Validation of self-reported help-seeking, and measurement of the patient interval, for cancer symptoms: an observational study to inform methodological challenges in symptomatic presentation research.

BACKGROUND: To improve earlier presentation with potential symptoms of cancer, accurate data are needed on how people respond to these symptoms. It is currently unclear how self-reported medical help-seeking for symptoms associated with cancer by people from the community correspond to what is recorded in their general practice records, or how well the patient interval (time from symptom onset to first presentation to a health-professional) can be estimated from patient records. METHOD: Data from two studies that reviewed general practice electronic records of residents in Scotland, (i) the 'Useful Study': respondents to a general population survey who reported experiencing symptoms potentially associated with one of four common cancers (breast, colorectal, lung and upper gastro-intestinal) and (ii) the 'Detect Cancer Early' programme: cancer patients with one of the same four cancers. Survey respondents' self-reported help-seeking (yes/no) was corroborated; Cohen's Kappa assessed level of agreement. Combined data on the patient interval were evaluated using descriptive analysis. RESULTS: 'Useful Study' respondents' self-report of help-seeking showed exact correspondence with general practice electronic records in 72% of cases (n = 136, kappa 0.453, moderate agreement). Between both studies, 1269 patient records from 35 general practices were reviewed. The patient interval could not be determined in 44% (n = 809) of symptoms presented by these individuals. CONCLUSIONS: Patient self-report of help-seeking for symptoms potentially associated with cancer offer a reasonably accurate method to research responses to these symptoms. Incomplete patient interval data suggest routine general practice records are unreliable for measuring this important part of the patient's symptom journey.

Why do patients discontinue antidepressant therapy early? A qualitative study.

BACKGROUND: Current guidelines for antidepressant prescribing are that treatment should be continued following the resolution of symptoms: six months after a first episode and for at least two years for those with previous episodes. Despite this, sub-optimal treatment duration still predominates. Patients have negative and positive views on antidepressants, which change throughout their treatment journey. OBJECTIVES: To explore views and experiences of patients recently initiated on antidepressants (within six months), and to consider the influences on early discontinuation. METHODS: A qualitative interview study was used in four general practices in the North East of Scotland. A purposive sample of primary care patients, newly initiated on antidepressants, was interviewed to explore views and experiences with antidepressant therapy. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted using a consensus coding frame developed by two researchers. RESULTS: Twenty-nine patients participated. Three main factors influencing discontinuation were identified: ownership, knowledge and support. The treatment journey was characterized by four important time points where health care intervention may be helpful. CONCLUSION: Health care professionals would benefit from exploring patient knowledge and views on depression and antidepressants at an early stage in treatment. Patients would welcome active involvement in treatment decision making, the provision of information and ongoing support.

Psychometric properties of the Quick Inventory of Depressive Symptomatology (QIDS-SR) in UK primary care.

It is widely believed that severity of depressive disorder should guide treatment selection and many guidelines emphasise this factor. The Quick Inventory of Depressive Symptomatology (QID-SR16) is a self-complete measure of depression severity which includes all DSM-IV criterion symptoms for major depressive disorder. The object of this study was to assess the psychometric properties of the QIDS-SR16 in a primary care sample. Adult primary care patients completed the QIDS-SR16 and were assessed by a psychiatrist (blind to QIDS-SR16) with the 17-item Hamilton Rating Scale for Depression (GRID-HAMD). Internal consistency, homogeneity and convergent and discriminant validity of the QIDS-SR16 were assessed. Severity cut-off scores for QIDS-SR16 were assessed for convergence with HRSD-17 cut-offs. Published methods for converting scores to HRSD-17 were also assessed. Two hundred and eighty-six patients participated: mean age = 49.5 (s.d. = 13.8), 68% female, mean HRSD-17 = 12.6 (s.d. = 7.6). The QIDS-SR16 exhibited acceptable internal consistency (Cronbach's alpha = 0.86), a robust factor structure indicating one underlying dimension and correlated highly with the HRSD-17 (r = 0.79) but differed significantly in how it categorised the severity of depression relative to the HRSD-17 (Wilcoxon Signed Rank Test p < 0.001). Using published methods to convert QIDS-SR16 scores to HRSD-17 scores did not result in alignment of severity categorisation. In conclusion, psychometric properties of the QIDS-SR16 were found to be strong in terms of internal consistency, factor structure and convergent and discriminant validity. Using conventional scoring and conversion methods the scale was found not to concur with the HRSD-17 in categorising the severity of depressive symptoms.

