Toronto Clinical Neuropathy Score is valid for a wide spectrum of polyneuropathies.

BACKGROUND AND PURPOSE: The Toronto Clinical Neuropathy Score (TCNS) is a valid and reliable scale for the diagnosis and staging of diabetic sensorimotor polyneuropathy. In this study, we aimed to explore the performance of the TCNS in non-diabetic polyneuropathies. METHODS: We performed a prospective study from November 2016 to May 2017 of patients with non-diabetic polyneuropathy. Patients had clinical, electrophysiological and functional assessments of their polyneuropathy, and the findings were correlated with the TCNS. RESULTS: The TCNS correlated with all clinical, electrophysiological and disability measures of polyneuropathy, mostly at a moderate level (e.g. r = -0.58 for sural nerve action potential amplitude). Higher TCNS severity grades were associated with worse polyneuropathy on all measures in the lower limbs, and with worse electrophysiological parameters and vibration perception thresholds in the upper limbs. The scale also showed excellent reliability and accuracy (kappa, 0.92-0.93 for inter- and intra-observer reliability; area under the receiver operating characteristics curve, 0.93). CONCLUSION: The TCNS is a valid and reliable scale for a wide spectrum of polyneuropathies, and might be useful in clinical practise and research for the diagnosis and staging of polyneuropathy.

Plasma uric acid effects on glomerular haemodynamic profile of patients with uncomplicated Type 1 diabetes mellitus.

AIMS: Increased plasma uric acid (PUA) levels are associated with impaired renal function in patients with Type 1 diabetes, but the mechanisms are not well understood. Our aim was to evaluate whether higher PUA levels are associated with increased afferent arteriolar resistance in patients with Type 1 diabetes vs. healthy controls, thereby influencing renal function. METHODS: PUA, GFR (inulin) and effective renal plasma flow (ERPF; para-aminohippurate) were measured in 70 otherwise healthy patients with Type 1 diabetes and 60 healthy controls. Gomez's equations were used to estimate afferent (RA ) and efferent (RE ) arteriolar resistances, glomerular hydrostatic pressure (PGLO ) and filtration pressure (ΔPF ). The relationships between PUA and glomerular haemodynamic parameters were evaluated by univariable linear regression correlation coefficients. RESULTS: In patients with Type 1 diabetes, higher PUA correlated with lower PGLO (P = 0.002) and ΔPF (P = 0.0007), with higher RA (P = 0.001), but not with RE (P = 0.55). These associations were accompanied by correlations between higher PUA with lower GFR (P = 0.0007), ERPF (P = 0.008), RBF (P = 0.047) and higher RVR (P = 0.021). There were no significant correlations between PUA and renal haemodynamic parameters in the healthy controls. CONCLUSIONS: The association between higher PUA with lower GFR and lower ERPF in patients with Type 1 diabetes is driven by alterations in the estimated RA . PUA-mediated RA may be caused by increased tone or thickening of the afferent renal arteriole, which might potentiate renal injury by causing ischaemia to the renal microcirculation.

Diabetes, trekking and high altitude: recognizing and preparing for the risks.

Although regular physical activity is encouraged for individuals with diabetes, exercise at high altitude increases risk for a number of potential complications. This review highlights our current understanding of the key physiological and clinical issues that accompany high-altitude travel and proposes basic clinical strategies to help overcome obstacles faced by trekkers with Type 1 or Type 2 diabetes. Although individuals with diabetes have adaptations to the hypoxia of high altitude (increased ventilation, heart rate, blood pressure and hormonal responses), elevated counter-regulatory hormones can impair glycaemic control, particularly if mountain sickness occurs. Moreover, high-altitude-induced anorexia and increased energy expenditure can predispose individuals to dysglycaemia unless careful adjustments in medication are performed. Frequent blood glucose monitoring is imperative, and results must be interpreted with caution because capillary blood glucose meter results may be less accurate at high elevations and low temperatures. It is also important to undergo pre-travel screening to rule out possible contraindications owing to chronic diabetes complications and make well-informed decisions about risks. Despite the risks, healthy, physically fit and well-prepared individuals with Type 1 or Type 2 diabetes who are capable of advanced self-management can be encouraged to participate in these activities and attain their summit goals. Moreover, trekking at high altitude can serve as an effective means to engage in physical activity and to increase confidence with fundamental diabetes self-management skills.

Variables associated with corneal confocal microscopy parameters in healthy volunteers: implications for diabetic neuropathy screening.

