Factors related with symptom duration until diagnosis and treatment of symptomatic colorectal cancer

[Abstract] Background: Colorectal cancer (CRC) survival depends mostly on stage at the time of diagnosis. However, symptom duration at diagnosis or treatment have also been considered as predictors of stage and survival. This study was designed to: 1) establish the distinct time-symptom duration intervals; 2) identify factors associated with symptom duration until diagnosis and treatment. Methods: This is a cross-sectional study of all incident cases of symptomatic CRC during 2006-2009 (795 incident cases) in 5 Spanish regions. Data were obtained from patients' interviews and reviews of primary care and hospital clinical records. Measurements: CRC symptoms, symptom perception, trust in the general practitioner (GP), primary care and hospital examinations/visits before diagnosis, type of referral and tumor characteristics at diagnosis. Symptom Diagnosis Interval (SDI) was calculated as time from first CRC symptoms to date of diagnosis. Symptom Treatment Interval (STI) was defined as time from first CRC symptoms until start of treatment. Nonparametric tests were used to compare SDI and STI according to different variables. Results: Symptom to diagnosis interval for CRC was 128 days and symptom treatment interval was 155. No statistically significant differences were observed between colon and rectum cancers. Women experienced longer intervals than men. Symptom presentation such as vomiting or abdominal pain and the presence of obstruction led to shorter diagnostic or treatment intervals. Time elapsed was also shorter in those patients that perceived their first symptom/s as serious, disclosed it to their acquaintances, contacted emergencies services or had trust in their GPs. Primary care and hospital doctor examinations and investigations appeared to be related to time elapsed to diagnosis or treatment. Conclusions: Results show that gender, symptom perception and help-seeking behaviour are the main patient factors related to interval duration. Health service performance also has a very important role in symptom to diagnosis and treatment interval. If time to diagnosis is to be reduced, interventions and guidelines must be developed to ensure appropriate examination and diagnosis during both primary and hospital care.Instituto de Salud Carlos III; PI:052273Instituto de Salud Carlos III; PI050787Instituto de Salud Carlos III; PI050700Instituto de Salud Carlos III; PI052692Instituto de Salud Carlos III; PI05214

Factors related with symptom duration until diagnosis and treatment of symptomatic colorectal cancer

BACKGROUND: Colorectal cancer (CRC) survival depends mostly on stage at the time of diagnosis. However, symptom duration at diagnosis or treatment have also been considered as predictors of stage and survival. This study was designed to: 1) establish the distinct time-symptom duration intervals; 2) identify factors associated with symptom duration until diagnosis and treatment. METHODS: This is a cross-sectional study of all incident cases of symptomatic CRC during 2006–2009 (795 incident cases) in 5 Spanish regions. Data were obtained from patients’ interviews and reviews of primary care and hospital clinical records. Measurements: CRC symptoms, symptom perception, trust in the general practitioner (GP), primary care and hospital examinations/visits before diagnosis, type of referral and tumor characteristics at diagnosis. Symptom Diagnosis Interval (SDI) was calculated as time from first CRC symptoms to date of diagnosis. Symptom Treatment Interval (STI) was defined as time from first CRC symptoms until start of treatment. Nonparametric tests were used to compare SDI and STI according to different variables. RESULTS: Symptom to diagnosis interval for CRC was 128 days and symptom treatment interval was 155. No statistically significant differences were observed between colon and rectum cancers. Women experienced longer intervals than men. Symptom presentation such as vomiting or abdominal pain and the presence of obstruction led to shorter diagnostic or treatment intervals. Time elapsed was also shorter in those patients that perceived their first symptom/s as serious, disclosed it to their acquaintances, contacted emergencies services or had trust in their GPs. Primary care and hospital doctor examinations and investigations appeared to be related to time elapsed to diagnosis or treatment. CONCLUSIONS: Results show that gender, symptom perception and help-seeking behaviour are the main patient factors related to interval duration. Health service performance also has a very important role in symptom to diagnosis and treatment interval. If time to diagnosis is to be reduced, interventions and guidelines must be developed to ensure appropriate examination and diagnosis during both primary and hospital care

