Manitoba Health

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

BACKGROUND: Reverse-transcription polymerase chain reaction (RT-PCR) has become the primary method to diagnose viral diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RT-PCR detects RNA, not infectious virus; thus, its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT), and infectivity in cell culture. METHODS: In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR-confirmed positive samples and determined their ability to infect Vero cell lines. RESULTS: Ninety RT-PCR SARS-CoV-2-positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median tissue culture infectious dose/mL was 1780 (interquartile range, 282-8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT, and Ct demonstrated an odds ratio (OR) for positive viral culture of 0.64 (95% confidence interval [CI], .49-.84; P < .001) for every 1-unit increase in Ct. Area under the receiver operating characteristic curve for Ct vs positive culture was OR, 0.91 (95% CI, .85-.97; P < .001), with 97% specificity obtained at a Ct of > 24. CONCLUSIONS: SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct < 24 and STT < 8 days. Infectivity of patients with Ct > 24 and duration of symptoms > 8 days may be low. This information can inform public health policy and guide clinical, infection control, and occupational health decisions. Further studies of larger size are needed.

BACKGROUND: The objective of the current study was to determine the incidence of cancer among persons with inflammatory bowel disease (IBD) and to compare these incidence rates with those of the non-IBD population using population-based data from the administrative claims data of Manitoba's universal provincial insurance plan (Manitoba Health). METHODS: IBD patients were matched 1:10 to randomly selected members of the population without IBD based on year, age, gender, and postal area of residence. The incidence of cancer was determined by linking records from the IBD and non-IBD cohorts with the comprehensive Cancer Care Manitoba registry. Incidence rates and rate ratios (IRR) were calculated based on person-years of follow-up (Crohn's disease = 21,340 person-years and ulcerative colitis [UC] = 19,665 person-years) for 1984-1997. RESULTS: There was an increased IRR of colon carcinoma for both Crohn disease patients (2.64; 95% confidence interval [95% CI], 1.69-4.12) and UC patients (2.75; 95% CI, 1.91-3.97). There was an increased IRR of rectal carcinoma only among patients with UC (1.90; 95% CI, 1.05-3.43) and an increased IRR of carcinoma of the small intestine only in Crohn disease patients (17.4; 95% CI, 4.16-72.9). An increased IRR of extraintestinal tumors was observed only for the liver and biliary tract in both Crohn disease patients (5.22; 95% CI, 0.96-28.5) and UC patients (3.96; 95% CI, 1.05-14.9). There was an increased IRR of lymphoma for males with Crohn disease only (3.63; 95% CI, 1.53-8.62), and this finding did not appear to be related to use of immunomodulatory therapy. Compared with controls, Crohn's disease was associated with an increased risk of cancer overall, but UC was not. CONCLUSIONS: There appear to be similar increased risks for developing colon carcinoma and hepatobiliary carcinoma among patients with Crohn disease and UC. There is an increased risk of developing rectal carcinoma in UC patients, an increased risk of developing carcinoma of the small bowel in Crohn disease patients, and an increased risk of developing lymphoma among males with Crohn disease.

OBJECTIVE: The aim of this study was to determine the prevalence of the major extraintestinal manifestations of inflammatory bowel disease (IBD) and their relation to disease diagnosis and gender. METHODS: We used the population-based University of Manitoba IBD Database, which includes longitudinal files on all subjects of all health system contacts identified by International Classification of Diseases, 9th Revision, Clinical Modification codes for visit diagnosis. We extracted a cohort from our database, which included subjects with a known diagnosis of IBD for at least 10 yr. We then determined how many contacts each subject had for each of the following extraintestinal IBD-associated immune diseases: primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, and erythema nodosum. We calculated the prevalence of the extraintestinal diseases using an administrative definition of having at least five health system contacts for the diagnosis in question. This administrative definition has previously been validated in Crohn's disease and ulcerative colitis (UC). RESULTS: A total of 6.2% of patients with IBD had one of six major extraintestinal diseases studied in this report. Only 0.3% of patients had multiple extraintestinal diseases. Iritis/uveitis was the most common extraintestinal disease of all assessed (2.2% of women and 1.1% of men). Iritis/uveitis was more common among women, particularly those with UC (3.8%). Primary sclerosing cholangitis was most common among men with UC (3%). Ankylosing spondylitis was more common among men, and the highest rate was seen among men with Crohn's disease (2.7%). Pyoderma gangrenosum was more common in Crohn's (1.2%) with no gender predilection. Erythema nodosum was similarly present in Crohn's and UC but was more common among women (1.9%). CONCLUSIONS: The associations of immune mediated diseases in extraintestinal sites may help us to further our understanding of IBD pathogenesis, and it may help us in developing a paradigm of disease subsets.

