765 results on '"Clark RE"'
Search Results
2. Antisense therapeutics in chronic myeloid leukaemia: the promise, the progress and the problems
- Author
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Clark, RE
- Published
- 2000
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- View/download PDF
3. Clinical use of streptolysin-O to facilitate antisense oligodeoxyribonucleotide delivery for purging autografts in chronic myeloid leukaemia
- Author
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Clark, RE, Grzybowski, J, Broughton, CM, Pender, NT, Spiller, DG, Brammer, CG, Giles, RV, and Tidd, DM
- Published
- 1999
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- View/download PDF
4. Previous treatment predicts the efficiency of blood progenitor cell mobilisation: validation of a chemotherapy scoring system
- Author
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Clark, RE and Brammer, CG
- Published
- 1998
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5. Comparison of a patient-controlled analgesia system with continuous infusion for administration of diamorphine for mucositis
- Author
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Pillitteri, LC and Clark, RE
- Published
- 1998
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6. Preclinical studies of streptolysin-O in enhancing antisense oligonucleotide uptake in harvests from chronic myeloid leukaemia patients
- Author
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Broughton, CM, Spiller, DG, Pender, N, Komorovskaya, M, Grzybowski, J, Giles, RV, Tidd, DM, and Clark, RE
- Published
- 1997
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7. European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching
- Author
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Devergie, A, Apperley, JF, Labopin, M, Madrigal, A, Jacobsen, N, Carreras, E, Prentice, HG, Jouet, JP, Kolb, HJ, Herstenstein, B, Bacigalupo, A, Evensen, SA, Ljungman, P, de Witte, T, Reiffers, J, Nagler, A, Clark, RE, Goldman, JM, and Gratwohl, A
- Published
- 1997
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8. e19a2-positive chronic myeloid leukaemia with BCR exon e16-deleted transcripts
- Author
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Wang, L, Seale, J, Woodcock, BE, and Clark, RE
- Published
- 2002
- Full Text
- View/download PDF
9. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia
- Author
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Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM, Moiraghi B, Perez M, Greil R, Valent P, Bosly A, Martiat P, Noens L, André M, Verhoef G, Conchon M, Souza C, Nonino A, Hungria V, Zanichelli MA, Colturato V, Forrest D, Lipton JH, Savoie ML, Delage R, Lalancette M, Quintero G, Gomez M, Klamova H, Faber E, Bjerrum OW, Fredriksen H, Vestergaard H, Marcher C, Kamel H, Elzawam H, Porkka K, Remes K, Reiffers J, Guilhot F, Facon T, Tulliez M, Guerci Bresler AP, Nicolini FE, Charbonnier A, Rea D, Johnson Ansah A, Legros L, Harousseau JL, Rigal Huguet F, Escoffre M, Gardembas M, Guyotat D, Cahn JY, Gattermann N, Ottmann O, Niederwieser D, Stegelmann F, Schafhausen P, Brümmendorf T, Duyster J, Blumenstengel K, Scheid C, Kneba M, Kwong YL, Masszi T, Petrini M, Alimena G, Di Raimondo F, Rosti G, Rotoli B, Pungolino E, Amadori S, Abruzzese E, Fioritoni G, Lauria F, Bosi A, Martelli M, Rambaldi A, Ferrara F, Nobile F, Gobbi M, Carella AM, Orlandi EM, Leoni P, Tiribelli M, Levis A, Imamura M, Takahashi N, Tsukamoto N, Chiba S, Nagai T, Okamoto S, Miura O, Kurokawa M, Ohnishi K, Toba K, Nakao S, Tomita A, Miyamura K, Hino M, Maeda Y, Kimura A, Kawaguchi T, Miyazaki Y, Nakaseko C, Jinnai I, Matsuda A, Matsumura I, Ishikawa J, Ohyashiki K, Okada M, Usuki K, Kobayashi Y, Ohishi K, Imai K, Miyawaki S, Kanda Y, Park SY, Kim HJ, Sohn SK, Lee KH, Jung CW, Ong TC, Gómez Almaguer D, Kassack J, Ossenkoppele GJ, Gedde Dahl T, Hjorth Hansen H, Jedrzejczak W, Dmoszynska A, Starzak Dwozdz J, Holowiecki J, Kyrcz Krzemieñ S, Kuliczkowski K, Zaritsky A, Turkina A, Pospelova T, Goh YT, Koh LP, Demitrovicova L, Mistrik M, Ruff P, Louw V, Dreosti LM, Novitzky N, Cohen G, Cervantes F, Cañizo C, de Paz R, del Castillo S, Perez Encinas M, Sanz Alonso M, Marin F, Pérez López R, Hernandez Boluda J, Echeveste Gutierrez MA, Odriozola J, Herrera P, Steegman JL, Conde E, Lopez P, Giraldo P, Boque C, Heredia B, Font AJ, Rodriguez RF, Rodriguez MJ, Batlle J, Stenke L, Lehmann S, Wadenvik H, Simonsson B, Markevärn B, Själander A, Richter J, Bjoreman M, Eriksson KM, Chalandon Y, Shih LY, Yao M, Wang MC, Jootar S, Bunworasate U, Ulkü B, Haznedar R, Undar B, Sahin B, Marin D, Smith G, Byrne J, Holyoake T, Kalaycio M, Akard L, Heaney M, Al Janadi A, Goldberg S, Powell B, Harker WG, Shea T, Gingrich R, Glass J, Paquette R, Siegrist C, Woodson M, Fehrenbacher L, Koh H, Flinn I, Arrowsmith E, Ervin T, Guerra M, Wallach H, Berry W, Burke J, Edenfield W, Guzley G, Davis J, Richards D, Schlossman D, Kolibaba K, Alemany C, Savin M, Robbins G, Lopez J, Goldman JM, Camm J, Schiffer CA, Sargent D.J., PANE, FABRIZIO, Saglio, G, Kim, Dw, Issaragrisil, S, le Coutre, P, Etienne, G, Lobo, C, Pasquini, R, Clark, Re, Hochhaus, A, Hughes, Tp, Gallagher, N, Hoenekopp, A, Dong, M, Haque, A, Larson, Ra, Kantarjian, Hm, Moiraghi, B, Perez, M, Greil, R, Valent, P, Bosly, A, Martiat, P, Noens, L, André, M, Verhoef, G, Conchon, M, Souza, C, Nonino, A, Hungria, V, Zanichelli, Ma, Colturato, V, Forrest, D, Lipton, Jh, Savoie, Ml, Delage, R, Lalancette, M, Quintero, G, Gomez, M, Klamova, H, Faber, E, Bjerrum, Ow, Fredriksen, H, Vestergaard, H, Marcher, C, Kamel, H, Elzawam, H, Porkka, K, Remes, K, Reiffers, J, Guilhot, F, Facon, T, Tulliez, M, Guerci Bresler, Ap, Nicolini, Fe, Charbonnier, A, Rea, D, Johnson Ansah, A, Legros, L, Harousseau, Jl, Rigal Huguet, F, Escoffre, M, Gardembas, M, Guyotat, D, Cahn, Jy, Gattermann, N, Ottmann, O, Niederwieser, D, Stegelmann, F, Schafhausen, P, Brümmendorf, T, Duyster, J, Blumenstengel, K, Scheid, C, Kneba, M, Kwong, Yl, Masszi, T, Petrini, M, Alimena, G, Di Raimondo, F, Rosti, G, Rotoli, B, Pane, Fabrizio, Pungolino, E, Amadori, S, Abruzzese, E, Fioritoni, G, Lauria, F, Bosi, A, Martelli, M, Rambaldi, A, Ferrara, F, Nobile, F, Gobbi, M, Carella, Am, Orlandi, Em, Leoni, P, Tiribelli, M, Levis, A, Imamura, M, Takahashi, N, Tsukamoto, N, Chiba, S, Nagai, T, Okamoto, S, Miura, O, Kurokawa, M, Ohnishi, K, Toba, K, Nakao, S, Tomita, A, Miyamura, K, Hino, M, Maeda, Y, Kimura, A, Kawaguchi, T, Miyazaki, Y, Nakaseko, C, Jinnai, I, Matsuda, A, Matsumura, I, Ishikawa, J, Ohyashiki, K, Okada, M, Usuki, K, Kobayashi, Y, Ohishi, K, Imai, K, Miyawaki, S, Kanda, Y, Park, Sy, Kim, Hj, Sohn, Sk, Lee, Kh, Jung, Cw, Ong, Tc, Gómez Almaguer, D, Kassack, J, Ossenkoppele, Gj, Gedde Dahl, T, Hjorth Hansen, H, Jedrzejczak, W, Dmoszynska, A, Starzak Dwozdz, J, Holowiecki, J, Kyrcz Krzemieñ, S, Kuliczkowski, K, Zaritsky, A, Turkina, A, Pospelova, T, Goh, Yt, Koh, Lp, Demitrovicova, L, Mistrik, M, Ruff, P, Louw, V, Dreosti, Lm, Novitzky, N, Cohen, G, Cervantes, F, Cañizo, C, de Paz, R, del Castillo, S, Perez Encinas, M, Sanz Alonso, M, Marin, F, Pérez López, R, Hernandez Boluda, J, Echeveste Gutierrez, Ma, Odriozola, J, Herrera, P, Steegman, Jl, Conde, E, Lopez, P, Giraldo, P, Boque, C, Heredia, B, Font, Aj, Rodriguez, Rf, Rodriguez, Mj, Batlle, J, Stenke, L, Lehmann, S, Wadenvik, H, Simonsson, B, Markevärn, B, Själander, A, Richter, J, Bjoreman, M, Eriksson, Km, Chalandon, Y, Shih, Ly, Yao, M, Wang, Mc, Jootar, S, Bunworasate, U, Ulkü, B, Haznedar, R, Undar, B, Sahin, B, Marin, D, Smith, G, Byrne, J, Holyoake, T, Kalaycio, M, Akard, L, Heaney, M, Al Janadi, A, Goldberg, S, Powell, B, Harker, Wg, Shea, T, Gingrich, R, Glass, J, Paquette, R, Siegrist, C, Woodson, M, Fehrenbacher, L, Koh, H, Flinn, I, Arrowsmith, E, Ervin, T, Guerra, M, Wallach, H, Berry, W, Burke, J, Edenfield, W, Guzley, G, Davis, J, Richards, D, Schlossman, D, Kolibaba, K, Alemany, C, Savin, M, Robbins, G, Lopez, J, Goldman, Jm, Camm, J, Schiffer, Ca, and Sargent, D. J.