AIM: Corneal confocal microscopy is a promising screening method for diabetic neuropathy. Although much research in this field has been accomplished, we aimed to determine and confirm the known clinical and eyewear variables associated with the parameters of corneal confocal microscopy specifically in healthy volunteers, in particular associations with corneal nerve fibre length. METHODS: Clinical characteristics, electrophysiological examination and a general clinical eye history were collected from 64 healthy volunteers. Corneal confocal microscopy was performed to determine corneal nerve fibre length, corneal nerve branch density, corneal nerve fibre density and tortuosity coefficient. Univariate and multivariate linear regression analysis was used to determine clinical variables associated with corneal nerve fibre length parameters. RESULTS: We observed that corneal nerve fibre length has a broad distribution in healthy volunteers (18 ± 4 mm/mm(2), 95% confidence interval, 12.3-25.7 mm/mm(2)). Multivariate regression analysis demonstrated that HbA(1c) was the only independent clinical factor to account for variations in corneal nerve fibre length, independent of age and status of contact lens wear. CONCLUSIONS: This study does not provide convincing evidence that corneal nerve fibre length is independently associated with age or the wearing of contact lenses, and that these factors are therefore unlikely to hinder valid screening for polyneuropathies such as diabetic neuropathy. Furthermore, the strong inverse association of corneal nerve fibre length with glycaemic exposure may support the use of this parameter to detect subclinical pre-diabetic nerve injury.

Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management.

Painful diabetic peripheral neuropathy (DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been tested to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements, taking into consideration the co-morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include tricyclic anti-depressants, the selective serotonin and noradrenaline re-uptake inhibitors, anti-convulsants, opiates, membrane stabilizers, the anti-oxidant alpha-lipoic acid and topical agents including capsaicin. Current first-line therapies for painful DPN include tricyclic anti-depressants, the serotonin and noradrenaline re-uptake inhibitor duloxetine and the anti-convulsants pregabalin and gabapentin. When prescribing any of these agents, other co-morbidities and costs must be taken into account. Second-line approaches include the use of opiates such as synthetic opioid tramadol, morphine and oxycodone-controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated. There are a number of unmet needs in the therapeutic management of painful DPN. These include the need for randomized controlled trials with active comparators and data on the long-term efficacy of agents used, as most trials have lasted for less than 6 months. Finally, there is a need for appropriately designed studies to investigate non-pharmacological approaches.

Reproducibility of in vivo corneal confocal microscopy as a novel screening test for early diabetic sensorimotor polyneuropathy.

AIM: With the goal of identifying a valid biomarker of early diabetic sensorimotor polyneuropathy, we aimed to identify the most reliable in vivo corneal confocal microscopy (CCM) parameter for detection of abnormality of small nerve fibre morphology. METHODS: Cross-sectional examination of 46 subjects (26 with Type 1 diabetes and 20 healthy volunteers) examined by corneal confocal microscopy for intra- and interobserver reproducibility by the intraclass correlation coefficient method. Corneal nerve fibre density, nerve branch density, nerve fibre length and tortuosity were measured on the same day that subjects underwent clinical and electrophysiological examination. RESULTS: The 26 subjects with Type 1 diabetes had mean age and diabetes duration 42.8 ± 16.9 and 22.7 ± 16.4 years, respectively. Twelve of those subjects (46%) did not meet criteria for diabetic sensorimotor polyneuropathy, while five (19%) had mild, three (12%) had moderate and six (23%) had severe diabetic sensorimotor polyneuropathy. None of the healthy volunteers (mean age 41.4 ± 17.3 years) had polyneuropathy. Re-examination of selected corneal confocal microscopy images or sets of 40 images yielded very good to excellent intraclass correlation coefficients for all parameters. However, only one parameter (corneal nerve fibre length) emerged with consistently very good reproducibility using a clinically relevant 'study-level' protocol of subject re-examination (intra-observer intraclass correlation coefficient 0.72; interobserver intraclass correlation coefficient 0.73). Despite no differences in intraclass correlation coefficient between subgroups, corneal nerve fibre length was significantly lower (14.76 vs. 16.15 mm/mm(2), P = 0.04) in those with diabetes. CONCLUSIONS: Development of corneal confocal microscopy may need to focus on the measurement of corneal nerve fibre length, as it appears to have superior reliability in comparison with other parameters, and as evidence exists for its potential as a clinical biomarker of early diabetic sensorimotor polyneuropathy.

Short-term metabolic change is associated with improvement in measures of diabetic neuropathy: a 1-year placebo cohort analysis.

AIMS: Randomized clinical trials have frequently shown improvement in diabetic sensorimotor polyneuropathy in placebo-treated participants, counter to the prevailing concept that it deteriorates with time. We aimed to determine the variables associated with this paradoxical nerve function improvement. METHODS: Participants with diabetic sensorimotor polyneuropathy randomized to placebo in a multi-centre, double-blind study were evaluated for the primary outcome of 1-year change in the summed sensory nerve conduction velocity of the bilateral sural and non-dominant median nerves. Association with clinical and biochemical variables measured at 13 time points were examined. RESULTS: The 134 participants had mild to moderate diabetic sensorimotor polyneuropathy of 4.6 years' duration and mean 1-year improvement of 2.0 ± 8.0 m/s. Primary outcome measures were available for 122 participants (91%). In multivariate analyses, the change in HbA(1c) and serum triglycerides from baseline to 2 months demonstrated the strongest association, even independent of baseline and end-of-study levels. According to quintiles of change, we determined thresholds: participants with salutary improvement in HbA(1c) (exceeding a drop of -0.8%) or whose triglycerides did not increase (by 0.32 mmol/l or more) experienced significant improvement (2.9 m/s), while those with salutary levels of both these variables had an exaggerated improvement (5.1 m/s). In comparison, those with non-salutary changes in both variables experienced a loss of -4.9 m/s (ANOVA P=0.0014). CONCLUSIONS: In mild to moderate diabetic sensorimotor polyneuropathy, short-term improvements in glycaemic control and serum triglyceride levels have an independent, additive and durable effect on restoration of nerve function.

Ability of cystatin C to detect acute changes in glomerular filtration rate provoked by hyperglycaemia in uncomplicated Type 1 diabetes.

AIMS: Systematic study of hyperfiltration in diabetic nephropathy has been hindered by the lack of a simple glomerular filtration rate (GFR) measure that is accurate in this range of renal function. Serum cystatin C (GFR(CYSTATIN C) ) reflects long-term trends in GFR in normal or elevated ranges. To test whether it can reflect acute changes, we examined the impact of clamped hyperglycaemia on GFR(CYSTATIN C) and GFR(INULIN) in subjects with Type 1 diabetes. METHODS: GFR(INULIN) and GFR(CYSTATIN C) were measured in 32 normotensive, normoalbuminuric subjects during clamped euglycaemia and hyperglycaemia. For comparison, GFR(MDRD) was estimated according to the four-variable equation. RESULTS: During clamped euglycaemia, agreement between GFR(CYSTATIN C) and GFR(INULIN) was excellent, with mean bias +1.9 (90% distribution -29 to +31) ml min(-1) 1.73 m(-2), while GFR(MDRD) had mean bias +11.4 (-45 to +51) ml min(-1) 1.73 m(-2). With exposure to clamped hyperglycaemia, the mean increase in GFR(CYSTATIN C) (+17.5 ± 13.5 ml min(-1) 1.73 m(-2) ) reflected that observed with GFR(INULIN) (+15.3 ± 28.1 ml min(-1) 1.73 m(-2), P = 0.74), while GFR(MDRD) demonstrated a mean decline of -4.4 ± 33.6 ml min(-1) 1.73 m(-2) (P = 0.01). In all 24 subjects in whom GFR(INULIN) increased in response to hyperglycaemia, GFR(CYSTATIN C) reflected a concordant change (sensitivity, 100%) while GFR(MDRD) increased in 10/24 (sensitivity, 42%). In the eight remaining subjects, specificity was 25 and 75% for GFR(CYSTATIN C) and GFR(MDRD), respectively. CONCLUSION: GFR(CYSTATIN C) reflects normal and elevated renal function better than GFR(MDRD) even under the acute influences of hyperglycaemia, suggesting a role for cystatin C in clinical practice and research for the study of early renal function changes in Type 1 diabetes.

SGLT2 inhibition increases serum copeptin in young adults with type 1 diabetes.

AIMS: Copeptin, a surrogate of vasopressin, is elevated in type 1 diabetes (T1D) and predicts kidney disease and cardiovascular mortality. Given the cardiorenal protective effects of SGLT2 inhibition (SGLT2i), our aim was to examine: 1) the relationship between serum copeptin, metabolic, renal and systemic hemodynamic parameters in adults with T1D; and 2) serum copeptin after SGLT2i with empagliflozin. MATERIALS AND METHODS: In this post-hoc, exploratory analysis, serum copeptin, glomerular filtration rate (GFRInulin), effective renal plasma flow (ERPFPAH), plasma renin angiotensin aldosterone system markers, HbA1c, 24-hour urine volume and sodium excretion were measured in 40 participants with T1D (24.3±5.1 years) during eu- and hyperglycaemia before and after 8 weeks of 25mg of daily empagliflozin. RESULTS: Higher baseline copeptin correlated with higher HbA1c, lower 24-hour urine volume and sodium excretion, after correcting for age, sex, systolic blood pressure, and HbA1c. Copeptin concentrations increased in response to empagliflozin under euglycaemia (4.1±2.1 to 5.1±2.8pmol/L, P=0.0053) and hyperglycaemia (3.3±1.4 to 5.6±2.8pmol/L, P<0.0001). The rise in copeptin in response to empagliflozin correlated with change in 24-hour urine volume, but was independent of changes in fractional excretion of sodium and haematocrit. CONCLUSIONS: Elevated serum copeptin was associated with worse glycaemic control and lower diuresis and natriuresis. SGLT2i increased serum copeptin in adults with T1D, and the rise correlated with change in diuresis, but not natriuresis and hemo-concentration. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i, including whether it is simply a marker of diuresis or may contribute to cardiorenal disease long-term.

Reliability and validity of the modified Toronto Clinical Neuropathy Score in diabetic sensorimotor polyneuropathy.

INTRODUCTION: A reliable and valid clinical tool to capture symptoms and signs of diabetic sensorimotor polyneuropathy (DSP) for use in clinical research trials is urgently needed. The validated Toronto Clinical Neuropathy Score (TCNS) was modified to improve sensitivity to early DSP changes. We aimed to assess the reproducibility of this modified tool, the mTCNS and to determine its validity relative to the precursor TCNS. METHODS: Sixty-five patients (six Type 1, 59 Type 2 diabetes) with diabetes duration 13 +/- 8 years were accrued from four study sites and examined on 2 days for internal consistency and inter- and intra-rater reliability of the mTCNS. In the absence of a single quantitative gold-standard measure for DSP, results of the mTCNS were compared with the precursor TCNS for the purpose of estimating validity. RESULTS: Internal consistency of the two domains within the mTCNS was good (Cronbach's alpha 0.78). Very good inter-rater reliability for the mTCNS was demonstrated by an intra-class correlation coefficient for the mTCNS of 0.87 (95% confidence interval, 0.79-0.91), which was similar in magnitude to that of the TCNS (0.83; 95% confidence interval, 0.75-0.89). Intra-rater reliability testing of the mTCNS showed moderate to good correlation for individual symptoms and sensory tests (Cohen's kappa values of 0.54-0.73). The mTCNS shared moderate correlation with the precursor TCNS (Pearson correlation coefficient, 0.58). DISCUSSION: The mTCNS, a clinical score with higher face validity for tracking mild to moderate DSP, has sufficient reliability and validity relative to its precursor TCNS for use in clinical research.

Leptospirosis among patients presenting with dengue-like illness in Puerto Rico.

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.

Glycemic control is related to the morphological severity of diabetic sensorimotor polyneuropathy.

OBJECTIVE: The aim of the current study was to determine the independent clinical risk factors for predicting morphological severity of distal diabetic sensorimotor polynecuropathy (DSP) as determined by fiber density (FD) on sural nerve biopsy. RESEARCH DESIGN AND METHODS: A total of 89 patients with both type 1 and type 2 diabetes, ascertained from a large therapeutic randomized clinical trial, were included in this observational cohort study. Morphological severity of DSP was expressed as the myelinated FD in the sural nerve biopsy General linear models were used to assess the relationship between the morphological severity of DSP and various clinical risk factors. RESULTS: Glycated hemoglobin (GHb) was significantly related to FD in univariate and multivariate regression analyses. This relationship was present in models in which GHb was handled either as a continuous variable or as a categorical variable with the highest significance level, with a GHb cutoff level of 9%. After dividing patients into groups with optimal to moderate GHb < or = 9%) and suboptimal (GHb >9%) glycemic control, the difference in FD between the two groups ranged between 3,461 and 2,334 per mm2. FD was also significantly related to duration of diabetes and age of the patient. CONCLUSIONS: The severity of peripheral DSP expressed by morphological criteria was significantly related to glycemic control in type 1 and type 2 diabetic patients. Inconsistent with previously published electrophysiological data demonstrating a correlation between height and conduction velocity, increasing height is not associated with morphological severity. Based on the results of the present study, it might be hypothesized that improving glycemic control will lessen severity of DSP in terms of FD loss in subjects with diabetes.

