Robin M. T. Cooke

Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types.

Background— Most studies of amyloidotic cardiomyopathy consider as a single entity the 3 main systemic cardiac amyloidoses: acquired monoclonal immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared the diagnostic/clinical profiles of these 3 types of systemic cardiac amyloidosis. Methods and Results— We conducted a longitudinal study of 233 patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157; ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were elderly men. At diagnosis, mean left ventricular wall thickness was higher in ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed low QRS voltage (25% versus 60% in AL; P<0.0001) or low voltage-to-mass ratio (1.1±0.5 versus 0.9±0.5; P<0.0001). AL patients appeared to have greater hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable predictor of survival, and ATTRwt predicted freedom from major cardiac events. Conclusions— AL, ATTRm, and ATTRwt should be considered 3 different cardiac diseases, probably characterized by different pathophysiological substrates and courses. Awareness of the diversity underlying the cardiac amyloidosis label is important on several levels, ranging from disease classification to diagnosis and clinical management.

Carpal tunnel syndrome and manual work: a longitudinal study.

Objective: To assess risks associated with work-related biomechanical overloads in onset/course of carpal tunnel syndrome. Methods: Workgroups with job tasks spanning different biomechanical exposures were evaluated at baseline in terms of American Conference of Governmental Industrial Hygienists hand-activity/peak force action limit and threshold limit values (TLV). Exposures of interest were “unacceptable” (hand-activity above TLV) and “borderline” (between action limit and TLV) overloads. Clinical/individual data were collected at baseline and 12 months. Results: One-year incidence of “classic/possible” carpal tunnel syndrome symptoms as defined by consensus criteria was 7.3% (153 of 2092). “Unacceptable” overload was associated with a 3-fold increased risk of onset with respect to “acceptable” load. At ordered logistic regression analysis of symptom-status variations, increased risks were recorded for “unacceptable” and “borderline” overloads. Conclusions: Effectiveness of encouraging workplace adherence to the American Conference of Governmental Industrial Hygienists recommendations deserves investigation as a possible key to wide-scale prevention.

Available instruments for measurement of psychosocial factors in the work environment

ObjectiveTo provide an overview of the spectrum of available for measurement and evaluation of work-related psychosocial factors.MethodsWe systematically searched the literature/internet to identify and describe the main available questionnaires and observational instruments for assessment of work-related psychosocial factors (with/without other job stressors).ResultsA total of 33 instruments were identified (26 questionnaires, 7 observational), many (11 questionnaires, 5 observational) linked to national institutions/intiatives. Accessibility of relevant information (on the internet or elsewhere) regarding the instruments varied widely.ConclusionsThis summary of the range of instruments currently available for evaluation of multiple work stressors at individual, group and/or organizational levels may provide a useful tool for operators and researchers.

Gender-related risk of myocardial involvement in systemic amyloidosis

To investigate associations between gender and myocardial involvement in systemic amyloidosis, we reviewed all patients presenting between 1994 and September 2006 in our institutional network (100 AL and 98 familial transthyretin-related amyloidosis (ATTR) patients, plus 12 elderly men with senile systemic amyloidosis). We focused on echocardiographic descriptors of myocardial involvement (height-indexed mean left ventricular (LV) wall thickness, LV mass index), and baseline LV function. Among familial ATTR patients, female prevalence was lower within the highest tertile of either echocardiographic indicator of myocardial involvement. Gender was independently associated with height-indexed mean LV wall thickness (as were gene mutations). Female prevalence appeared rather similar across the different neurological stages. Within the subgroup of familial ATTR patients with amyloidotic cardiomyopathy, women tended to display a considerably less severe morphological and functional echocardiographic profile. We explored the possible role of female sex hormones by considering menopausal status: women in the highest tertile of mean LV wall thickness index were more often postmenopausal than those in the other two tertiles and had a much higher (∼15 years) mean age; analogous age-related associations were not observable for men. In conclusion, these findings raise the hypothesis that some biological characteristic associated with female gender protects against myocardial involvement in familial ATTR.

Phenotypic and genotypic heterogeneity in transthyretin-related cardiac amyloidosis: Towards tailoring of therapeutic strategies?