- Published
- 2010
10. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia
- Author
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Saglio, Giuseppe, Kim, Dw, Issaragrisil, S, le Coutre, P, Etienne, G, Lobo, C, Pasquini, R, Clark, Re, Hochhaus, A, Hughes, Tp, Gallagher, N, Hoenekopp, A, Dong, M, Haque, A, Larson, Ra, and Kantarjian, Hm
- Published
- 2010
11. Twelve-month diagnosed prevalence of behavioral health disorders among elderly medicare and medicaid members.
- Author
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Lin WC, Zhang J, Leung GY, and Clark RE
- Abstract
OBJECTIVES: : We examined the 12-month diagnosed prevalence of behavioral health disorders (BHDs) and dementia among elderly Medicare and Medicaid members in Massachusetts by primary payment source group (dual eligible, Medicare only, and Medicaid only) and age group (65-74 years, 75-84 years, and 85 years and older). DESIGN: : A retrospective cross-sectional study. SETTING: : Medicare and Medicaid programs. PARTICIPANTS: : Massachusetts Medicare or Medicaid enrollees age 65 and older as of January 1, 2005, (N = 679,182). MEASUREMENTS: : International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes recorded on Medicare and Medicaid claims were used to identify the BHDs. RESULTS: : The 12-month diagnosed prevalence was 19.4% for any BHD and 11.2% for dementia. The most common BHDs by disease category were major depression (severe mental illness [SMI]), other depression (other mental illness [OMI]), and alcohol abuse or dependence (subtance use disorder [SUD]). Dual eligibles had a considerably higher diagnosed prevalence of any BHD (38.8%), compared with 16.1% in the Medicare only group. The 12-month diagnosed prevalence of SMI, OMI, and dementia was higher in the older-age groups. Co-occurring SUD was higher for younger dual eligibiles. Dementia and mental illness co-occurred at much higher rates for dual eligibles than for either of the single-insurance groups. This combination increased with age in all three groups. CONCLUSIONS: : The 12-month prevalence of BHDs and dementia among elderly dual eligibles was disproportionately higher than other elderly Medicare or Medicaid members. However, access barriers to behavioral health services for this vulnerable population could be significant because Medicare and Medicaid payment limitations resulted in financial disincentives for providing these services. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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12. Behavioral disorders and diabetes-related outcomes among Massachusetts Medicare and Medicaid beneficiaries.
- Author
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Leung G, Zhang J, Lin WC, Clark RE, Leung, Gary, Zhang, Jianying, Lin, Wen-Chieh, and Clark, Robin E
- Abstract
Objective: The study investigated whether Massachusetts beneficiaries of Medicare, Medicaid, or both programs who have behavioral disorders have higher rates of diabetes-related complications and hospitalizations.Methods: This was a retrospective study using merged Medicare and Medicaid claims data from Massachusetts in 2004 and 2005. The study included beneficiaries who had type 2 diabetes, who stayed in nursing homes for fewer than 90 days, and who were enrolled in Medicare or Medicaid (or both) for at least ten months during the study period. ICD-9-CM and Current Procedural Terminology codes were used to identify diabetes complications (eye complications, nephropathy, neuropathy, ischemic heart disease, cerebrovascular disease, lower-limb amputations, and diabetes-related hospitalizations). The rates of adverse diabetes outcomes were compared across behavioral disorders as identified by ICD-9-CM diagnoses. While adjusting for case mix, multivariate logistic regressions were performed to compare the odds of adverse diabetes outcomes among people with mental or substance use disorders with those without these disorders.Results: A total of 106,174 individuals met inclusion criteria. Results from adjusted analysis showed a mixed picture of the relationships between behavioral disorders and adverse diabetes outcomes. Although substance use disorders were associated with higher odds of lower-limb amputations and diabetes-related hospitalizations, beneficiaries with schizophrenia or paranoid states had lower odds of adverse diabetes outcomes.Conclusions: Medicaid and Medicare beneficiaries with alcohol or drug use disorders had higher rates of adverse diabetes outcomes than other groups, whereas beneficiaries with mental disorders had lower rates of diabetes-related complications. [ABSTRACT FROM AUTHOR]- Published
- 2011
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13. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy.
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Grimwade D, Jovanovic JV, Hills RK, Nugent EA, Patel Y, Flora R, Diverio D, Jones K, Aslett H, Batson E, Rennie K, Angell R, Clark RE, Solomon E, Lo-Coco F, Wheatley K, Burnett AK, Grimwade, David, Jovanovic, Jelena V, and Hills, Robert K
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- 2009
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14. Beyond health plans: behavioral health disorders and quality of diabetes and asthma care for medicaid beneficiaries.
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Clark RE, Weir S, Ouellette RA, Zhang J, and Baxter JD
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- 2009
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15. Racial/ethnic disparities in mental health treatment in six Medicaid programs.
- Author
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Samnaliev M, McGovern MP, and Clark RE
- Abstract
Little is known about ethnic and racial disparities in mental health care among Medicaid beneficiaries. The association between ethnicity and race and the utilization of mental health care was explored in six Medicaid programs. The analysis distinguished between different settings of care, including community-based, outpatient hospital, inpatient, and emergency departments (EDs). Racial and ethnic disparities in mental health care were observed across state Medicaid programs. Hispanic and African American beneficiaries with mental illness were much less likely than Whites to be treated in community-based settings. African Americans were more likely to receive mental health treatment in inpatient, ED, and outpatient hospital settings in some states. The implications of these findings and possible initiatives to enhance community-based mental health care among African American and Hispanic Medicaid beneficiaries are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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16. Patterns of health care utilization for asthma treatment in adults with substance use disorders.
- Author
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Baxter JD, Samnaliev M, and Clark RE
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- 2008
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17. Treatment for co-occurring mental and substance use disorders in five state Medicaid programs.
- Author
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Clark RE, Samnaliev M, McGovern MP, Clark, Robin E, Samnaliev, Mihail, and McGovern, Mark P
- Abstract
Objectives: This study described the locations and patterns of psychiatric and substance abuse treatment for Medicaid beneficiaries with co-occurring mental and substance use disorders in five states.Methods: Medicaid beneficiaries aged 21 to 65 with psychiatric or substance use disorders were identified with claims and encounter records. Groups were further divided into those with and those without a diagnosed substance use disorder. Adjusted odds of treatment in community-based settings, inpatient facilities, emergency departments, and hospital outpatient departments were calculated.Results: A total of 92,355 persons had a psychiatric disorder, 34,158 had a substance use disorder, and 14,256 had co-occurring psychiatric and substance use disorders. In all five states, beneficiaries with severe mental illness (schizophrenia, bipolar disorder, or major depression) and a substance use disorder had higher odds of inpatient, emergency department, and hospital-based outpatient psychiatric treatment, compared with those with severe mental illness alone. In four of five states, both severe and less severe mental illness and a co-occurring substance use disorder were associated with lower odds of community-based treatment compared with those with the respective mental illness alone. Compared with those with less severe mental illness alone, individuals with less severe psychiatric disorders and a co-occurring substance use disorder had higher odds of inpatient treatment in all states and of emergency department use in three of five states. Odds of inpatient and outpatient hospital use and emergency department use for substance abuse treatment were higher for persons with severe mental illness and a co-occurring substance use disorder in most states, compared with odds for those with a substance use disorder alone.Conclusions: Heavy inpatient and emergency department use by Medicaid beneficiaries with co-occurring substance use disorders is a consistent cross-state problem. Co-occurring disorders may decrease the likelihood of community-based treatment for those with less severe mental disorders and for those with severe mental illness, suggesting that policies focusing only on these settings may miss a significant proportion of people with these co-occurring disorders. [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
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18. Estimated payments to employment service providers for persons with mental illness in the Ticket to Work program.
- Author
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Cook JA, Leff HS, Blyler CR, Gold PB, Goldberg RW, Clark RE, Onken SJ, Shafer MS, Blankertz LE, McFarlane WR, Razzano LA, and Burke-Miller JK
- Abstract
OBJECTIVE: The Ticket to Work and Work Incentives Improvement Act of 1999 removes work disincentives and promotes access to vocational services for people with disabilities. This study calculated the amount of payments that would have been made to employment service providers if study participants had been enrolled in the Ticket program. METHODS: Data were from 450 Social Security Disability Insurance beneficiaries with psychiatric disabilities enrolled in a multisite study of supported employment. Earnings over two years were used to calculate provider payments under two reimbursement formulas used in the Ticket program. RESULTS: Only a quarter of service recipients (26 percent) reached earnings levels that would have triggered provider payments under the first reimbursement formula. Only 4 percent would have completed their trial work period and left the rolls, generating payments under the second formula. CONCLUSIONS: The current provider payment systems of the Ticket to Work program do not reflect the reality of rehabilitation for individuals with severe mental illness. Reforms should take into account outcomes of return-to-work services for this population. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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19. Cost-effectiveness of strategies that are intended to prevent kernicterus in newborn infants.
- Author
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Suresh GK and Clark RE
- Abstract
OBJECTIVE: There is concern about an increasing incidence of kernicterus in healthy term neonates in the United States. Although the incidence of kernicterus is unknown, several potential strategies that are intended to prevent kernicterus have been proposed by experts. It is necessary to assess the costs, benefits, and risks of such strategies before widespread policy changes are made. The objective of this study was to determine the direct costs to prevent a case of kernicterus with the following 3 strategies: (1) universal follow-up in the office or at home within 1 to 2 days of early newborn discharge, (2) routine predischarge serum bilirubin with selective follow-up and laboratory testing, and (3) routine predischarge transcutaneous bilirubin with selective follow-up and laboratory testing. METHODS: We performed an incremental cost-effectiveness analysis of the 3 strategies compared with current practice. We used a decision analytic model and a spreadsheet to estimate the direct costs and outcomes, including the savings resulting from prevented kernicterus, for an annual cohort of 2,800000 healthy term newborns who are eligible for early discharge. We used a modified societal perspective and 2002 US dollars. With each strategy, the test and treatment thresholds for hyperbilirubinemia are lowered compared with current practice. RESULTS: With the base-case assumptions (current incidence of kernicterus 1:100 000 and a relative risk reduction [RRR] of 0.7 with each strategy), the cost to prevent 1 case of kernicterus was 10,321463 dollars, 5,743905 dollars, and 9,191352 dollars respectively for strategies 1, 2, and 3 listed above. The total annual incremental costs for the cohort were, respectively, 202,300671 dollars, 112,580535 dollars, and 180,150494 dollars. Sensitivity analyses showed that the cost per case is highly dependent on the population incidence of kernicterus and the RRR with each strategy, both of which are currently unknown. In our model, annual cost savings of 46,179465 dollars for the cohort would result with strategy 2, if the incidence of kernicterus is high (1:10,000 births or higher) and the RRR is high (> or =0.7). If the incidence is lower or the RRR is lower, then the cost per case prevented ranged from 4,145676 dollars to as high as 77,650240 dollars. CONCLUSIONS: Widespread implementation of these strategies is likely to increase health care costs significantly with uncertain benefits. It is premature to implement routine predischarge serum or transcutaneous bilirubin screening on a large scale. However, universal follow-up may have benefits beyond kernicterus prevention, which we did not include in our model. Research is required to determine the epidemiology, risk factors, and causes of kernicterus; to evaluate the effectiveness of strategies intended to prevent kernicterus; and to determine the cost per quality-adjusted life year with any proposed preventive strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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20. Employment and security (Response to 'The economic advancement of the mentally ill in the community: 2. Economic choices and disincentives' by R. Warner and P. Polak)
- Author
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Clark RE
- Published
- 1995
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21. Creating work opportunities for people with severe mental illness (response to 'The economic advancement of the mentally ill in the community'.