Is there evidence for aetiologically distinct subgroups of idiopathic congenital talipes equinovarus? A case-only study and pedigree analysis.

BACKGROUND: Idiopathic congenital talipes equinovarus (CTEV) is a common developmental foot disorder, the aetiology of which remains largely unknown. Some aspects of the epidemiology suggest the possibility of aetiologically distinct subgroups. Previous studies consider CTEV as a homogenous entity which may conceal risk factors in particular subgroups. We investigate evidence for aetiologically distinct subgroups of CTEV. METHODS: Parents of 785 probands completed a postal questionnaire. Family pedigrees were compiled by telephone. Case-only analysis was used to investigate interactions between risk factors and sex of the proband, CTEV laterality and CTEV family history. RESULTS: The male:female ratio was 2.3:1, 58% of probands were affected bilaterally and 11% had a first-second degree family history. There were modest interactions between family history and twin births (multivariate case - only odds ratio [ORca] = 3.87, 95%CI 1.19-12.62) and family history and maternal use of folic acid supplements in early pregnancy (ORca = 0.62, 95%CI 0.38-1.01); and between sex of the proband and maternal alcohol consumption during pregnancy (female, positive history and alcohol consumed: ORca = 0.33, 95%CI 0.12-0.89). Previous reports of an interaction between maternal smoking and family history were not confirmed. Relatives of female probands were affected more often than relatives of male probands. CONCLUSIONS: These results provide tentative evidence for aetiologically distinct CTEV subgroups. They support the 'Carter effect', suggesting CTEV develops though a multifactorial threshold model with females requiring a higher risk factor 'load', and suggest areas where future aetiological investigation might focus. Large multi-centre studies are needed to further advance understanding of this common condition.

The C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR), maternal use of folic acid supplements, and risk of isolated clubfoot: A case-parent-triad analysis.

Worldwide, 1-4 per 1,000 births are affected by clubfoot. Clubfoot etiology is unclear, but both genetic and environmental factors are thought to be involved. Low folate status in pregnant women has been implicated in several congenital malformations, and folate metabolism may be affected by polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR). Using a case-parent-triad design, the authors investigated whether the MTHFR C677T polymorphism, and maternal periconceptional folic acid supplement use, influenced risk of isolated clubfoot. Three hundred seventy-five United Kingdom case-parent triads were recruited in 1998-1999. Among the children, there was a significant trend of decreasing clubfoot risk with increasing number of T alleles: relative risk for CT vs. CC = 0.75, 95% confidence interval: 0.57, 0.97; relative risk for TT vs. CC = 0.57, 95% confidence interval: 0.35, 0.91; p trend = 0.006. This association was not modified by maternal folic acid use. Maternal MTHFR genotype did not influence clubfoot risk for the offspring overall, although a possible interaction with folic acid use was found. This is the first known report of a specific genetic polymorphism associated with clubfoot. The direction of the association is intriguing and suggests that DNA synthesis may be relevant in clubfoot development. However, clubfoot mechanisms are poorly understood, and the folate metabolism pathway is complex. Further research is needed to elucidate these relations.

Maternal medication use and the risk of brain tumors in the offspring: the SEARCH international case-control study.

N-nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R(1)NNO.COR(2)), a type of NOC, are potent neuro-carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case-control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (< or =5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case-control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring.