Predicting surgical intervention in patients presenting with carpal tunnel syndrome in primary care.

PURPOSE: Carpal tunnel syndrome (CTS) is a symptomatic compression neuropathy of the median nerve. This study investigated the value of candidate prognostic factors (PFs) in predicting carpal tunnel release surgery. PATIENTS AND METHODS: This is a retrospective cohort study set in the Clinical Practice Research Datalink. Patients ≥18 years presenting with an incident episode of CTS were identified between 1989 and 2013. Candidate PF's defined in coded electronic patient records were identified following literature review and consultation with clinicians. Time to first carpal tunnel release surgery was the primary end point. A manual backward stepwise selection procedure was used to obtain an optimal prediction model, which included all the significant PFs. RESULTS: In total, 91,412 patients were included in the cohort. The following PFs were included in an optimal model (C-statistic: 0.588 [95% CI 0.584-0.592]) for predicting surgical intervention: geographical region; deprivation status; age hazard ratio (HR 1.02 per year, 95% CI 1.01-1.02); obesity (HR 1.23, 95% CI 1.19-1.27); alcohol drinker (HR 1.05, 95% CI 1.00-1.10); smoker (HR 1.06, 95% 1.03-1.10); inflammatory condition (HR 1.13, 95% CI 0.98-1.29); neck condition (HR 1.13, 95% CI 1.03-1.23); and multisite pain (HR 1.10, 95% CI 1.05-1.15). Although not included in the multivariable model, pregnancy (if gender female) within 1 year of the index consultation, reduced the risk of surgery (HR 0.24, 95% CI 0.21-0.28). CONCLUSION: This study shows that patients who are older and who have comorbidities including other pain conditions are more likely to have surgery, whereas patients presenting with CTS during or within a year of pregnancy are less likely to have surgery. This information can help to inform clinicians and patients about the likely outcome of treatment and to be aware of which patients may be less responsive to primary care interventions.

Trends in the prevalence, incidence and surgical management of carpal tunnel syndrome between 1993 and 2013: an observational analysis of UK primary care records.

OBJECTIVES: To describe the prevalence, incidence and surgical management of carpal tunnel syndrome (CTS), between 1993 and 2013, as recorded in the Clinical Practice Research Datalink (CPRD). DESIGN: We completed a series of cross-sectional epidemiological analyses to observe trends over time. SETTING: Primary care data collected between 1993 and 2013, stored in the CPRD. POPULATION: Individuals aged ≥18 years were selected. Prevalent and incident episodes of CTS and episodes of surgical intervention were identified using a list of preidentified Read codes. ANALYSIS: We defined incident episodes as those with no preceding diagnostic code for CTS in the past 2 years of data. Episodes of surgery were expressed as a percentage of the prevalent population during the same calendar year. Joinpoint regression was used to determine significant changes in the underlying trend. RESULTS: The prevalence of CTS increased over the study period, with a particular incline between 2000 and 2004 (annual percentage change 7.81). The female-to-male prevalence ratio reduced over time from 2.74 in 1993 to 1.93 in 2013. The median age of females and males with CTS were noted to increase from 49 and 53 years, respectively in 1993 to 54 and 59 years, respectively in 2013. Incidence was also noted to increase over time. After an initial increase between 1993 and 2007, the percentage of prevalent patients with a coded surgical episode began to decrease after 2007 to 27.41% in 2013 (annual percentage change -1.7). CONCLUSION: This study has demonstrated that the prevalence and incidence of CTS increased over the study period between 1993 and 2013. Rates of surgery for CTS also increased over the study period; however after 2007, the per cent of patients receiving surgery showed a statistically significant decline back to the rate seen in 2004.

Clinical Course and Prognostic Factors in Conservatively Managed Carpal Tunnel Syndrome: A Systematic Review.