- Author
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Clark RE
- Published
- 1995
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22. Expenditures of time and money by families of people with severe mental illness and substance use disorders.
- Author
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Clark RE and Drakie RRE
- Abstract
Families are typically a major source of support for people with mental illness, but substance abuse places an additional burden on family relations and could reduce the amount of direct support they give. Data from families of 169 people with co-occurring mental illness and substance abuse indicate that they give a substantial amount of time and money to their relatives with dual disorders. More severe current substance abuse appeared to reduce family spending but not direct caregiving. Clients with more severe alcohol problems were more likely to live with parents than with other family members. [ABSTRACT FROM AUTHOR]
- Published
- 1994
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23. Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin.
- Author
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Krunic, AL, Garrod, DR, Madani, S, Buchanan, MD, Clark, RE, Krunic, A L, Garrod, D R, Buchanan, M D, and Clark, R E
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- 1998
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24. Legal costs for the dually diagnosed points to need for more SA treatment
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Clark, RE, Ricketts, SK, and MCHugo, GJ
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Costs (Law) -- Demographic aspects ,Mental illness -- Care and treatment ,Substance abuse -- Care and treatment ,Health ,Psychology and mental health ,Care and treatment ,Demographic aspects - Abstract
Researchers with the New Hampshire-Dartmouth Psychiatric Research Center and the Dartmouth Medical School set out to determine legal involvement and costs for people with co-occurring severe mental illness and substance [...]
- Published
- 1999
25. Initial reduction of therapy improves the chance of successful complete treatment discontinuation in chronic myeloid leukaemia: Final results of the British DESTINY Study
- Author
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Clark, RE and Clark RE, Polydoros F, Apperley JF, Milojkovic D, Rothwell K, Po
26. Laparoscopically assisted splenectomy for idiopathic thrombocytopenic purpura in a previously conserved spleen.
- Author
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Isherwood P, Hershman MJ, Hartley M, and Clark RE
- Published
- 2001
27. A predominance of R5-like HIV genotypes in vaginal secretions is associated with elevated plasma HIV-1 RNA levels and the absence of anti-retroviral therapy
- Author
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Lacour Nedra, Clark Rebecca A, Kissinger Patricia J, Randolph Tara C, and Amedee Angela M
- Subjects
Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract HIV expressed in genital secretions provides the inoculum from which transmitting variants are selected, both in sexual transmission and mother-to-infant transmission during partuition. Characterization of HIV levels and genotypes found in vaginal secretions and the impact of anti-retroviral therapy (ART) on this virus can provide valuable insight for the prevention of HIV transmission. Vaginal HIV was evaluated in a cohort of 43 women attending a New Orleans HIV outpatient clinic. Predominant vaginal genotypes were characterized as R5- or X4-like by heteroduplex tracking analyses of the envelope V3 region. Most women (67.4%) shed R5-like genotypes in vaginal secretions which was associated with elevated plasma HIV levels (≥ 10,000 copies HIV-RNA/mL) and absence of ART. Because R5-like genotypes are more frequently associated with transmission, these observations suggest that the majority of women shedding HIV in genital secretions present a transmission risk. The levels of vaginal virus were similar between both groups, but shedding of X4-like genotypes was associated with lower plasma viral loads and the use of ART, suggesting that ART use may impact the genotypes of virus found in the female genital compartment.
- Published
- 2008
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28. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013
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Timothy P. Hughes, Martin C. Müller, Michael W. Deininger, Philippe Rousselot, Richard A. Larson, Michele Baccarani, Richard E. Clark, Fabrizio Pane, Andreas Hochhaus, Richard T. Silver, Henrik Hjorth-Hansen, Giuseppe Saglio, Jiri Mayer, Giovanni Martinelli, Jeffrey H. Lipton, Charles A. Schiffer, Dietger Niederwieser, Jerald P. Radich, Jane F. Apperley, Susanne Saußele, Gianantonio Rosti, Bengt Simonsson, François Guilhot, Francisco Cervantes, Simona Soverini, John M. Goldman, François Xavier Mahon, Juan Luis Steegmann, Rüdiger Hehlmann, Dong-Wook Kim, Hagop M. Kantarjian, Jorge E. Cortes, Baccarani, M, Deininger, Mw, Rosti, G, Hochhaus, A, Soverini, S, Apperley, Jf, Cervantes, F, Clark, Re, Cortes, Je, Guilhot, F, Hjorth Hansen, H, Hughes, Tp, Kantarjian, Hm, Kim, Dw, Larson, Ra, Lipton, Jh, Mahon, Fx, Martinelli, G, Mayer, J, M?ller, Mc, Niederwieser, D, Pane, Fabrizio, Radich, Jp, Rousselot, P, Saglio, G, Sau?ele, S, Schiffer, C, Silver, R, Simonsson, B, Steegmann, Jl, Goldman, Jm, Hehlmann, R., Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Müller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saußele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R., University of Bologna, University of Utah, and Université de Poitiers
- Subjects
polymerase chain reaction ,Fusion Proteins, bcr-abl ,Review Article ,protein-tyrosine kinase inhibitor ,Biochemistry ,Piperazines ,cytogenetics ,chemistry.chemical_compound ,European LeukemiaNet ,0302 clinical medicine ,imatinib mesylate ,hemic and lymphatic diseases ,dasatinib ,BCR-ABL ,Randomized Controlled Trials as Topic ,0303 health sciences ,withdrawing treatment ,Ponatinib ,leukemia ,Myeloid leukemia ,Hematology ,Prognosis ,3. Good health ,Europe ,chronic ,Dasatinib ,Treatment Outcome ,030220 oncology & carcinogenesis ,Benzamides ,medicine.drug ,medicine.medical_specialty ,myelocytic ,Immunology ,Antineoplastic Agents ,second line treatment ,03 medical and health sciences ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,TYROSINE KINASE INHIBITORS ,Humans ,nilotinib ,030304 developmental biology ,allogeneic stem cell transplant ,business.industry ,Cell Biology ,Discontinuation ,Transplantation ,Thiazoles ,Pyrimidines ,Imatinib mesylate ,Nilotinib ,chemistry ,business ,CHRONIC MYELOID LEUKEMIA (CML) ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Stem Cell Transplantation ,transplantation - Abstract
Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, 10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome–positive [Ph+] >95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
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- 2013
29. Multidisciplinary Velopharyngeal Dysfunction Evaluation Helps Detect Non-classic Cases of 22q11.2 Deletion.
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Stanek K, Wang AT, Hseu AF, Clark RE, Meara JG, Nuss RC, Ganske IM, and Rogers-Vizena CR
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Objective: To explore the role of multidisciplinary velopharyngeal dysfunction (VPD) assessment in diagnosing 22q11.2 deletion syndrome (22q) in children., Design: Retrospective cohort study., Setting: Multidisciplinary VPD clinic at a tertiary pediatric hospital., Patients, Participants: Seventy-five children with genetically confirmed 22q evaluated at the VPD clinic between February 2007 and February 2023, including both previously diagnosed patients and those newly diagnosed as a result of VPD evaluation., Interventions: Comprehensive review of medical records, utilizing ICD-10 codes and an institutional tool for keyword searches, to identify patients and collect data on clinical variables and outcomes., Main Outcome Measures: Characteristics of children with 22q, pathways to diagnosis, and clinical presentations that led to genetic testing for 22q., Results: Of the 75 children, 9 were newly diagnosed with 22q following VPD evaluation. Non-cleft VPI was a significant indicator for 22q in children not previously diagnosed, occurring in 100% of newly diagnosed cases compared to 52% of cases with existing 22q diagnosis ( P = .008). Additional clinical findings leading to diagnosis included congenital heart disease, craniofacial abnormalities, and developmental delays., Conclusions: VPD evaluations, particularly the presence of non-cleft VPI, play a crucial role in identifying undiagnosed cases of 22q. This underscores the need for clinicians, including plastic surgeons, otolaryngologists, and speech-language pathologists, to maintain a high degree of suspicion for 22q in children presenting with VPI without a clear etiology. Multidisciplinary approaches are essential for early diagnosis and management of this complex condition., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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30. Comparative Study of Pharyngeal Flap Outcomes between Children with 22q11.2 Deletion Syndrome and Nonsyndromic Cleft Lip and Palate.
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Wang AT, Hseu AF, Staffa SJ, Clark RE, Meara JG, Nuss RC, Ganske IM, and Rogers-Vizena CR
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- Humans, Male, Female, Retrospective Studies, Child, Treatment Outcome, Child, Preschool, Plastic Surgery Procedures methods, Plastic Surgery Procedures adverse effects, Postoperative Complications etiology, Postoperative Complications epidemiology, Adolescent, Velopharyngeal Insufficiency surgery, Velopharyngeal Insufficiency etiology, Cleft Palate surgery, Cleft Palate complications, Surgical Flaps transplantation, DiGeorge Syndrome surgery, DiGeorge Syndrome complications, Cleft Lip surgery, Pharynx surgery
- Abstract
Background: Management of velopharyngeal insufficiency (VPI) in 22q11.2 deletion syndrome is challenging. The authors compared pharyngeal flap outcomes in children with 22q11.2 deletion syndrome to those with nonsyndromic cleft lip and palate (CLP) to assess risk of poor speech outcomes and negative sequelae., Methods: Children with 22q11.2 deletion syndrome or CLP treated with pharyngeal flap through a multidisciplinary VPI clinic between 2009 and 2020 were retrospectively reviewed. Preoperative and postoperative speech assessments, perioperative characteristics, and complications were identified., Results: Thirty-six children with 22q11.2 deletion syndrome and 40 with CLP were included. Age at surgery ( P = 0.121), preoperative velopharyngeal competence score ( P = 0.702), and preoperative resonance ( P = 0.999) were similar between groups. Pharyngeal flaps were wider ( P = 0.038) and length of stay longer in the 22q11.2 deletion syndrome group ( P = 0.031). On short-term follow-up 4 months after surgery, similar speech outcomes were seen between groups. At long-term follow-up greater than 12 months after surgery, 86.7% of 22q11.2 deletion syndrome versus 100% of CLP ( P = 0.122) children had improvement in velopharyngeal function; however, fewer children with 22q11.2 deletion syndrome (60.0%) achieved a completely "competent" velopharyngeal competence score compared with those with CLP (92.6%) ( P = 0.016). Nasal regurgitation improved for both groups, with a greater improvement in those with 22q11.2 deletion syndrome ( P = 0.026). Revision rate ( P = 0.609) and new-onset obstructive sleep apnea ( P = 0.999) were similar between groups., Conclusions: Children with 22q11.2 deletion syndrome have improved speech after pharyngeal flap, but they may be less likely to reach normal velopharyngeal function over the long term than those with CLP; however, negative sequelae do not differ. Improvement in nasal regurgitation is a uniquely positive outcome in this population., Clinical Question/level of Evidence: Risk, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)
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- 2024
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31. Tracking flight activity of potato leafhopper (Hemiptera: Cicadellidae) with the Midwest Suction Trap Network.
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Lagos-Kutz DM, Clark RE, Seiter N, Clough SJ, Hartman GL, and Crossley MS
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- Animals, Insect Control, Flight, Animal, Hemiptera physiology, Seasons
- Abstract
Potato leafhopper (PLH), Empoasca fabae Harris (Hemiptera: Cicadellidae), is an economic pest of a variety of crops that migrates between overwintering sites in the southern United States and northern breeding grounds. Since 2005, the Midwest Suction Trap Network (STN) has monitored the magnitude and timing of aerially dispersing aphids' activity, but the potential of the network to monitor other taxa is only beginning to be explored. Here, we use the Midwest STN to examine how the magnitude and timing of PLH activity vary with weather, cropland cover, and time of year. We found that weekly PLH activity increased early in the season (May-June) with increasing degree day accumulation and decreased mid-season (July-August) with increasing occurrence of rain. The first detections occurred earlier in southern latitudes, while the last detections occurred sooner, when there was more surrounding potato land cover, and later over time between 2018 and 2021 and in southern latitudes. PLH activity was thus longer in duration in southern latitudes and has continued to extend later into the year overall. Resolving uncertainty about how well the Midwest STN captures migratory activity and how closely suction trap detections reflect local population densities in crop fields remain important research priorities before the potential of the Midwest STN for PLH monitoring can be realized. Still, observed patterns suggest that PLH could increase in economic importance as insects disperse over larger portions of the growing season in the warming, agriculturally productive US Midwest and that the STN can become a useful tool to monitor these changes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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32. Sigmoid volvulus in pregnancy: A rare case report.
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Pfeiffer AF, Clark RE, Sullivan J, Rizvi SAA, Byrne JJ, and Boyd AR
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- Female, Humans, Pregnancy, Intestinal Volvulus diagnostic imaging, Intestinal Volvulus surgery, Pregnancy Complications diagnosis, Sigmoid Diseases
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- 2024
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33. Response: Sigmoid volvulus in pregnancy: A rare case report.
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Pfeiffer AF, Clark RE, Sullivan J, Rizvi SAA, Byrne JJ, and Boyd AR
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- Female, Humans, Pregnancy, Case Reports as Topic, Intestinal Volvulus surgery, Intestinal Volvulus diagnostic imaging, Pregnancy Complications, Sigmoid Diseases
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- 2024
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34. Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.
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Metz VE, Ray GT, Palzes V, Binswanger I, Altschuler A, Karmali RN, Ahmedani BK, Andrade SE, Boscarino JA, Clark RE, Haller IV, Hechter RC, Roblin DW, Sanchez K, Bailey SR, McCarty D, Stephens KA, Rosa CL, Rubinstein AL, and Campbell CI
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- Humans, Male, Female, Middle Aged, United States epidemiology, Adult, Cohort Studies, Aged, Emergency Service, Hospital statistics & numerical data, Benzodiazepines adverse effects, Benzodiazepines administration & dosage, Drug Tapering, Young Adult, Opiate Overdose epidemiology, Opiate Overdose mortality, Analgesics, Opioid adverse effects, Analgesics, Opioid administration & dosage
- Abstract
Background: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events., Objective: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality)., Design: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of ≥ 50 during six consecutive months., Patients: We identified 60,040 non-cancer patients with ≥ one 2-month dose reduction period (600,234 unique dose reduction periods)., Main Measures: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics., Key Results: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality., Conclusions: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)
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- 2024
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35. Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.
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Nguyen AP, Palzes VA, Binswanger IA, Ahmedani BK, Altschuler A, Andrade SE, Bailey SR, Clark RE, Haller IV, Hechter RC, Karmali R, Metz VE, Poulsen MN, Roblin DW, Rosa CL, Rubinstein AL, Sanchez K, Stephens KA, Yarborough BJH, and Campbell CI
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- Adult, Humans, Analgesics, Opioid therapeutic use, Retrospective Studies, Outpatients, Prescriptions, Headache, Practice Patterns, Physicians', Back Pain, Musculoskeletal Pain diagnosis, Musculoskeletal Pain drug therapy, Radiculopathy
- Abstract
Objective: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription., Methods: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription., Results: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply)., Conclusions: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: together to conduct postmarketing studies required by the Food and Drug Administration that assess risks related to opioid analgesic use. Dr. Andrade has received research support on grants to the University of Massachusetts Chan Medical School from Pfizer, Inc., GlaxoSmithKline, and the Reagan-Udall Foundation, and consulting fees from Corevitas LLC. Dr. Binswanger receives royalties for educational content on the health of incarcerated persons from UpToDate. Ms. Rosa was substantially involved in the study, consistent with her role as Scientific Officer. She had no substantial involvement in the other cited grants., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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36. Cardiovascular risk in chronic myeloid leukaemia: A multidisciplinary consensus on screening and management.
