilament testing (MFT), and voluntary muscle testing (VMT). Study outcomes were sensory and motor impairment detected by MFT or VMT. Seventy-four of 188 patients (39%) had a reaction, neuritis, or new nerve function impairment (NFI) event during a 2-year follow-up. Sub-clinical neuropathy was extensive (20%–50%), even in patients who did not develop an outcome event. Sensory nerve action potential (SNAP) amplitudes, compound motor action potential (CMAP) velocities, and warm detection thresholds (WDT) were most frequently affected, with SNAP impairment frequencies ranging from 30% (median) to 69% (sural). Velocity was impaired in up to 43% of motor nerves. WDTs were more frequently affected than cold detection thresholds (29% versus 13%, ulnar nerve). Impairment of SNC and warm perception often preceded deterioration in MF or VMT scores by 12 weeks or more. Conclusions A large proportion of leprosy patients have subclinical neuropathy that was not evident when only MFT and VMT were used. SNC was the most frequently and earliest affected test, closely followed by WDT. They are promising tests for improving early detection of neuropathy, as they often became abnormal 12 weeks or more before an abnormal monofilament test. Changes in MFT and VMT score mirrored changes in neurophysiology, confirming their validity as screening tests.

Steroid prophylaxis for prevention of nerve function impairment in leprosy: randomised placebo controlled trial (TRIPOD 1).

Abstract Objective 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.

Nerve function impairment in leprosy: design, methodology, and intake status of a prospective cohort study of 2664 new leprosy cases in Bangladesh (The Bangladesh Acute Nerve Damage Study).

The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study designed to investigate epidemiological, diagnostic, therapeutic and operational aspects of acute nerve function impairment in leprosy. The study is based at a single centre in Bangladesh, in an area with a high prevalence of leprosy. The centre, Danish Bangladesh Leprosy Mission, has a well-established vertical leprosy control programme. In this paper, the study design and methodology are described, together with definitions of nerve function impairment (NFI) used in this and subsequent papers. The study recruited 2664 new leprosy cases in a 12-month period. The male:female ratio is 1.25:1, and 17.61% of the cohort are under 15 years of age. In all, 83.33% of the cohort are paucibacillary (PB), and 16.67% multibacillary (MB). However, the MB rate amongst males is 19.72%, and amongst females is 12.85%, despite an equal period of delay to diagnosis. 55% of patients presented for treatment within 12 months of developing symptoms 6.12% of the total number of cases were smear positive, and 36.71% of the MB cases were smear positive. 9.61% of the total number of cases were graded as having World Health Organisation (WHO) disability grade 1, and 5.97% had grade 2. Amongst MB cases, 27.48% had WHO grade 1 disability present, and 18.24% had grade 2 present, compared with 6.04% and 3.51%, respectively, amongst PB cases. A total of 11.90% of the cohort had sensory NFI of any kind, and 7.39% had motor NFI. Ninety patients presented with NFI needing treatment (3.38%), and of these, 61 (67.78%) had silent NFI. MB patients had a prevalence of reaction/NFI needing treatment nearly 7 times higher than PB cases (15.32% amongst MB; 2.30% amongst PB), and males nearly double that of females (5.67% amongst males, 2.96% amongst females). The most commonly affected nerve by function impairment was the posterior tibial (sensory) with 6.46% of nerves affected (9.38% of patients), followed by the ulnar nerve with 3.23% of nerves impaired (5.56% of patients). Future research and publications, building on this foundation, will focus on the following areas: the incidence of NFI and reactive events, the risk factors for developing NFI, and the response to treatment of patients developing acute NFI.

Cytokine and Protein Markers of Leprosy Reactions in Skin and Nerves: Baseline Results for the North Indian INFIR Cohort

Background Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions. Methodology/Principal Findings TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100. Conclusions/Significance Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R.

The histological diagnosis of leprosy type 1 reactions: identification of key variables and an analysis of the process of histological diagnosis

Background: Type 1 leprosy reactions (T1R) are a major inflammatory complication of leprosy affecting 30% of patients with borderline leprosy, but there has been no diagnostic evaluation of the histological diagnosis of this entity. Methods: In a prospective study based in India, skin biopsies were taken from 99 patients with clinically diagnosed T1R and 52 non-reactional controls. These were assessed histologically by four histopathologists whose assessments were then compared. Results: Reactions were under-diagnosed, with 32–62% of clinically diagnosed reactions being given a histological diagnosis. The pathologists showed good specificities (range 72% to 93%) but much poorer sensitivities (range 42% to 78%). The most commonly reported histological features of TIR were cell maturity, oedema and giant cells. Five key variables were identified that the pathologists used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant cell numbers, dermal oedema and HLA-DR expression. A predictive model for the diagnosis of T1R was developed using stepwise logistic regression analysis, with clinical diagnosis of reaction as an outcome, and then identification of the key variables that each pathologist used in making the diagnosis of T1R. 34–53% of the variation between pathologists could be accounted for. The four pathologists used a similar diagnostic model and for all of them their estimations of epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma fraction were significant variables in the diagnosis of T1R. Each pathologist then added in variables that were specific to themselves. Conclusions: This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions.

Are nurse and pharmacist independent prescribers making clinically appropriate prescribing decisions? An analysis of consultations

Objectives: Legislation and health policy enabling nurses and pharmacists to prescribe a comprehensive range of medicines has been in place in the UK since 2006. Our objective was to evaluate the clinical appropriateness of prescribing by these professionals. Methods: A modified version of the Medication Appropriateness Index (MAI) was used by 10 medical, seven pharmacist and three nurse independent raters to evaluate a sample of 100 audio-recorded consultations in which a medicine was prescribed by a nurse or pharmacist. Raters were current prescribers with recognized experience in prescribing. Consultations were recorded in nine clinical practice settings in England. Results: Raters’ analysis indicated that, in the majority of instances, nurses and pharmacists were prescribing clinically appropriately on all of the ten MAI criteria (indication, effectiveness, dosage, directions, practicality, drug-drug interaction, drug-disease interaction, duplication, duration, cost). Highest mean ‘inappropriate’ ratings were given for correct directions (nurses 12%; pharmacists 11%) and the cost of the drug prescribed (nurses 16% pharmacists 22%). Analysis of raters’ qualitative comments identified two main themes: positive views on the overall safety and effectiveness of prescribing episodes; and potential for improvement in nurses’ and pharmacists’ history-taking, assessment and diagnosis skills. Cnclusions: Nurses and pharmacists are generally making clinically appropriate prescribing decisions. Decisions about the cost of drugs prescribed and assessment and diagnostic skills are areas for quality improvement.

Features and outcomes of unplanned hospital admissions of older people due to ill-defined (R-coded) conditions: Retrospective analysis of hospital admissions data in England

BackgroundRising rates of unplanned admissions among older people are placing unprecedented demand on health services internationally. Unplanned hospital admissions for ill-defined conditions (coded with an R prefix within Chapter XVIII of the International Classification of Diseases-10) have been targeted for admission avoidance strategies, but little is known about these admissions. The aim of this study was to determine the incidence and factors predicting ill-defined (R-coded) hospital admissions of older people and their association with health outcomes.MethodsRetrospective analysis of unplanned hospital admissions to general internal and geriatric medicine wards in one hospital over 12 months (2002) with follow-up for 36 months. The study was carried out in an acute teaching hospital in England. The participants were all people aged 65 and over with unplanned hospital admissions to general internal and geriatric medicine. Independent variables included time of admission, residence at admission, route of admission to hospital, age, gender, comorbidity measured by count of diagnoses. Main outcome measures were primary diagnosis (ill-defined versus other diagnostic code), death during the hospital stay, deaths to 36 months, readmissions within 36 months, discharge destination and length of hospital stay.ResultsIncidence of R-codes at discharge was 21.6%, but was higher in general internal than geriatric medicine (25.6% v 14.1% respectively). Age, gender and co-morbidity were not significant predictors of R-code diagnoses. Admission via the emergency department (ED), out of normal general practitioner (GP) hours, under the care of general medicine and from non-residential care settings increased the risk of receiving R-codes. R-coded patients had a significantly shorter length of stay (5.91 days difference, 95% CI 4.47, 7.35), were less likely to die (hazard ratio 0.71, 95%CI 0.59, 0.85) at any point, but were as likely to be readmitted as other patients (hazard ratio 0.96 (95% CI 0.88, 1.05).ConclusionsR-coded diagnoses accounted for 1/5 of emergency admission episodes, higher than anticipated from total English hospital admissions, but comparable with rates reported in similar settings in other countries. Unexpectedly, age did not predict R-coded diagnosis at discharge. Lower mortality and length of stay support the view that these are avoidable admissions, but readmission rates particularly for further R-coded admissions indicate on-going health care needs. Patient characteristics did not predict R-coding, but organisational features, particularly admission via the ED, out of normal GP hours and via general internal medicine, were important and may offer opportunity for admission reduction strategies.

Predicting neuropathy and reactions in leprosy at diagnosis and before incident events-results from the INFIR cohort study

Background Leprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions. Methodology/Principal Findings The study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event. Conclusions/Significance These findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability.