An Apple a Day to Keep the Parkinson's Disease Doctor Away?

It is challenging to reliably assess the motor features of Parkinson's disease in real-time. This has motivated the search for new digital outcomes that can objectively and remotely measure the severity of parkinsonian motor impairments over an extended period of time. The United States Food and Drug Administration (FDA) has recently granted a 510(k) clearance to the Rune Labs Kinematics System, an ambulatory, smartwatch-based monitoring system to remotely track tremor and dyskinesias in persons with Parkinson's disease. The FDA clearance means that this new digital approach can be regarded as being safe for use in daily practice, with acceptable correlations to clinically based measures. However, the immediate implications for clinicians are limited, because it remains to be demonstrated whether the digital signals correlate well to clinically meaningful outcomes at patient level. The impact on research is also restricted for now, as more validation studies are needed before this new digital approach can be used as primary or secondary endpoint in clinical trials. ANN NEUROL 2023;93:681-685.

Normal threshold values for a monofilament sensory test in sural and radial cutaneous nerves in Indian and Nepali volunteers.

The monofilament test (MFT) is a reliable method to assess sensory nerve function in leprosy and other neuropathies. Assessment of the radial cutaneous and sural nerves, in addition to nerves usually tested, can help improve diagnosis and monitoring of nerve function impairment (NFI). To enable the detection of impairments in leprosy patients, it is essential to know the monofilament threshold of these two nerves in normal subjects. The radial cutaneous, sural, ulnar, median and posterior tibial nerves of 245 volunteers were tested. All nerves were tested at three sites on both left and right sides. Normal monofilament thresholds were calculated per test-site and per nerve. We assessed 490 radial cutaneous and 482 sural nerves. The normal monofilament was 2 g (Filament Index Number (FIN) 4.31) for the radial cutaneous and 4 g (FIN 4.56) for the sural nerve, although heavy manual laborers demonstrated a threshold of 10 g (FIN 5.07) for the sural nerve. For median and ulnar nerves, the 200 mg (FIN 3.61) filament was confirmed as normal while the 4 g (FIN 4.56) filament was normal for the posterior tibial. Age and occupation have an effect on the mean touch sensitivity but do not affect the normal threshold for the radial cutaneous and sural nerves. The normal thresholds for the radial cutaneous and sural nerves are determined as the 2 g (FIN 4.31) and the 4 g (FIN 4.56) filaments, respectively. The addition of the radial cutaneous and sural nerve to sensory nerve assessment may improve the diagnosis of patients with impaired sensory nerve function.

Reliability of clinical nerve function assessment in peripheral neuropathies.

INTRODUCTION: Sensory and/or motor nerve function impairment as a consequence of neuropathy is often assessed using electroneurophysiological tests. However, in low-resource countries where the required equipment is rarely available, manual muscle strength testing (MMST) and monofilament testing (MFT) offer very reliable alternatives. In six leprosy programmes in four Asian countries, a multi-centre randomised clinical trial (RCT) was carried out to assess the effect of corticosteroids on neuropathy in leprosy-affected people. The sensory and motor nerve function was tested using MMST and MFT, including new test sites for the sural and radial cutaneous nerves (MFT) and the posterior tibial and common peroneal nerves (MMST). The reliability studies of the MMST and MFT tests of the TENLEP (Treatment of Early Neuropathy in LEProsy) trials are presented here. METHODS: Two assessors in each centre independently used the MFT and MMST in 30 leprosy-affected people. RESULTS: Reliability is good to very good for MFT in nearly all nerves. MMST also shows good to very good agreement, with a few exceptions. CONCLUSION: Our study confirms that MMST and MFT can be performed reliably, and that the new tests also have acceptable reliability.

Combining peer-led self-care interventions for people affected by leprosy or diabetes in leprosy-endemic countries. What do health care professionals think?

INTRODUCTION: Leprosy is slowly decreasing in incidence whereas diabetes is a growing health concern. Despite differences in aetiology, both diseases may lead to peripheral neuropathy and subsequent injuries and permanent impairments. There are also indications of similarities in psychosocial consequences. Prevention of Disability (POD) and self-management are often recommended for both diseases. This led to the idea of exploring the feasibility of combined peer-led self-care interventions for people with these disorders. OBJECTIVE: To explore the opinions of health care professionals about combining peer-led self-care interventions for people affected by leprosy or diabetes in leprosy-endemic countries. METHOD: An exploratory study was conducted to collect quantitative data by means of an e-questionnaire and qualitative data through in-depth semi-structured interviews with key informants. RESULTS: In total, 227 respondents answered the e-questionnaire and 22 in-depth interviews were conducted. Resemblances in physical complications between leprosy and diabetes were confirmed by the respondents. Psychosocial similarities included limitations in daily activity and in social participation, but stigma in leprosy was thought to be an important difference. Considerable overlap in current practices was found, mainly in patient education in POD, skin assessment and skin care, and the recommendation to use protective footwear. Knowledge exchange between leprosy and diabetes specialists is limited, although combined interventions were reported. The majority of respondents think that combined interventions are 'possible' (33.3%) or 'possible and promising' (30.8%). Professionals working with both diseases are more positive than those working with leprosy or diabetes only. The greatest barriers for combined interventions are perceived to be leprosy-related stigma, differences in underlying socio-economic status, attitudes of health care professionals and the current organization of health care systems. CONCLUSIONS: Responses indicate perspectives for combined interventions for the prevention of disabilities. For this, it is essential to intensify knowledge exchange between leprosy and diabetes professionals, to overcome barriers and to secure government policy support. Opportunities should be assessed in a situation-specific way.

Two randomized controlled clinical trials to study the effectiveness of prednisolone treatment in preventing and restoring clinical nerve function loss in leprosy: the TENLEP study protocols.

BACKGROUND: Nerve damage in leprosy often causes disabilities and deformities. Prednisolone is used to treat nerve function impairment (NFI). However, optimal dose and duration of prednisolone treatment has not been established yet. Besides treating existing NFI it would be desirable to prevent NFI. Studies show that before NFI is clinically detectable, nerves often show subclinical damage. Within the 'Treatment of Early Neuropathy in LEProsy' (TENLEP) study two double blind randomized controlled trials (RCT) will be carried out: a trial to establish whether prednisolone treatment of 32 weeks duration is more effective than 20 weeks in restoring nerve function in leprosy patients with clinical NFI (Clinical trial) and a trial to determine whether prednisolone treatment of early sub-clinical NFI can prevent clinical NFI (Subclinical trial). METHODS: Two RCTs with a follow up of 18 months will be conducted in six centers in Asia. In the Clinical trial leprosy patients with recent (< 6 months) clinical NFI, as determined by Monofilament Test and Voluntary Muscle Test, are included. The primary outcomes are the proportion of patients with restored or improved nerve function. In the Subclinical trial leprosy patients with subclinical neuropathy, as determined by Nerve Conduction Studies (NCS) and/or Warm Detection Threshold (WDT), and without any clinical signs of NFI are randomly allocated to a placebo group or treatment group receiving 20 weeks prednisolone. The primary outcome is the proportion of patients developing clinical NFI. Reliability and normative studies are carried out before the start of the trial. DISCUSSION: This study is the first RCT testing a prednisolone regimen with a duration longer than 24 weeks. Also it is the first RCT assessing the effect of prednisolone in the prevention of clinical NFI in patients with established subclinical neuropathy. The TENLEP study will add to the current understanding of neuropathy due to leprosy and provide insight in the effectiveness of prednisolone on the prevention and recovery of NFI in leprosy patients. In this paper we present the research protocols for both Clinical and Subclinical trials and discuss the possible findings and implications. TRIAL REGISTRATION: Netherlands Trial Register: NTR2300 Clinical Trial Registry India: CTRI/2011/09/002022.

Design of a District-level Pilot Project Model for the Prevention and Care of Chronic Wounds and Lymphedema in Settings With Limited Resources .

 Chronic wounds and lymphedema are often secondary complications of chronic diseases. Chronic wounds and lymphedema cut across diseases, settings, and borders especially in settings with limited resources, and present an opportunity to implement an integrated approach to prevention and care. The following article describes key elements in the design and development of pilot projects based on the principles of the World Health Organization's (WHO) Innovative Care for Chronic Conditions model. The pilot projects will advance the efforts of World Alliance for Wound and Lymphedema Care (WAWLC) to aid health systems in building capacity for effective wound and lymphedema care. .

High genetic diversity among Mycobacterium tuberculosis complex strains from Sierra Leone.

BACKGROUND: Among tuberculosis (TB) high incidence regions, Sub-Saharan Africa is particularly affected with approx. 1.6 million new cases every year. Besides this dramatic situation, data on the diversity of Mycobacterium tuberculosis complex (MTBC) strains causing this epidemic in this area are only sparsely available. Here we analyzed the population structure of strains from Sierra Leone with a special focus on the prevalence of M. africanum. RESULTS: A total of 97 strains isolated from smear positive cases registered for re-treatment in the Western Area and Kenema districts in years 2003/2004 were investigated by susceptibility testing (first line drugs) and molecular typing (IS6110 fingerprinting, spoligotyping, and MIRU-VNTR typing). Among the strains analyzed, 32 were resistant to isoniazid, and 11 were multidrug resistant (at least resistant to isoniazid and rifampin). The population diversity was high with two previously described M. africanum lineages (West African-1, n = 6; West African-2, n = 17) and seven M. tuberculosis lineages (Haarlem, n = 14; LAM, n = 15; EAI, n = 4; Beijing, n = 4; S-type, n = 4, X-type, n = 1; Cameroon, n = 4). Furthermore, two new M. tuberculosis genotypes Sierra Leone-1 (n = 7) and -2 (n = 10) were found. Strain classification according to a 7 bp deletion in pks1/15 revealed that the majority of M. tuberculosis strains belonged to the Euro American lineage (66 out of 74). CONCLUSION: Resistance rates in Sierra Leone have reached an alarming level. The population structure of MTBC strains shows an intriguing diversity raising the question of possible consequences for TB epidemic and for the introduction of new diagnostic tests or treatment strategies in West Africa.

The Development of a Mobile Application to Support Peripheral Health Workers to Diagnose and Treat People with Skin Diseases in Resource-Poor Settings.

The high prevalence of skin diseases in resource-poor settings, where health workers with sufficient knowledge of skin diseases are scarce, calls for innovative measures. Timely diagnosis and treatment of skin diseases, especially neglected tropical diseases (NTDs) that manifest with skin lesions, such as leprosy, is crucial to prevent disabilities as well as psychological and socioeconomic problems. Innovative technological methods like telemedicine and mobile health (mHealth) can help to bridge the gap between the burden of skin diseases and the lack of capable staff in resource-poor settings by bringing essential health services from central level closer to peripheral levels. Netherlands Leprosy Relief (NLR) has developed a mobile phone application called the 'SkinApp', which aims to support peripheral health workers to recognize the early signs and symptoms of skin diseases, including skin NTDs, and to start treatment promptly or refer for more advanced diagnostic testing or disease management when needed. Further research is needed to determine how greatly mHealth in general and the SkinApp in particular can contribute to improved health outcomes, efficiency, and cost-effectiveness.

Early detection of neuropathy in leprosy: a comparison of five tests for field settings.

BACKGROUND: Early detection and treatment of neuropathy in leprosy is important to prevent disabilities. A recent study showed that the Nerve Conduction Studies (NCS) and Warm Detection Thresholds (WDT) tests can detect leprosy neuropathy the earliest. These two tests are not practical under field conditions, however, because they require climate-controlled rooms and highly trained staff and are expensive. We assessed the usefulness of alternative test methods and their sensitivity and specificity to detect neuropathy at an early stage. METHODS: Through a literature search we identified five alternative devices that appeared user-friendly, more affordable, portable and/or battery-operated: the Neuropad®, Vibratip™, NC-Stat®DPNCheck™, NeuroQuick and the Thermal Sensibility Tester (TST), assessing respectively sweat function, vibration sensation, nerve conduction, cold sensation and warm sensation. In leprosy patients in Bangladesh, the posterior tibial and sural nerves that tested normal for the monofilament test and voluntary muscle test were assessed with the NCS and WDT as reference standard tests. The alternative devices were then tested on 94 nerves with abnormal WDT and/or NCS results and on 94 unaffected nerves. Sensitivity and specificity were the main outcomes. RESULTS: The NeuroQuick and the TST showed very good sensitivity and specificity. On the sural nerve, the NeuroQuick had both a sensitivity and a specificity of 86%. The TST had a sensitivity of 83% and a specificity of 82%. Both the NC-Stat®DPNCheck™ and Vibratip™ had a high specificity (88% and 100%), but a low sensitivity (16% and 0%). On the posterior tibial nerve, the NeuroQuick and the TST also showed good sensitivity, but the sensitivity was lower than for the sural nerve. The Neuropad® had a sensitivity of 56% and a specificity of 61%. CONCLUSIONS: The NeuroQuick and TST are good candidates for further field-testing for reliability and reproducibility. The feasibility of production on a larger scale should be examined.