Transthyretin-related hereditary amyloidosis (ATTR) is genotypically/phenotypically heterogeneous. We investigated myocardial involvement in ATTR in a cohort of patients with a wide range of mutations. Clinical/echocardiographic follow-up of 41 consecutive symptomatic ATTR patients from a single referral center was analyzed according to TTR mutation. Diagnosis was based on histology, immunohistochemistry and genotyping. Median follow up was 40 months (range 8–120). Among the 12 different mutations identified, Val30Met was found in 10 patients and Glu89Gln in seven. Compared with Val30Met, Glu89Gln was associated with higher LV mass index, lower left ventricular ejection fraction and shorter E-wave deceleration time. All Glu89Gln carriers had cardiomyopathy, which was more severe (for left ventricular thickness, left ventricular mass and restrictive pathophysiology) than in the six affected Val30Met patients. Glu89Gln was independently associated with higher risk of major cardiovascular events among cardiomyopathy patients. This follow-up study of ATTR patients carrying a wide range of mutations indicates that (1) cardiac involvement is a very important component of phenotypic expression; and (2) genotype is an important source of heterogeneity in myocardial involvement, with Glu89Gln being associated with a severe, heart-driven prognosis. We think that combined heart–liver transplantation could be considered for Glu89Gln carriers with established, morphologically severe cardiomyopathy.

Search strings for the study of putative occupational determinants of disease.

Objective To identify efficient PubMed search strategies to retrieve articles regarding putative occupational determinants of conditions not generally considered to be work related. Methods Based on MeSH definitions and expert knowledge, we selected as candidate search terms the four MeSH terms describing ‘occupational disease’, ‘occupational exposure’, ‘occupational health’ and ‘occupational medicine’ (DEHM) alongside 22 other promising terms. We first explored overlaps between the candidate terms in PubMed. Using random samples of abstracts retrieved by each term, we estimated the proportions of articles containing potentially pertinent information regarding occupational aetiology in order to formulate two search strategies (one more ‘specific’, one more ‘sensitive’). We applied these strategies to retrieve information on the possible occupational aetiology of meningioma, pancreatitis and atrial fibrillation. Results Only 20.3% of abstracts were retrieved by more than one DEHM term. The more ‘specific’ search string was based on the combination of terms that yielded the highest proportion (40%) of potentially pertinent abstracts. The more ‘sensitive’ string was based on the use of broader search fields and additional coverage provided by other search terms under study. Using the specific string, the numbers of abstracts needed to read to find one potentially pertinent article were 1.2 for meningioma, 1.9 for pancreatitis and 1.8 for atrial fibrillation. Using the sensitive strategy, the numbers needed to read were 4.4 for meningioma, 8.9 for pancreatitis and 10.5 for atrial fibrillation. Conclusions The proposed strings could help health care professionals explore putative occupational aetiology for diseases that are not generally thought to be work related.

Risk factors for operated carpal tunnel syndrome: a multicenter population-based case-control study.

BackgroundCarpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS.MethodsCases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates.ResultsAt multivariate analysis, risk factors were blue-collar/housewife status, BMI ≥ 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women ≥165 cm; men ≥175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force.ConclusionThis study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS.

Randomized comparative trial of a thin‐strut bare metal cobalt‐chromium stent versus a sirolimus‐eluting stent for coronary revascularization

OBJECTIVES: To see whether use of a sirolimus‐eluting stent (SES) is superior to a third‐generation thin‐strut, cobalt‐chromium stent (CCS) in terms of in‐segment late loss at 9 months in patients with symptomatic coronary artery disease. BACKGROUND: Stent‐strut thickness has been shown to be strictly related with risk of in‐stent restenosis, but available demonstrations of the angiographic efficacy of SES have been based on comparisons with thick‐strut bare metal control stents. METHODS: The primary outcome measure of this single‐center, single‐blind randomized comparative trial was 9‐month in‐segment late loss. Eligibility criteria were symptomatic coronary artery disease and target vessel diameter appropriate for implantation a 3‐mm stent. Based on a power calculation, 104 patients were randomly assigned to receive a SES (Cypher™) or a CCS (Vision™). RESULTS: In‐segment late loss was significantly lower in the SES group (0.18 ± 0.40 mm vs 0.58 ± 0.51 mm, P < 0.001). Regarding subsidiary outcome measures, in‐segment restenosis (at 9 months) was recorded in 10% (5/50) patients treated with SES and 23% (11/48) receiving CCS (P = 0.14). No clinical difference between the two groups was apparent at 12 months. Freedom from target vessel failure at 12 months was 72% for SES patients and 68% for CCS patients (P = 0.65). CONCLUSIONS: In patients with de‐novo coronary lesions at medium risk of restenosis the anti‐proliferative effect of SES is greater than that of a thin‐strut CCS. Nevertheless, the angiographic results of the CCS were rather good. It remains to be seen whether the angiographic superiority of SES can translate into clinical superiority.

Incidence rates of surgically treated idiopathic carpal tunnel syndrome in blue- and white-collar workers and housewives in Tuscany, Italy

Objectives: Rates of surgically treated carpal tunnel syndrome (CTS) among blue- and white-collar workers and housewives in the general population were compared. Methods: Surgically treated cases of idiopathic CTS were investigated among 25–59-year-old residents of Tuscany, Italy, during 1997–2000, based on obligatory discharge records from all Italian public/private hospitals, archived according to residence on Tuscany’s regional database. Population data were extracted from the 2001 census. Results: After excluding repeat admissions, 8801 eligible cases were identified. Age-standardised rates (per 100 000 person-years) of surgical CTS were: “blue-collar women”, 367.8; “white-collar women”, 88.1; “housewives”, 334.5; “blue-collar men”, 73.5; and “white-collar men”, 15.3. Compared with reference categories (same-sex white-collar workers): female blue-collar workers experienced a 4.2-fold higher standardised rate; housewives, a 3.8-fold excess; and male blue-collar workers, a 4.8-fold excess (all p<0.001). Male and female blue-collar workers showed approximately three to sevenfold higher age-specific rates compared to their white-collar counterparts (all p<0.001). Housewives’ rates were similar to those of blue-collar female workers up to 40–44 years of age, after which they were significantly lower (p<0.002). At all ages, housewives’ rates were much higher (p<0.001) than those of white-collar women. Conclusions: Surgically treated CTS was three to seven times more common (depending on age/gender) in blue-collar than in white-collar workers, which is difficult to explain by differences in body weight or other individual factors. Thus, occupational risk factors seem relevant throughout working life. The high rates for full-time housewives suggest that domestic chores should be investigated as a possible risk factor for CTS.

Incidence rates of in-hospital carpal tunnel syndrome in the general population and possible associations with marital status

BackgroundCarpal tunnel syndrome (CTS) is a socially relevant condition associated with biomechanical risk factors. We evaluated age-sex-specific incidence rates of in-hospital cases of CTS in central/northern Italy and explored relations with marital status.MethodsSeven regions were considered (overall population, 14.9 million) over 3–6-year periods between 1997 and 2002 (when out-of-hospital CTS surgery was extremely rare). Incidence rates of in-hospital cases of CTS were estimated based on 1) codified demographic, diagnostic and intervention data in obligatory discharge records from all Italian public/private hospitals, archived (according to residence) on regional databases; 2) demographic general population data for each region. We compared (using the χscore test) age-sex-specific rates between married, unmarried, divorced and widowed subsets of the general population. We calculated standardized incidence ratios (SIRs) for married/unmarried men and women.ResultsAge-standardized incidence rates (per 100,000 person-years) of in-hospital cases of CTS were 166 in women and 44 in men (106 overall). Married subjects of both sexes showed higher age-specific rates with respect to unmarried men/women. SIRs were calculated comparing married vs unmarried rates of both sexes: 1.59 (95% confidence interval [95% CI], 1.57–1.60) in women, and 1.42 (95% CI, 1.40–1.45) in men. As compared with married women/men, widows/widowers both showed 2–3-fold higher incidence peaks during the fourth decade of life (beyond 50 years of age, widowed subjects showed similar trends to unmarried counterparts).ConclusionThis large population-based study illustrates distinct age-related trends in men and women, and also raises the question whether marital status could be associated with CTS in the general population.