Phosphomannomutase deficiency (PMM2-CDG): Ataxia and cerebellar assessment

Background: Phosphomannomutase deficiency (PMM2-CDG) is the most frequent congenital disorder of glycosylation. The cerebellum is nearly always affected in PMM2-CDG patients, a cerebellar atrophy progression is observed, and cerebellar dysfunction is their main daily functional limitation. Different therapeutic agents are under development, and clinical evaluation of drug candidates will require a standardized score of cerebellar dysfunction. We aim to assess the validity of the International Cooperative Ataxia Rating Scale (ICARS) in children and adolescents with genetically confirmed PMM2-CDG deficiency. We compare ICARS results with the Nijmegen Pediatric CDG Rating Scale (NPCRS), neuroimaging, intelligence quotient (IQ) and molecular data. Methods: Our observational study included 13 PMM2-CDG patients and 21 control subjects. Ethical permissions and informed consents were obtained. Three independent child neurologists rated PMM2-CDG patients and control subjects using the ICARS. A single clinician administered the NPCRS. All patients underwent brain MRI, and the relative diameter of the midsagittal vermis was measured. Psychometric evaluations were available in six patients. The Mann-Whitney U test was used to compare ICARS between patients and controls. To evaluate inter-observer agreement in patients' ICARS ratings, intraclass correlation coefficients (ICC) were calculated. ICARS internal consistency was evaluated using Cronbach's alpha. Spearman's rank correlation coefficient test was used to correlate ICARS with NPCRS, midsagittal vermis relative diameter and IQ. Results: ICARS and ICARS subscores differed between patients and controls (p < 0.001). Interobserver agreement of ICARS was "almost perfect" (ICC = 0.99), with a "good" internal reliability (Cronbach's alpha = 0.72). ICARS was significantly correlated with the total NPCRS score (rs 0.90, p < 0.001). However, there was no agreement regarding categories of severity. Regarding neuroimaging, inverse correlations between ICARS and midsagittal vermis relative diameter (rs -0.85, p = 0.003) and IQ (rs -0.94, p = 0.005) were found. Patients bearing p.E93A, p.C241S or p.R162W mutations presented a milder phenotype. Conclusions: ICARS is a reliable instrument for assessment of PMM2-CDG patients, without significant inter-rater variability. Despite our limited sample size, the results show a good correlation between functional cerebellar assessment, IQ and neuroimagingFor the first a correlation between ICARS, neuroimaging and IQ in PMM2-CDG patients has been demonstratedThe work was supported by national grants PI14/00021, PI11/01096, PI11/01250, and PI10/00455 from the National Plan on I+D+I, cofinanced by ISC-III (Subdirección General de Evaluación y Fomento de la Investigación Sanitaria) and FEDER (Fondo Europeo de Desarrollo Regional) and IPT-2012- 0561-010000 from MINECO. Three research groups (U-746, U-737 and U703) from the Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Spain, have worked together for the present stud

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Phosphomannomutase deficiency (PMM2-CDG) : ataxia and cerebellar assessment

Phosphomannomutase deficiency (PMM2-CDG) is the most frequent congenital disorder of glycosylation. The cerebellum is nearly always affected in PMM2-CDG patients, a cerebellar atrophy progression is observed, and cerebellar dysfunction is their main daily functional limitation. Different therapeutic agents are under development, and clinical evaluation of drug candidates will require a standardized score of cerebellar dysfunction. We aim to assess the validity of the International Cooperative Ataxia Rating Scale (ICARS) in children and adolescents with genetically confirmed PMM2-CDG deficiency. We compare ICARS results with the Nijmegen Pediatric CDG Rating Scale (NPCRS), neuroimaging, intelligence quotient (IQ) and molecular data. Our observational study included 13 PMM2-CDG patients and 21 control subjects. Ethical permissions and informed consents were obtained. Three independent child neurologists rated PMM2-CDG patients and control subjects using the ICARS. A single clinician administered the NPCRS. All patients underwent brain MRI, and the relative diameter of the midsagittal vermis was measured. Psychometric evaluations were available in six patients. The Mann-Whitney U test was used to compare ICARS between patients and controls. To evaluate inter-observer agreement in patients' ICARS ratings, intraclass correlation coefficients (ICC) were calculated. ICARS internal consistency was evaluated using Cronbach's alpha. Spearman's rank correlation coefficient test was used to correlate ICARS with NPCRS, midsagittal vermis relative diameter and IQ. ICARS and ICARS subscores differed between patients and controls (p < 0.001). Interobserver agreement of ICARS was "almost perfect" (ICC = 0.99), with a "good" internal reliability (Cronbach's alpha = 0.72). ICARS was significantly correlated with the total NPCRS score (r 0.90, p < 0.001). However, there was no agreement regarding categories of severity. Regarding neuroimaging, inverse correlations between ICARS and midsagittal vermis relative diameter (r −0.85, p = 0.003) and IQ (r −0.94, p = 0.005) were found. Patients bearing p.E93A, p.C241S or p.R162W mutations presented a milder phenotype. ICARS is a reliable instrument for assessment of PMM2-CDG patients, without significant inter-rater variability. Despite our limited sample size, the results show a good correlation between functional cerebellar assessment, IQ and neuroimagingFor the first a correlation between ICARS, neuroimaging and IQ in PMM2-CDG patients has been demonstrated