The aim of this study was to assess the accuracy and utility of administrative health data in identifying persons with inflammatory bowel disease on a population basis and to determine the incidence and prevalence of this disease in the Canadian province of Manitoba. The data from Manitoba Health (the province's single insurer) were used to identify residents with physician and/or hospital contacts for Crohn's disease or ulcerative colitis based on International Classification of Diseases, Ninth Revision, Clinical Modification, codes between 1984 and 1995. Of 5,182 eligible individuals, 4,514 were mailed questionnaires and 2,725 responded. Cases were defined as individuals with five or more separate medical contacts with one of these diagnoses or three or more such contacts if they were resident for less than 2 years. The accuracy of the study case definitions was high when compared with either self-report or chart review. The 1989-1994 age- and sex-adjusted annual incidence was 14.6/100,000 for Crohn's disease and 14.3/100,000 for ulcerative colitis. The prevalence of Crohn's disease in 1994 was 198.5/100,000, and that of ulcerative colitis was 169.7/100,000. In conclusion, the authors have successfully established and validated a population-based database of inflammatory bowel disease based on administrative data. The high incidence rates and dynamic epidemiology of inflammatory bowel disease in Manitoba indicate the presence of important environmental risk factors, which warrants further investigation.

While there has been a great deal of speculation over the years on the importance of emotional factors in inflammatory bowel disease (IBD), it is only in the last decade or so that studies with stronger designs have been available to clarify the nature of this relationship. This review considers recent evidence on the prevalence of anxiety and depressive disorders in IBD, the role of these disorders as a risk factor for IBD onset, the degree to which they affect the course of the IBD, and the contribution of corticosteroid treatment to psychiatric symptom onset. There is evidence that anxiety and depression are more common in patients with IBD and that the symptoms of these conditions are more severe during periods of active disease. The few studies that address the issue of anxiety and depression as risk factors for IBD do not yet provide enough information to support definite conclusions. There is evidence, however, that the course of the disease is worse in depressed patients. Treatment with corticosteroids can induce mood disorders or other psychiatric symptoms. The second part of the review focuses on patient management issues for those with comorbid anxiety or depression. Practical approaches to screening are discussed, and are recommended for routine use in the IBD clinic, especially during periods of active disease. We review evidence-based pharmacological and psychological treatments for anxiety and depression and discuss practical considerations in treating these conditions in the context of IBD to facilitate overall management of the IBD patient.

BACKGROUND: Nationally representative Canadian data on the prevalence of child abuse and its relation with mental disorders are lacking. We used contemporary, nationally representative data to examine the prevalence of 3 types of child abuse (physical abuse, sexual abuse and exposure to intimate partner violence) and their association with 14 mental conditions, including suicidal ideation and suicide attempts. METHODS: We obtained data from the 2012 Canadian Community Health Survey: Mental Health, collected from the 10 provinces. Respondents aged 18 years and older were asked about child abuse and were selected for the study sample (n = 23,395). The survey had a multistage stratified cluster design (household response rate 79.8%). RESULTS: The prevalence of any child abuse was 32% (individual types ranged from 8% to 26%). All types of child abuse were associated with all mental conditions, including suicidal ideation and suicide attempts, after adjustment for sociodemographic variables (adjusted odds ratios ranged from 1.4 to 7.9). We found a dose-response relation, with increasing number of abuse types experienced corresponding with greater odds of mental conditions. Associations between child abuse and attention deficit disorder, suicidal ideation and suicide attempts showed stronger effects for women than men. INTERPRETATION: We found robust associations between child abuse and mental conditions. Health care providers, especially those assessing patients with mental health problems, need to be aware of the relation between specific types of child abuse and certain mental conditions. Success in preventing child abuse could lead to reductions in the prevalence of mental disorders, suicidal ideation and suicide attempts.

STUDY DESIGN: Cross-section observational study of incident spinal fractures using an administrative data-base. OBJECTIVES: To identify and define all patients who have spinal fractures within a complete population. SUMMARY OF BACKGROUND DATA: The true incidence of spinal column and cord injury is not known. Previous studies have been institutional or practice based. Accurate information concerning the magnitude of the spinal injury population and their characteristics may provide more rational basis for public health decision making and resource allocation. METHODS: The study dates were April 1, 1981 to March 31, 1984. Using the Manitoba Health Services Insurance Plan database, all patients with ICD-9-CM coding of 805.x and 806.x (spinal column fracture with and without spinal cord injury) were identified. Incidence rates, age and gender distribution, and ambulatory and hospital contracts were identified. Hospital discharge abstracts were used to classify mechanisms of injury, associated injuries, and length of stay. RESULT: The annual incidence rate of spinal fracture was 64 per 100,000. Two thousand sixty-three patients were identified, with 944 being admitted to the hospital. There were two peaks of incidence occurring in young men and elderly women. Of the hospitalized patients, 182 had cervical injury, 286 had thoracic fracture, and 403 had injury in the lumbosacral spine Associated injuries occurred in 38% of hospitalized patients. Length of stay was an average of 38.5 days. Overall mortality was 41%. Neurologic injury occurred in 122 patients. CONCLUSIONS: Ambulatory care of spine injuries is more common than hospital care. Two peaks of incidence occur-in young men and elderly women. Future decisions for research, public health policy, and resource allocation can be based on these data.

BACKGROUND: The clinical significance of the high prevalence of osteopenia in inflammatory bowel disease is unclear. OBJECTIVE: To determine whether persons with inflammatory bowel disease have increased incidence of fracture. DESIGN: Population-based matched cohort study. SETTING: Manitoba, Canada. PATIENTS: Patients with inflammatory bowel disease in the University of Manitoba IBD Database (n = 6027) were matched to 10 randomly selected persons in the general population without inflammatory bowel disease (n = 60 270) by year, age, sex, and postal area of residence. MEASUREMENTS: The incidence of hospitalization for hip fracture was determined on the basis of hospital discharge abstracts. Outpatient medical billing records and hospital discharge abstracts were used to calculate the incidence of spine, rib, and forearm fractures. Rates were calculated on the basis of person-years of follow-up for 1984 to 1997. RESULTS: Persons with inflammatory bowel disease had significantly increased incidence of fractures at the spine (incidence rate ratio [IRR], 1.74 [95% CI, 1.34 to 2.24]; P < 0.001), hip (IRR, 1.59 [CI, 1.27 to 2.00]; P < 0.001), wrist/forearm (IRR, 1.33 [CI, 1.11 to 1.58]; P = 0.001), and rib (IRR, 1.25 [CI, 1.02 to 1.52]; P = 0.03) and of any of these fractures (IRR, 1.41 [CI, 1.27 to 1.56]; P < 0.001). CONCLUSION: The incidence of fracture among persons with inflammatory bowel disease is 40% greater than that in the general population.

BACKGROUND: The role of lipid modification in stroke prevention is controversial, although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease. METHODS AND RESULTS: To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we followed 4159 subjects with average total and LDL serum cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an infarction an average of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. Using prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke risk factors and the use of antiplatelet agents (85% of subjects in each group). Compared with placebo, pravastatin lowered total serum cholesterol by 20%, LDL cholesterol by 32%, and triglycerides by 14% and raised HDL cholesterol by 5% over the course of the trial. A total of 128 strokes (52 on pravastatin, 76 on placebo) and 216 strokes or TIAs (92 on pravastatin, 124 on placebo) were observed, representing a 32% reduction (95% CI, 4% to 52%, P=0.03) in all-cause stroke and 27% reduction in stroke or TIA (95% CI, 4% to 44%, P=0.02). All categories of strokes were reduced, and treatment effect was similar when adjusted for age, sex, history of hypertension, cigarette smoking, diabetes, left ventricular ejection fraction, and baseline total, HDL, and LDL cholesterol and triglyceride levels. There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo (2 versus 6, respectively). CONCLUSIONS: Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infarction in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy.

BACKGROUND: First-generation H(1)-antihistamines obtained without prescription are the most frequent form of self-medication for allergic diseases, coughs and colds and insomnia even though they have potentially dangerous unwanted effects which are not recognized by the general public. AIMS: To increase consumer protection by bringing to the attention of regulatory authorities, physicians and the general public the potential dangers of the indiscriminate use first-generation H(1)-antihistamines purchased over-the counter in the absence of appropriate medical supervision. METHODS: A GA(2)LEN (Global Allergy and Asthma European Network) task force assessed the unwanted side-effects and potential dangers of first-generation H1-antihistamines by reviewing the literature (Medline and Embase) and performing a media audit of US coverage from 1996 to 2008 of accidents and fatal adverse events in which these drugs were implicated. RESULTS: First-generation H(1)-antihistamines, all of which are sedating, are generally regarded as safe by laypersons and healthcare professionals because of their long-standing use. However, they reduce rapid eye movement (REM)-sleep, impair learning and reduce work efficiency. They are implicated in civil aviation, motor vehicle and boating accidents, deaths as a result of accidental or intentional overdosing in infants and young children and suicide in teenagers and adults. Some exhibit cardiotoxicity in overdose. CONCLUSIONS: This review raises the issue of better consumer protection by recommending that older first-generation H(1)-antihistamines should no longer be available over-the-counter as prescription- free drugs for self-medication of allergic and other diseases now that newer second- generation nonsedating H(1)-antihistamines with superior risk/benefit ratios are widely available at competitive prices.

Many countries are currently studying the possibility of mass vaccination against varicella. The objective of this study was to provide a comprehensive picture of the pre-vaccine epidemiology of the varicella zoster virus (VZV) to aid in the design of immunization programs and to adequately measure the impact of vaccination. Population-based data including physician visit claims, sentinel surveillance and hospitalization data from Canada and the United Kingdom were analysed. The key epidemiological characteristics of varicella and zoster (age specific consultation rates, seasonality, force of infection, hospitalization rates and inpatient days) were compared. Results show that the overall epidemiology of varicella and zoster is remarkably similar between the two countries. The major difference being that, contrary to Canada, the epidemiology of varicella seems to be changing in the United Kingdom with an important decrease in the average age at infection that coincides with a significant increase in children attending preschool. Furthermore, differences exist in the seasonality between the United Kingdom and Canada, which seem to be primarily due to the school calendar. These results illustrate that school and preschool contact patterns play an important role in the dynamics of varicella. Finally, our results provide baseline estimates of varicella and zoster incidence and morbidity for VZV vaccine effectiveness and cost-effectiveness studies.

BACKGROUND: Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses. METHODS/FINDINGS: Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine-lineage) viruses. CONCLUSIONS: These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.

BACKGROUND: The comorbidity of mood and anxiety disorders (MD and AD) with substance use disorders (SUD) is common. One explanation for this comorbidity is the self-medication hypothesis, which posits that individuals with MD or AD use substances to cope with the difficult symptoms associated with the disorder. Over time, self-medication (SM) can develop into an independent SUD. This narrative review will present the prevalence and correlates of SM with alcohol and/or drugs for MD and AD and the relationship between SM and subsequent SUD using both cross-sectional and longitudinal epidemiological data. METHODS: Scopus and PsycINFO were searched from January 1997 to April 2018 to identify original research articles that examined the prevalence and correlates of SM and the temporal relationship between MD/AD and SUD in the general population (n = 22). RESULTS: The prevalence of SM with alcohol and/or drugs among those with MD or AD ranged from 21.9% to 24.1%. Male sex, younger age, being separated, divorced or widowed, and being Caucasian were characteristics associated with higher proportions of respondents endorsing SM with alcohol/drugs for MD and AD. Longitudinal data supports the temporal onset of primary MD/AD and secondary SUD among those who self-report SM. CONCLUSION: Providing and promoting alternate coping strategies for those with MD/AD may reduce SM, the development of SUD, and the comorbidity of MD/AD with SUD. The concurrent treatment of MD/AD and substance use is the current "gold standard" model of care, and the results of this review support its use.

Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately. The results reveal that achieving a reduction in the contact rate between susceptible and diseased individuals by isolating the latter is a critically important strategy that can control SARS outbreaks with or without quarantine. An optimal isolation programme entails timely implementation under stringent hygienic precautions defined by a critical threshold value. Values below this threshold lead to control, but those above are associated with the incidence of new community outbreaks or nosocomial infections, a known cause for the spread of SARS in each region. Allocation of resources to implement optimal isolation is more effective than to implement sub-optimal isolation and quarantine together. A community-wide eradication of SARS is feasible if optimal isolation is combined with a highly effective screening programme at the points of entry.

BACKGROUND: Comorbidity is an area of increasing interest in multiple sclerosis (MS). OBJECTIVE: The objective of this review is to estimate the incidence and prevalence of comorbidity in people with MS and assess the quality of included studies. METHODS: We searched the PubMed, SCOPUS, EMBASE and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles. Two reviewers independently screened abstracts. One reviewer abstracted data using a standardized form and the abstraction was verified by a second reviewer. We assessed study quality using a standardized approach. We quantitatively assessed population-based studies using the I² statistic, and conducted random-effects meta-analyses. RESULTS: We included 249 articles. Study designs were variable with respect to source populations, case definitions, methods of ascertainment and approaches to reporting findings. Prevalence was reported more frequently than incidence; estimates for prevalence and incidence varied substantially for all conditions. Heterogeneity was high. CONCLUSION: This review highlights substantial gaps in the epidemiological knowledge of comorbidity in MS worldwide. Little is known about comorbidity in Central or South America, Asia or Africa. Findings in North America and Europe are inconsistent. Future studies should report age-, sex- and ethnicity-specific estimates of incidence and prevalence, and standardize findings to a common population.

An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole-exome sequencing (WES), are identifying the genetic basis of disease for 25-40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation-wide effort to identify mutations for childhood-onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases.

Individual serum concentrations of FSH, “hCG-LH,” testosterone (T) and estradiol-17β (E2) were measured by radioimmunoassay in 46 male and 33 female human fetuses delivered by hysterotomy. Results were correlated with crownrump (CR) length and maternal serum concentrations of FSH, “hCG-LH” and E2. CR-lengths ranged from 4.2 to 24.0 cm corresponding to 9–25 weeks fetal age. Serum T levels in males (40–580 ng/100 ml) were significantly higher than those in females (< 20–130 ng/100 ml). A pattern in male serum T levels similar to that we have previously reported in testicular T concentrations was seen, with the highest values at 11–17 weeks fetal age (7–15.5 cm CR length) and a subsequent decline. Fetal serum E2 concentrations varied over a wide range (<20–>800 ng/100 ml) in both sexes, but showed no apparent relationship to CR length. Overall mean E2 levels in the females were higher than in the males. Both fetal and maternal “hCG-LH” levels declined with fetal age, with no apparent sex difference. The mean maternal-fetal “hCG-LH” ratio in paired samples was 31:1. The mean fetal serum “hCG-LH” concentration was significantly higher than in the newborn. There was a temporal relationship of high “hCG-LH” levels to the elevation of T concentration in sera of male fetuses. Serum FSH levels in the males were low or undetectable, but high FSH concentrations (8–240 μg/100 ml) were found in the females. These data provide further evidence for testicular T secretion at the time of genital differentiation, and suggest that the fetal Leydig cells are stimulated primarily by chorionic rather than pituitary gonadotropin at this critical time. On the other hand, ovarian follicular development appears to depend upon fetal pituitary gonadotropin secretion.

The in vitro activities of numerous antimicrobials against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis from patients with bloodstream and respiratory tract infections in the United States, Canada, Europe, Latin America, and the Asia-Pacific region were studied in the SENTRY Antimicrobial Surveillance Program. Penicillin resistance (minimum inhibitory concentration, > or =2 microg/mL) was noted in all 5 geographic regions, and a high and increasing rate of macrolide resistance among S. pneumoniae isolates was observed. Elevated rates of resistance to clindamycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline were seen. beta-Lactamase-mediated resistance in H. influenzae to amoxicillin and variable trimethoprim-sulfamethoxazole resistance by region were documented. Resistance to several drugs continues to emerge among pneumococci worldwide, but more stable resistance patterns have been noted for H. influenzae and M. catarrhalis. Continued surveillance of this pathogen group appears to be prudent.

PURPOSE: To evaluate the sensitivity and specificity of biphasic computed tomography (CT) with mesenteric CT angiography in the diagnosis of acute mesenteric ischemia (AMI). MATERIALS AND METHODS: Sixty-two patients with clinically suspected AMI underwent prospective imaging with biphasic multi-detector row CT. Mesenteric CT angiography was performed with 1.25-mm collimation starting 25 seconds after 140 mL of intravenous contrast agent was administered at a rate of 4 mL/sec, followed by portal venous phase imaging with 5-mm collimation and a 60-70-second delay. CT angiograms were reconstructed with multiplanar (including transverse), maximum intensity projection, and volume-rendered techniques. All scans were evaluated prospectively by two independent radiologists for CT evidence of ischemia. AMI was confirmed with surgical or pathologic proof in 25 of 26 patients. In one patient, AMI was confirmed with clinical findings and serial CT examinations. In patients with AMI, sensitivity and specificity of each CT sign were calculated retrospectively by using patients who did not have intestinal ischemia as a control group. CT criteria that optimized sensitivity and specificity for the diagnosis of AMI were then developed. RESULTS: AMI was diagnosed in 26 patients. The CT angiogram depicted arterial disease in eight patients and altered care in five. A finding of any one of pneumatosis intestinalis, venous gas, superior mesenteric artery occlusion, celiac and inferior mesenteric artery occlusion with distal SMA disease, or arterial embolism was 100% specific but only 73% sensitive. Alternatively, a finding of bowel wall thickening in addition to focal lack of bowel wall enhancement, solid organ infarction, or venous thrombosis was 50% sensitive and 94% specific. By using either of these criteria for the diagnosis, a sensitivity of 96% and a specificity of 94% can be achieved. CONCLUSION: Biphasic CT with mesenteric CT angiography is effective in the diagnosis of AMI.