Effectiveness of 32 versus 20 weeks of prednisolone in leprosy patients with recent nerve function impairment: A randomized controlled trial.

BACKGROUND: While prednisolone is commonly used to treat recent nerve function impairment (NFI) in leprosy patients, the optimal treatment duration has not yet been established. In this "Treatment of Early Neuropathy in Leprosy" (TENLEP) trial, we evaluated whether a 32-week prednisolone course is more effective than a 20-week course in restoring and improving nerve function. METHODS: In this multi-centre, triple-blind, randomized controlled trial, leprosy patients who had recently developed clinical NFI (<6 months) were allocated to a prednisolone treatment regimen of either 20 weeks or 32 weeks. Prednisolone was started at either 45 or 60 mg/day, depending on the patient's body weight, and was then tapered. Throughout follow up, NFI was assessed by voluntary muscle testing and monofilament testing. The primary outcome was the proportion of patients with improved or restored nerve function at week 78. As secondary outcomes, we analysed improvements between baseline and week 78 on the Reaction Severity Scale, the SALSA Scale and the Participation Scale. Serious Adverse Events and the need for additional prednisolone treatment were monitored and reported. RESULTS: We included 868 patients in the study, 429 in the 20-week arm and 439 in the 32-week arm. At 78 weeks, the proportion of patients with improved or restored nerve function did not differ significantly between the groups: 78.1% in the 20-week arm and 77.5% in the 32-week arm (p = 0.821). Nor were there any differences in secondary outcomes, except for a significant higher proportion of Serious Adverse Events in the longer treatment arm. CONCLUSION: In our study, a 20-week course of prednisolone was as effective as a 32-week course in improving and restoring recent clinical NFI in leprosy patients. Twenty weeks is therefore the preferred initial treatment duration for leprosy neuropathy, after which likely only a minority of patients require further individualized treatment.

First-line health care provider performance in the management of common skin diseases using an algorithmic approach as a diagnostic tool in Kano State, Nigeria.

Skin diseases are common worldwide, though prevalence rates in rural areas are difficult to estimate, and are primarily based on hospital studies rather than community-based studies. Primary health care providers in rural areas often lack sufficient knowledge about skin diseases, which contributes to poor skin management and subsequently causes considerable morbidity. This study looked at the performance of first-line health care providers in the management of common skin disease, using an algorithmic approach with a flowchart with diagnostic steps. As a reference standard, two dermatologists independently validated the diagnoses and treatment choices made by the providers. The performance of the algorithm was calculated in terms of the sensitivity, specificity, positive predictive value (PPV), and negative predictive value for each skin disease of the algorithm. A total of 19 patent medicine vendors and 12 traditional healers from Kano State in Nigeria diagnosed 4,147 patients with suspected skin symptoms. The most common skin disease was tinea capitis (59.2%), and it was found predominantly among boys below 15 years of age. Together, patent medicine vendors and traditional healers had 82% of the cases correctly diagnosed, and in 82% they prescribed the correct treatment. The sensitivities varied for each skin disease from 94.8% for tinea capitis to 7.1% for contact dermatitis. The specificities varied between 87.0% and 98.6%. Except for tinea capitis, lower PPVs were found for the various skin diseases when compared to earlier studies. In spite of the observed low sensitivities and low PPVs for several diseases, the algorithm seems to offer an improvement in management of common skin diseases at the peripheral level. With adaptations in training, further refinement of the algorithm and refresher training, predictive values and sensitivities can be increased.

A systematic review on the epidemiological data of erythema nodosum leprosum, a type 2 leprosy reaction.

BACKGROUND: Erythema Nodosum Leprosum (ENL) is a humoral immunological response in leprosy that leads to inflammatory skin nodules which may result in nerve and organ damage, and may occur years after antibiotic treatment. Multiple episodes are frequent and suppression requires high doses of immunosuppressive drugs. Global occurrence is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Systematic review of evidence on ENL incidence resulted in 65 papers, predominantly from India (24) and Brazil (9), and inclusive of four reviews. Average incidences are based on cumulative incidence and size of study populations (n>100). In field-based studies 653/54,737 (1.2%) of all leprosy cases, 194/4,279 (4.5%) of MB cases, and 86/560 (15.4%) of LL cases develop ENL. Some studies found a range of 1-8 per 100 person-years-at-risk (PYAR) amongst MB cases. Hospital samples indicate that 2,393/17,513 (13.7%) of MB cases develop ENL. Regional differences could not be confirmed. Multiple ENL episodes occurred in 39 to 77% of ENL patients, with an average of 2.6. Some studies find a peak in ENL incidence in the first year of treatment, others during the second and third year after starting MDT. The main risk factor for ENL is a high bacteriological index. CONCLUSIONS/SIGNIFICANCE: Few studies reported on ENL as a primary outcome, and definitions of ENL differed between studies. Although, in this review averages are presented, accurate data on global and regional ENL incidence is lacking. Large prospective studies or accurate surveillance data would be required to clarify this. Health staff needs to be aware of late reactions, as new ENL may develop as late as five years after MDT completion, and recurrences up to 8 years afterwards.

