Clinicopathological Features and Management of Cancers in Lynch Syndrome

Lynch syndrome (LS) is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC) and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS

Association of post-stroke-initiated antidepressants with long-term outcomes in young adults with ischaemic stroke

Objective We examined the association between initiation of antidepressants within the first year after ischaemic stroke (IS) in young adults and long-term fatal and non-fatal cardiovascular events, as well as all-cause mortality. Patients and methods The Helsinki Young Stroke Registry (HYSR) includes patients aged 15-49 years with their first-ever IS occurring 1994-2007. From nationwide registers, we obtained data on prescriptions (1993-2011) and outcomes of interest (1994-2011). Time of initiating post-stroke antidepressants (PSADs) was defined as time of the first filled prescription for antidepressants within the first year from IS. To account for non-random assignment of PSADs, we performed propensity score matching and studied the relationship between PSAD initiation and outcomes using Cox regression models with time-varying coefficients. Results Of all patients (n = 888), 206 (23.2%) initiated PSADs within the first year, of which 203 (98.5%) could be matched to 406 non-initiators. In this matched sample of 609 patients, the median follow-up time was 8.1 (interquartile range [IQR] 5.0-12.6) years and 169 (28.9%) patients had any cardiovascular events, 95 (15.8%) had recurrent ischaemic or haemorrhagic strokes and 106 (17.4%) died. Adjusted for sociodemographics and cardiovascular comorbidities, PSAD initiation was associated with recurrent ischaemic or haemorrhagic stroke 5-10 years after IS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.32-7.12). No association emerged between PSAD initiation and other outcomes. Conclusions In young adults, PSAD initiation within the first year after IS was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Future studies are needed to verify the results and to further study the nature of this finding. KEY MESSAGES Initiation of post-stroke antidepressants (PSADs) within the first year after ischaemic stroke (IS) was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Patients starting antidepressants after IS should be followed up more closely in case of recurrent events. Future studies are needed to verify the results and to further study the nature of this finding.Peer reviewe

Initiation of antidepressants in young adults after ischemic stroke: a registry-based follow-up study

cited By 0Objective Data on post-stroke use of antidepressants in young individuals are scarce. We examined pattern and factors associated with initiating post-stroke antidepressants (PSAD) after ischemic stroke (IS) in young adults. Methods Helsinki Young Stroke Registry includes patients aged 15-49 years with first-ever IS, 1994-2007. Data on prescriptions, hospitalizations and death came from nationwide registers. We defined time of initiating PSAD as time of the first filled prescription for antidepressants within 1 year from IS. We assessed factors associated with initiating PSAD with multivariable Cox regression models, allowing for time-varying effects when appropriate. Results We followed 888 patients, of which 206 (23.2%) initiated PSAD. Higher hazard of starting PSAD within the first 100 days appeared among patients with mild versus no limb paresis 2.53 (95% confidence interval 1.48-4.31) and during later follow-up among those with silent infarcts (2.04; 1.27-3.28), prior use of antidepressants (2.09; 1.26-3.46) and moderate versus mild stroke (2.06; 1.18-3.58). The relative difference in the hazard rate for moderate-severe limb paresis persisted both within the first 100 days (3.84, 2.12-6.97) and during later follow-up (4.54; 2.51-8.23). The hazard rate was higher throughout the follow-up among smokers (1.48; 1.11-1.97) as well as lower (1.78; 1.25-2.54) and upper white-collar workers (2.00; 1.24-3.23) compared to blue-collar workers. Conclusion One-fourth of young adults started PSADs within 1 year from IS. We identified several specific clinical characteristics associated with PSAD initiation, highlighting their utility in assessing the risk of post-stroke depression during follow-up.Peer reviewe

Use of antihypertensive medication after ischemic stroke in young adults and its association with long-term outcome

Background: Knowledge on the use of secondary preventive medication in young adults is limited. Methods: We included 936 first-ever ischemic stroke 30-day survivors aged 15-49, enrolled in the Helsinki Young Stroke Registry, 1994-2007. Follow-up data until 2012 came from Finnish Care Register, Statistics Finland, and Social Insurance Institution of Finland. Usage thresholds were defined as non-users, low (prescription coverage 80%). Adjusted Cox regression allowed assessing the association of usage with all-cause mortality and recurrent vascular events. Results: Of our patients, 40.5% were non-users, 7.8% had low usage, 11.8% intermediate usage and 40.0% high usage. Median follow-up was 8.3 years. Compared to non-users, risk of mortality and recurrent stroke or TIA was lower for patients with low-intermediate (HR 0.40, 95% CI 0.22-0.65; HR 0.31, 95% CI 0.18-0.53) and high usage (HR 0.25, 95% CI 0.15-0.42; HR 0.30, 95% CI 0.19-0.46), after adjustment for confounders. Conclusions: Use of antihypertensives was suboptimal in one-third of patients in whom antihypertensives were initially prescribed. Users were at lower risk of mortality and recurrent stroke or TIA compared to non-users.Key Messages The use of antihypertensive medication is suboptimal in one-third of patients in whom antihypertensive medication was initially prescribed after ischemic stroke at young age. The risk of mortality and recurrent stroke or TIA is lower for users of antihypertensive medication after ischemic stroke at young age compared to non-users, after adjustment for relevant confounders including pre-existing hypertension and prior use of antihypertensive medication. Specific guidelines on antihypertensive medication use after ischemic stroke at young age are lacking. However, our results may motivate doctors and patients in gaining better usage of antihypertensive medication, since better usage was associated with more favorable outcome in this study.Peer reviewe

Long-term persistence of withdrawal of temazepam, zopiclone, and zolpidem in older adults: a 3-year follow-up study

Background: Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications.Methods: 92 outpatients (>= 55 years) with primary insomnia, long-term BZDA use as hypnotics (mean duration of BZDA use 9.9 +/- 6.2 years), and willingness to withdraw from BZDAs each received either melatonin or a placebo nightly for one month. During this period, BZDAs were meant to be gradually withdrawn. Sleep hygiene counselling and psychosocial support were provided. Three years later, use of BZDAs and other medications was determined by interview and confirmed from medical records.Results: Of the original 92 outpatients, 83 (90%) participated in the 3-year survey (mean follow-up 3.3 +/- 0.2 years). The number of BZDA-free participants decreased from 34 (37%) at 6 months to 26 (28%; intention-to-treat) at 3 years, that of irregular BZDA users decreased from 44 (48%) at 6 months to 27 (29%) at 3 years, while that of regular users increased from 11 (12%) at 6 months to 30 (33%) at 3 years (P = 0.001). Those who were regular BZDA users at 3 years had at baseline (before withdrawal) higher BMI (P = 0.001) than did other participants. At 3 years, the total number of medications remained unchanged for non-users (P = 0.432), but increased for the irregular (P = 0.011) and regular users (P = 0.026) compared to baseline. At 3 years, compared to baseline, use of antidepressants, dopamine agonists, melatonin, and NSAIDs/paracetamol was significantly more common in the whole cohort, but their use did not differ between the BZDA-user subgroups. Randomization to melatonin or placebo during BZDA withdrawal was unrelated to BZDA-withdrawal result.Conclusions: At 3 years after withdrawal, the number of BZDA-free participants had decreased, but still one-third of the subjects remained BZDA-free, and one-third had reduced their use. Successful BZDA withdrawal did not lead to any increase in total number of medications; use of symptomatic medications in the whole cohort, however, did increase

Cost analysis of antibiotic therapy versus appendectomy for treatment of uncomplicated acute appendicitis: 5-year results of the APPAC randomized clinical trial

BackgroundThe efficacy and safety of antibiotic treatment for uncomplicated acute appendicitis hasbeen established at long-term follow-up with the majority of recurrences shown to occurwithin the first year. Overall costs of antibiotics are significantly lower compared with appendectomyat short-term follow-up, but long-term durability of these cost savings is unclear.The study objective was to compare the long-term overall costs of antibiotic therapy versusappendectomy in the treatment of uncomplicated acute appendicitis in the APPAC (APPendicitisACuta) trial at 5 years.Methods and findingsThis multicentre, non-inferiority randomized clinical trial randomly assigned 530 adultpatients with CT-confirmed uncomplicated acute appendicitis to appendectomy or antibiotictreatment at six Finnish hospitals. All major costs during the 5-year follow-up were recorded,whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis.Between November 2009 and June 2012, 273 patients were randomized to appendectomyand 257 to antibiotics. The overall costs of appendectomy were 1.4 times higher(pCI: €3879 to €4463) resulting in cost savings of €1545 per patient (95% CI: €1193 to €1899;ppatients did not undergo appendectomy.ConclusionsAt 5-year follow-up antibiotic treatment resulted in significantly lower overall costs comparedwith appendectomy. As the majority of appendicitis recurrences occur within the first yearafter the initial antibiotic treatment, these results suggest that treating uncomplicated acuteappendicitis with antibiotics instead of appendectomy results in lower overall costs even atlonger-term follow-up.</p

Sosiaalinen verkkopalvelu mobiiliksi : tapaus Wreckamovie.com

Opinnäytetyön aiheena on verkkopalvelun mobiiliversion suunnittelu. Työn toiminnallisena osana suunniteltiin ja toteutettiin yhteisöllisen elokuvatuotantopalvelun Wreckamovie.comin mobiiliversio, joka löytyy osoitteesta http://www.wreckamovie.com. Kirjallisessa osassa dokumentoidaan toiminnallisen osan työvaiheita ja ratkaisuja sekä työskentelyssä käytettyjä työmenetelmiä ja kehitysympäristöä. Siinä käydään läpi kohdelaitteet ja niiden selaimet sekä painotetaan mobiililaitteiden yleistymistä web-selainlaitteena ja kuinka siihen tulisi suhtautua. Työ tehtiin Star Wreck Studios Oy:n toimeksiantona. Yksityiskohtaisella tasolla se tukee Ruby on Rails sovelluskehyksellä rakennettujen sivustojen mobiiliversioiden kehittämistä. Se on kuitenkin suunnattu kaikille mobiililaitteet huomioonottavasta web-kehityksestä kiinnostuneille. Työ pyrkii motivoimaan mobiililaitteiden huomioimiseen web-kehityksessä ja käy läpi erilaisia lähtökohtia ja ajattelutapoja mobiilisuunnitteluun. Työssä myös tarkastellaan mitä hyötyjä koko kehitettävän palvelun kannalta voidaan saavuttaa suunnittelemalla se mobiililaitteiden rajoitusten ehdoilla nk. mobiili edellä -suunnittelutavan mukaisesti. Lisäksi työ avaa responsiivisen web-suunnittelun käsitettä, jonka periaatteena on rakentaa web-sivun sommitelma mukautumaan sitä näyttävän laitteen ominaisuuksien kannalta parhaalla mahdollisella tavalla. Suunnittelutavasta annetaan perustavanlaatuisia kooditason esimerkkejä, jotka vaativat lukijalta ainoastaan HTML- ja CSS-ymmärrystä. Työssä käydään myös läpi mobiililaitteen tunnistaminen Ruby on Rails -sovelluskehyksen avulla ja kerrotaan, mitä eri tapoja on toteuttaa sivustolle mobiiliversio. Työn tärkeäksi johtopäätökseksi nousi se, että web-palvelu tulisi kehittää niin, että sen käytettävyys ja suorituskyky olisivat optimaalisia aina sitä selaavalle laitteelle. Tämä on päällimmäisenä ajatuksena responsiivisen suunnittelun ajattelutavassa, jota voidaan pitää tulevaisuuden mallina web-suunnittelulle.The topic of this thesis deals with designing a mobile optimized website. It was carried out as an assignment of Star Wreck Studios Oy. The functional part of the thesis consisted of designing and building a mobile and thus optimized version of the social filmmaking website Wreckamovie.com. The solutions made in different stages of the functional part are documented in the literary part. It also includes the practices used and the development environments, and takes a look at the target devices outlined in the assignment. It emphasizes the growth of mobile as a web access device and shows ways to react to it. In a detailed level, the thesis will support the development of web sites by giving basic code examples. The applied web application framework is called Ruby on Rails. However, it is aimed for everyone interested in mobile optimized web design. The aim of the thesis is to motivate the web designer to take the mobile devices into account in their design. It takes a look at different styles and views of designing for mobile such as designing Mobile First. It shows what kinds of benefits may be achieved by designing a website embracing the constraints of mobile devices, rather than fighting them. The thesis also covers the concept of Responsive Web Design and gives code examples of it. Its’ principle is to design a web page to adapt to the media that renders it with the help of media queries and flexible grids. The main conclusion of the thesis is that the web service should be developed in such way, that both its usability and performance are always optimized to the device rendering it. Responsive Web Design is all about that and it could be seen as the way of web design of the future