Simple screening tests for peripheral neuropathy in the diabetes clinic.

OBJECTIVE: The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy. RESEARCH DESIGN AND METHODS: We assessed four simple tests (the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test. RESULTS: The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34, and 0.50, respectively The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring approximately 60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test. CONCLUSIONS: Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy.

Serologic responses to Bartonella and Afipia antigens in patients with cat scratch disease.

OBJECTIVE: To assess the serologic response to Afipia and Bartonella, previously named Rochalimaea, in patients with cat scratch disease (CSD) and a healthy control group. DESIGN: Prospective, controlled trial. SETTING: Referral clinic and hospitalized patients in a university medical center. PARTICIPANTS: Eighty patients with CSD and 57 healthy control subjects of similar age. MAIN OUTCOME MEASURES: The immune responses to Afipia felis and Bartonella henselae were evaluated by a newly developed enzyme-linked immunosorbent assay (ELISA) in patients with CSD and healthy control subjects. Responses to B henselae were also measured by indirect fluorescent antibody (IFA) tests. Antibody levels to Bartonella quintana were measured by ELISA and IFA in a limited number of patients and control subjects. RESULTS: Of the 80 patients with clinical CSD, 56 had positive results of CSD skin tests. ELISA antibody levels to A felis did not differ between patients and control subjects, but immunoglobulin M (IgM) and IgG ELISA antibodies to B henselae and B quintana were significantly higher in patients than in control subjects. IFA responses to B henselae and B quintana were also significantly higher in patients than in control subjects. CONCLUSION: Patients with CSD had significant serologic responses to B henselae and B quintana but not to A felis, suggesting that the causative agent of CSD is antigenically related to the Bartonella genus and not to Afipia. The Bartonella IgM ELISA and IFA assay were both sensitive and specific and may be used to establish the diagnosis of CSD.

Comparative efficacy of oral rifampin and topical chloramphenicol in eradicating conjunctival carriage of Haemophilus influenzae biogroup aegyptius. Brazilian Purpuric Fever Study Group.

Persistent conjunctival carriage of the Haemophilus influenzae biogroup aegyptius (Hae) strain (BPF clone) responsible for Brazilian purpuric fever (BPF) has been documented. Topical chloramphenicol is routinely used to treat conjunctivitis in areas affected by BPF in Brazil. Although the BPF clone is susceptible to chloramphenicol, we observed a number of children treated with topical chloramphenicol for conjunctivitis who still developed BPF. During an investigation of an outbreak of BPF in Mato Grosso State, Brazil, we compared oral rifampin (20 mg/kg/day for 4 days) with topical chloramphenicol for eradication of conjunctival carriage of H. influenzae biogroup aegyptius among children with presumed BPF clone conjunctivitis. Conjunctival samples were taken for culture on the day treatment was initiated and a mean of 8 and 21 days later. At 8 days the eradication rates for oral rifampin and topical chloramphenicol were 100 and 44%, respectively (P = 0.003); at 21 days they were 100 and 50% (P = 0.01). Oral rifampin was more effective than topical chloramphenicol for eradication of the BPF clone and may be useful in prevention of BPF.

Tobacco smoke as a risk factor for meningococcal disease.

BACKGROUND: Since 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease. The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N. meningitidis serogroup B. Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance. METHODS: We performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls. We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures. RESULTS: After adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children < 18 years of age [odds ratio (OR), 3.8; 95% confidence interval (CI) 1.6 to 8.9)], with 37% (CI 15 to 65) of all cases in this age group potentially attributable to maternal smoking. Adult patients were more likely than controls to have a chronic underlying illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco (OR 2.4, CI 0.9 to 6.6). Dose-response effects were seen for passive smoke exposure and risk of disease in all age groups. CONCLUSION: Tobacco smoke exposure independently increases the risk of developing meningococcal disease.

Asymptomatic infection and risk factors for leptospirosis in Nicaragua.

As part of an investigation of a 1995 outbreak of leptospirosis in Nicaragua, a cross-sectional serologic survey was conducted in the town of El Sauce. Of 566 persons, 85 (15%) were positive for IgM anti-Leptospira antibodies, indicating recent leptospirosis infection. Asymptomatic leptospirosis infection was common, with only 25 (29.4%) of the 85 seropositive inhabitants reporting a febrile illness in the 2 months before the survey. Multivariable analysis revealed that having an indoor water source remained independently protective against leptospirosis. Gathering wood was independently associated with infection. These findings suggest that asymptomatic infection with Leptospira is common in endemic areas of Leptospira transmission. Improvement in water sanitation and behavioral modifications to reduce environmental exposure may reduce the risk of leptospirosis in endemic regions.

Evaluation of three screening tests and a risk assessment model for diagnosing peripheral neuropathy in the diabetes clinic.

OBJECTIVE: with the aim of evaluating predictive power, three simple screening tests as alternates to nerve conduction tests for diagnosing diabetic peripheral neuropathy (DPN) were investigated. Results of the screening tests, along with the subjects' demographic and clinical characteristics, were planned as the variables for the development of a risk assessment tool for predicting DPN. DESIGN: this is a cross-sectional multi-group comparison study. The study utilized a predictive model derived from one subset of the study population, and prospectively tested in the other subset to predict the presence of neuropathy. SETTING: Diabetic Neuropathy Research Clinic of the Toronto General Hospital and University Health Network in Toronto, Ontario, Canada from June 1998 to August 1999. SAMPLE POPULATION: data come from 478 subjects consisting of non-diabetic reference subjects, and patients with type 1 and type 2 diabetes mellitus. OUTCOMES MEASURES: nerve conduction studies (NCS) comprised the primary defined outcome. The three screening sensory tests examined in the study were the Semmes-Weinstein 10 g monofilament examination (SWME), superficial pain sensation, and vibration by the on-off method. RESULTS: the three screening tests are significantly and positively correlated with NCS. An increase in the number of insensate responses in the screening test is associated with an increase in the abnormal NCS score. The strength of the association between NCS and each sensory test was greater when the neuropathy severity stage of the subject was added to the model. Both the SWME and vibration by the on-off method tests demonstrated sufficient statistical power to differentiate non-diabetic control subjects from subjects with diabetes, as well as to differentiate subjects with diabetes with and without neuropathy. These two tests, when compared with NCS, also demonstrated acceptable diagnostic performance characteristics in terms of high sensitivity and specificity, total number of correctly predicted cases, and receiver-operating characteristic curves. CONCLUSION: this data, through the development of a model involving training and validation sets, demonstrates that the knowledge of clinical risk factors alters the interpretation of sensory tests for DPN. This finding lends further support to the validity of simple sensory testing maneuvers in the conditional diagnosis of DPN. We recommend annual screening with either the SWME or vibration by the on-off method in the primary care and diabetes clinics.

Update on Haemophilus influenzae serotype b and meningococcal vaccines.

Use of conjugate Haemophilus influenzae type b (Hib) vaccines has resulted in the near elimination of Hib invasive disease among infants in the United States in only 10 years, which places this intervention among the most notable public health achievements of the past decade. This has radically altered our perception of the major causes of bacterial meningitis and invasive bacterial disease among children, increasing the prominence of meningococcal disease as an important cause of childhood and adult meningitis and leading researchers to apply the same conjugate technology to the development of improved vaccines for Neisseria meningitidis. Use of conjugated meningococcal vaccines against serogroups A, C, Y, and W-135 are expected to offer the possibility of better control of sporadic disease and outbreaks throughout developed and developing countries within the next 5 years.

[Isolation of Haemophilus aegyptius associated with Brazilian purpuric fever, of Chloropidae (Diptera) of the genera Hippelates and Liohippelates]. / Isolamento de Haemophilus aegyptius associado à febre purpúrica brasileira, de cloropídeos (Diptera) dos gêneros Hippelates e Liohippelates.

The recognition of the Brazilian purpuric fever (BPF) in 1984 led to a number of studies which showed a relation between this disease and conjunctivitis caused by Haemophilus aegyptius. The increase in cases of conjunctivitis in children associated with higher population density of eye gnats (Chloropidae: Hippelates) has been reported since last century. This phenomenon is related to the attraction that those flies show for the eyes, secretions and wounds, from where they feed on. Although there are evidences on the role of these flies in the mechanical transmission of seasonal bacterial conjunctivitis, the isolation of Haemophilus aegyptius from them in their natural habitat had not been demonstrated yet. In this study Haemophilus aegyptius associated to BPF was isolated from two pools of chloropids collected around the eyes of children with conjunctivitis which were identified as Liohippelates peruanus (Becker) and a new species Hippelates neoproboscideus.