Background
A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer (CRC) screening.
Methods
We conducted a randomized controlled ...trial to evaluate the effect of flexible sigmoidoscopy screening on CRC incidence and mortality. A questionnaire to assess the eligibility and interest in screening was mailed to 236 568 men and women, aged 55-64 years, who were randomly selected from six trial centers in Italy. Of the 56 532 respondents, interested and eligible subjects were randomly assigned to the intervention group (invitation for flexible sigmoidoscopy; n = 17 148) or the control group (no further contact; n = 17 144), between June 14, 1995, and May 10, 1999. Flexible sigmoidoscopy was performed on 9911 subjects. Intention-to-treat and per-protocol analyses were performed to compare the CRC incidence and mortality rates in the intervention and control groups. Per-protocol analysis was adjusted for noncompliance.
Results
A total of 34 272 subjects (17 136 in each group) were included in the follow-up analysis. The median follow-up period was 10.5 years for incidence and 11.4 years for mortality; 251 subjects were diagnosed with CRC in the intervention group and 306 in the control group. Overall incidence rates in the intervention and control groups were 144.11 and 176.43, respectively, per 100 000 person-years. CRC-related death was noted in 65 subjects in the intervention group and 83 subjects in the control group. Mortality rates in the intervention and control groups were 34.66 and 44.45, respectively, per 100 000 person-years. In the intention-to-treat analysis, the rate of CRC incidence was statistically significantly reduced in the intervention group by 18% (rate ratio RR = 0.82, 95% confidence interval CI = 0.69 to 0.96), and the mortality rate was non-statistically significantly reduced by 22% (RR = 0.78; 95% CI = 0.56 to 1.08) compared with the control group. In the per-protocol analysis, both CRC incidence and mortality rates were statistically significantly reduced among the screened subjects; CRC incidence was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group.
Conclusion
A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality.
Purpose
The aim of this study was to establish a valid national cohort of patients diagnosed with acromegaly by combining data from the general National Patient Register (NPR) and the ...disease-specific Swedish Pituitary Register (SPR).
Methods
Patients ≥ 18 years of age at diagnosis of acromegaly reported from 1991 to 2018 who were registered in the NPR and/or SPR were included. The diagnosis of acromegaly was considered correct for patients identified in both registers or confirmed through chart review. Medical records were reviewed in two of Sweden´s six health care regions if the patient was reported only in the NPR. An algorithm for the NPR, with criteria requiring multiple diagnosis registrations and tumour and/or surgery codes, was constructed to reduce the number of patients to review in the remaining four regions.
Results
A total of 1866 patients were identified. Among these, 938 were reported in both registers. After application of the algorithm and chart review, the diagnosis was confirmed for 83 of the 906 patients found only in the NPR. Among 22 patients only registered in the SPR, a review of medical records confirmed acromegaly in 13. This resulted in a total of 1034 cases with acromegaly during the study period. The incidence rate of acromegaly in Sweden 1991–2018 was calculated to 4.0/million/year in the entire population and 5.1/million/year among subjects ≥ 18 years of age.
Conclusion
The combination of the SPR and NPR established a valid cohort of patients diagnosed with acromegaly and increased the estimated incidence in Sweden.
A hot stable field-reversed configuration (FRC) has been produced in the C-2 experiment by colliding and merging two high-β plasmoids preformed by the dynamic version of field-reversed θ-pinch ...technology. The merging process exhibits the highest poloidal flux amplification obtained in a magnetic confinement system (over tenfold increase). Most of the kinetic energy is converted into thermal energy with total temperature (T{i}+T{e}) exceeding 0.5 keV. The final FRC state exhibits a record FRC lifetime with flux confinement approaching classical values. These findings should have significant implications for fusion research and the physics of magnetic reconnection.
We demonstrate passive mode-locking by means of a semiconductor saturable-absorber mirror in a diode-pumped Yb:YLF laser. We present crystal growth process, spectroscopic measurements, and ...investigation of mode-locking performance. Pulse trains with minimum duration of 196 fs, average power of 54 mW and a repetition rate of 55 MHz were obtained. The optical spectrum, centered at 1028 nm, has a 7.1-nm bandwidth leading to nearly transform-limited pulses.
Summary
Background The insulin tolerance test (ITT) is the gold standard test to evaluate hypothalamic–pituitary–adrenal (HPA) axis in suspected ACTH insufficiency. When contraindicated, alternative ...tests have been proposed such as metyrapone and ACTH stimulation test. 250 µg ACTH is a supramaximal dose and unreliable in this setting. The diagnostic reliability of 1·0 µg ACTH test is controversial and very low doses have been proposed.
Design In 31 patients with hypothalamo–pituitary disorders and normal basal cortisol, we compared the diagnostic sensitivity, specificity and accuracy of metyrapone metyrapone test (MET) 30 mg/kg p.o., high (HDT, 250 µg i.v.), low (LDT, 1·0 µg i.v.) and very‐low (VLDT, 0·06 µg i.v.) dose ACTH tests. Receiver operator curve (ROC) analysis was applied with ITT as reference test.
Results MET approached the best pairs of values for highest sensitivity (71·4% and 64·3%) and highest specificity (100% and 82·4%) using ACTH and 11‐deoxycortisol (11‐DOC) cut‐off of 17·3 pmol/l and 144·3 nmol/l. Either HDT or LDT sensitivity approached 71·4% with a specificity of 82·4% or 73·3% with a specificity of 80% for cortisol cut‐off of 582·1 or 477·3 nmol/l. VLDT approached the highest sensitivity (57·1%) and highest specificity (88·2%) for a cortisol cut‐off of 364·2 nmol/l.
Conclusion Neither MET nor ACTH test can be considered completely reliable for the diagnosis of secondary hypoadrenalism, when compared with ITT that remains the best test. Either MET or ACTH stimulation test, at both high and low dose, show an overall similar reliability, provided that appropriated cut‐off values were considered; testing with very low ACTH doses seems to be misleading.
Aim: To evaluate the efficacy of periocular triamcinolone acetonide for the treatment of thyroid associated ophthalmopathy (TAO), and the presence of ocular or systemic adverse effects. Methods: A ...multicentre prospective pilot study was performed on patients diagnosed with Graves’ ophthalmopathy less than 6 months before entry to the study. Patients were admitted to the study and were randomised into two groups: treatment and control. The treatment group received four doses of 20 mg of triamcinolone acetate 40 mg/ml in a peribulbar injection to the inferolateral orbital quadrant. Both groups were evaluated by measuring the area of binocular vision without diplopia on a Goldmann perimeter and the size of the extraocular muscles on computed tomography (CT) scans. Ophthalmological and systemic examinations were done to rule out ocular and systemic adverse effects. Follow up was 6 months for both groups. Results: 50 patients were eligible for the study. 41 patients completed the study. There was an increase in the area of binocular vision without diplopia in the treatment group (Σ initial: mean 231.1 (SD 99.9) and final absolute change, mean 107.1 (SD 129.0)) compared to the control group (Σ initial: mean 350.7 (SD 86.5) and final absolute change, mean −4.5 (SD 67.6)). The sizes of the extraocular muscles were reduced in the treatment group (mean (inferior rectus initial values): 1.3 (0.7), final percentage change: −13.2 (25.7), medial rectus initial values: 1.2 (0.6), final percentage change: −8.2 (20.7), superior rectus-levator palpebrae initial values: 1.2 (0.6), final percentage change: −9.5 (29.1), lateral rectus initial values: 1.0 (0.4), final percentage change: −11.5 (20.6)) compared to the control group (inferior rectus initial values: 0.9 (0.3), final percentage change: −4.0 (21.5), medial rectus initial values: 0.9 (0.3), final percentage change: 0.6 (22.4), superior rectus-levator palpebrae initial values: 0.9 (0.3), final percentage change: 12.5 (37.5), lateral rectus initial values: 0.9 (0.4), final percentage change: −0.5 (31.6)). Both measurements (degree of diplopia and muscle thickness) were statistically significant between groups (initial − final). No systemic or ocular adverse effects were found. Conclusions: Triamcinolone administered as a periocular injection is effective in reducing diplopia and the sizes of extraocular muscles in TAO ophthalmopathy of recent onset. This form of treatment is not associated with systemic or ocular side effects.
Summary
We evaluated the contribution of germline CDKN2A mutations and MC1R variants to the development of melanoma in a hospital‐based study of single (SPM, n = 398) and multiple primary melanoma ...(MPM, n = 95). The overall frequency of CDKN2A mutations was 15.2%, and four‐fold higher in MPM than in SPM cases (OR = 4.27; 95% CI 2.43–7.53). The likelihood of identifying a CDKN2A mutation increased with family history of melanoma and younger age at diagnosis in MPM cases. Compared to SPM patients, the risk of harboring a CDKN2A mutation rose as the number of primary melanomas increased and was not influenced by family history. The G101W and E27X founder mutations were the most common. Several other mutations (W15X, Q50X, R58X, A68L, A127P and H142R) were detected for the first time in Italian patients. One novel mutation, T77A, was identified. Several non‐coding variants with unknown functional significance were also found (5′UTR −25C > T, −21C > T, −67G > C, IVS1 +37G > C); the novel 5′UTR −21C > T variant was not detected in controls. The CDKN2A A148T polymorphism was more frequent in MPM patients than in the control population (15.7% versus 6.6%). Compared to the SPM patients, MPM cases had a 2‐fold increased probability of being MC1R variant carriers and a higher probability of carrying two or more variants. No specific association was observed between the type of variant and the number of melanomas, suggesting that the number rather than the type of MC1R variant increases the risk of MPM. We observed no interaction between CDKN2A status and the presence of MC1R variants. The high frequency of CDKN2A mutations in our MPM cases, independent of their family history, is of relevance to genetic counseling and testing in our population.
Abstract Purpose To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA ...genetic testing. Patients and methods The probability of BRCA mutation according to the three tools was retrospectively estimated in 918 index cases consecutively undergone BRCA testing at 15 Italian cancer genetics clinics between 2006 and 2008. Results 179 of 918 cases (19.5%) carried BRCA mutations. With the strict use of the criteria based on cancer family history 173 BRCA (21.9%) mutations would have been detected in 789 individuals. At the commonly used 10% threshold of BRCA mutation carrier probability, the genetic models showed a similar performance PPV (38% and 37%), sensitivity (76% and 77%) and specificity (70% and 69%). Their strict use would have avoided around 60% of the tests but would have missed approximately 1 every 4 carriers. Conclusion Our data highlight the complexity of BRCA testing referral in routine practice and question the strict use of genetic models for BRCA risk assessment.
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