OBJECTIVE: To summarize the available evidence regarding the course of symptoms and prognostic factors in patients with diagnosed carpal tunnel syndrome (CTS) who are treated conservatively. DATA SOURCES: Computerized databases, reference checking, and experts in the field were used to identify studies for inclusion in the review. STUDY SELECTION: Multiple reviewers were used to identify studies which included adults (aged ≥18y) diagnosed with CTS in either a clinical setting or population setting. The study must have observed the course of CTS over at least a 6-week period in patients receiving no treatment or usual care that included conservative (nonsurgical) treatments. The design was of a longitudinal cohort study with either prospective or retrospective data collection. There were no language restrictions, and none of the research identified was only reported in abstract form. DATA EXTRACTION: Methodological bias was assessed using the Quality in Prognosis Studies tool. A high risk of bias (predominantly relating to study attrition, confounding, and/or statistical analysis and reporting) was judged to be present in 8 studies. Designs showed wide variability with respect to characteristics of the included population, definition of CTS, assessment of prognostic factors, types of interventions provided, and types of outcome measures applied. This prevented pooled estimates from being produced. DATA SYNTHESIS: A negative outcome at 3 years' follow-up of conservatively treated participants ranged from 23% to 89%. Four included studies observed the rate of surgical intervention after initial conservative management and found this to be 57% to 66%. Evidence regarding factors predicting the negative outcome of no treatment or conservative treatment was graded, taking into account the number of studies evaluating the factor, the methodological quality of these studies, and the consistency of the available evidence. There was 100% agreement in at least 3 cohorts with a medium or high risk of bias that symptom duration, a positive Phalen's test, and thenar wasting were associated with a negative outcome of conservative management; however, not all results were statistically significant, and hence the overall judgment remained inconclusive. CONCLUSIONS: Results of this review should be treated with caution because of the heterogeneity of studies and the risks of bias identified. However, the course of CTS appears variable, and poor prognosis may be predicted by a longer symptom duration, a positive Phalen's test, and thenar wasting.

The growth response of Escherichia coli to neurotransmitters and related catecholamine drugs requires a functional enterobactin biosynthesis and uptake system.

The neurotransmitter norepinephrine (NE) stimulates the growth of low inocula of Escherichia coli in a minimal medium (SAPI) supplemented with serum (SAPI+serum) and induces the production of an "autoinducer" (AI) which, in turn, promotes E. coli growth in the absence of NE. Given the importance of NE, epinephrine, and their corresponding adrenergic agonists and antagonists in clinical medicine, we sought to investigate the molecular basis for these observations. Using a variety of NE precursors, metabolites, and therapeutic agents, we demonstrated that their ability to stimulate E. coli growth in SAPI+serum is dependent on the presence of a catechol (1,2-dihydroxybenzene) moiety with maximal activity requiring a two-carbon substituent incorporating a terminal primary amine. Serum contains the iron-binding glycoprotein, transferrin, and when SAPI+serum was supplemented with sufficient Fe(3+) to saturate transferrin, growth inhibition was relieved. Other metal cations, including Mg(2+), Ca(2+), and Zn(2+), had no effect. These data suggested that the stimulation of E. coli growth by NE in SAPI+serum may involve the catecholate siderophore, enterobactin, a cyclic triester of 2,3-dihydroxybenzoylserine. Consistent with this hypothesis, E. coli strains with mutations in ferrienterobactin transport (fepA or tonB) or enterobactin biosynthesis (entA) did not respond to NE. Furthermore, NE induced expression of the ferrienterobactin receptor, FepA, during growth in SAPI+serum. The enterobactin degradation product, 2,3-dihydroxybenzoylserine (DBS) was as effective as NE in stimulating the growth of E. coli and mutations in fepA or tonB abolished the DBS-dependent growth stimulation. In contrast to NE, however, DBS stimulated the growth of the entA mutant. Moreover, after growth in an iron-limited M9 medium in the absence of NE, ethyl acetate extracts of the E. coli entA(+) parent but not of the entA mutant contained AI, i.e., stimulated the growth of E. coli in SAPI+serum. Taken together, these data show that when low numbers of E. coli are inoculated into SAPI+serum, NE, DBS, and related catecholamines induce the enterobactin iron uptake system. This, in turn, facilitates iron sequestration from transferrin and indicates that the AI present in NE-conditioned SAPI+serum medium is enterobactin and its DBS breakdown products.