Cost-effectiveness analysis of three leprosy case detection methods in Northern Nigeria.

BACKGROUND: Despite several leprosy control measures in Nigeria, child proportion and disability grade 2 cases remain high while new cases have not significantly reduced, suggesting continuous spread of the disease. Hence, there is the need to review detection methods to enhance identification of early cases for effective control and prevention of permanent disability. This study evaluated the cost-effectiveness of three leprosy case detection methods in Northern Nigeria to identify the most cost-effective approach for detection of leprosy. METHODS: A cross-sectional study was carried out to evaluate the additional benefits of using several case detection methods in addition to routine practice in two north-eastern states of Nigeria. Primary and secondary data were collected from routine practice records and the Nigerian Tuberculosis and Leprosy Control Programme of 2009. The methods evaluated were Rapid Village Survey (RVS), Household Contact Examination (HCE) and Traditional Healers incentive method (TH). Effectiveness was measured as number of new leprosy cases detected and cost-effectiveness was expressed as cost per case detected. Costs were measured from both providers' and patients' perspectives. Additional costs and effects of each method were estimated by comparing each method against routine practise and expressed as incremental cost-effectiveness ratio (ICER). All costs were converted to the U.S. dollar at the 2010 exchange rate. Univariate sensitivity analysis was used to evaluate uncertainties around the ICER. RESULTS: The ICER for HCE was $142 per additional case detected at all contact levels and it was the most cost-effective method. At ICER of $194 per additional case detected, THs method detected more cases at a lower cost than the RVS, which was not cost-effective at $313 per additional case detected. Sensitivity analysis showed that varying the proportion of shared costs and subsistent wage for valuing unpaid time did not significantly change the results. CONCLUSION: Complementing routine practice with household contact examination is the most cost-effective approach to identify new leprosy cases and we recommend that, depending on acceptability and feasibility, this intervention is introduced for improved case detection in Northern Nigeria.

Barriers to care seeking in directly observed therapy short-course (DOTS) clinics and tuberculosis control in southern Nigeria: a qualitative analysis.

An understanding of the socioeconomic and cultural realities of persons infected with tuberculosis (TB) in communities is important to re-strategizing control programs because these realities often come as constraints to the use of the directly observed therapy short-course (DOTS) in Nigeria. In-depth interviews and focus group discussion were used to study barriers to attendance at DOTS clinics for both prompt diagnosis and treatment of smear positive cases in Nigerian communities. A number of common and interrelated factors form barriers to use of DOTS clinics. These include perceived causes of the infection, for example witchcraft, that mitigate against an orthodox solution to TB and thereby affect perceived efficacy of DOTS. Another factor is perceived high cost in resource poor settings. Facility staff were noted to have demanded money from patients in spite of the fact that DOTS is advertised as free treatment. Furthermore, community members complain of the hostile attitude of health staff toward poor people as a barrier to community use of the facilities. It follows, therefore, that the attitude of health workers must be addressed if community members will use the DOTS clinics.

Pesticidas y salud en Huasahuasi, el Perú / Pesticides and health at Huasahuasi (Perú)

Informe de una investigación de inventario al uso de plaguicidas y a los efectos de salud en una población agraria en un pequeño andino. Contiene: 1.Sumario de literatura, antecedentes de aplicación de pesticidas. 2.Diseño metodológico de la investigación. 3.Descripción general de Huasahuasi. 4.La venta de pesticidas. 5.Fumigación y fumigadores. 6.Las familias. 7.Morbilidad por pesticidas. 8.Mortalidad por pesticidas. 9.Resumen de los resultados, conclusiones y recomendaciones; contiene además: cuadros y tres anexos