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Milojkovic D, Lyon AR, Mehta P, Dimitriadou E, Choudhuri S, Manisty C, Cheshire N, Crozier K, Basker N, Amer K, Purcell S, Tan S, and Clark RE
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- Humans, Protein Kinase Inhibitors adverse effects, Consensus, Risk Factors, Heart Disease Risk Factors, Antineoplastic Agents therapeutic use, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Abstract
Introduction: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for chronic myeloid leukaemia (CML), but cardiovascular (CV) risk and exacerbation of underlying risk factors associated with TKIs have become widely debated. Real-world evidence reveals little application of CV risk factor screening or continued monitoring within UK CML management. This consensus paper presents practical recommendations to assist healthcare professionals in conducting CV screening/comorbidity management for patients receiving TKIs., Methods: We conducted a multidisciplinary panel meeting and two iterative surveys involving 10 CML specialists: five haematologists, two cardio-oncologists, one vascular surgeon, one haemato-oncology pharmacist and one specialist nurse practitioner., Results: The panel recommended that patients commencing second-/third-generation TKIs undergo formal CV risk assessment at baseline, with additional investigations and involvement of cardiologists/vascular surgeons for those with high CV risk. During treatment, patients should undergo CV monitoring, with the nature and frequency of testing dependent on TKI and baseline CV risk. For patients who develop CV adverse events, decision-making around TKI interruption, cessation or change should be multidisciplinary and balance CV and haematological risk., Conclusion: The panel anticipates these recommendations will support healthcare professionals in implementing CV risk screening and monitoring, broadly and consistently, and thereby help optimise TKI treatment for CML., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)
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- 2023
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37. Temporal and spatial dynamics of the emerald ash borer invasion in Connecticut as shown by the native digging wasp Cerceris fumipennis (Hymenoptera: Crabronidae ).
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Rutledge CE and Clark RE
- Abstract
Detecting and monitoring populations of the invasive emerald ash borer (EAB) is crucial to successful management of the pest and evaluation of its ecological impacts. However, the beetle's cryptic habit makes accurate monitoring costly and time-consuming. Biosurveillance takes advantage of the foraging effort of a predatory wasp Cerceris fumipennis (Hymenoptera: Crabronidae). This native, solitary, ground-nesting hunting wasp hunts adult buprestid beetles to provision its brood cells. By intercepting the hunting wasps, we can learn which species of buprestids are in the surrounding forest. The resulting data provides information on the presence and relative abundance of invasive buprestids like EAB which can supplement other monitoring efforts. In this paper we share results of ten years of biosurveillance surveys of the EAB in Connecticut. Among 112 sites, we observed EAB populations; from first detection, through the population peak and then through to the population crash, matching patterns observed in other regions of the United States. We also observed the spread of the EAB relative abundance as it moved through the state following an invasion front starting in New Haven, Co. The average time from first detection to population crash was nine years. On average, populations peaked three years after first detection, and remained at peak levels for three to four years. Population decline was gradual and took another three to four years. Notably, no evidence of a second introduction to Connecticut was seen with proportional abundance increasing over time after expanding outward from the introduction point. These results corroborate other traditional monitoring efforts in the eastern U.S. and provide independent validation of predicted population dynamics in ash stands., Competing Interests: Author RC was employed by company EcoData Technology. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rutledge and Clark.)
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- 2023
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38. Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation.
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Karg E, Baldow C, Zerjatke T, Clark RE, Roeder I, Fassoni AC, and Glauche I
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Introduction: Discontinuation of tyrosine kinase inhibitor (TKI) treatment is emerging as the main therapy goal for Chronic Myeloid Leukemia (CML) patients. The DESTINY trial showed that TKI dose reduction prior to cessation can lead to an increased number of patients achieving sustained treatment free remission (TFR). However, there has been no systematic investigation to evaluate how dose reduction regimens can further improve the success of TKI stop trials., Methods: Here, we apply an established mathematical model of CML therapy to investigate different TKI dose reduction schemes prior to therapy cessation and evaluate them with respect to the total amount of drug used and the expected TFR success., Results: Our systematic analysis confirms clinical findings that the overall time of TKI treatment is a major determinant of TFR success, while highlighting that lower dose TKI treatment for the same duration is equally sufficient for many patients. Our results further suggest that a stepwise dose reduction prior to TKI cessation can increase the success rate of TFR, while substantially reducing the amount of administered TKI., Discussion: Our findings illustrate the potential of dose reduction schemes prior to treatment cessation and suggest corresponding and clinically testable strategies that are applicable to many CML patients., Competing Interests: RC is a consultant for Pfizer. IR reports receiving a commercial research grant from Bristol-Myers Squibb and has received speakers bureau honoraria from Bristol-Myers Squibb and Janssen-Cilag. IG reports receiving a commercial research grant from Bristol-Myers Squibb and from GlaxoSmithKline. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Karg, Baldow, Zerjatke, Clark, Roeder, Fassoni and Glauche.)
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- 2022
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39. Understanding volunteer retention in a complex, community-centred intervention: A mixed methods study in Ontario, Canada.
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Gaber J, Clark RE, Lamarche L, Datta J, Talat S, Bomze S, Marentette-Brown S, Parascandalo F, Di Pelino S, Oliver D, Price D, Geoffrion L, and Mangin D
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- Humans, Male, Aged, Ontario, Case-Control Studies, Volunteers psychology, Quality of Life, Motivation
- Abstract
Volunteers are critical to supporting health care systems worldwide. For organisations that rely on volunteers, service to clients can be disrupted when volunteers leave their roles. Volunteer retention is a multi-layered phenomenon. In this mixed methods case-control study, we compared two naturally-occurring volunteer groups supporting a complex primary care-based programme for older adults in the community: volunteers retained by the programme, and volunteers that left. Our objectives were to describe differences between the groups and also understand how compassion changed over time for those that stayed. We collected quantitative data on demographics, the UCLA Geriatric Attitudes Scale, the Professional Quality of Life Index, the Basic Empathy Scale, the Reasons for Volunteering subscale of the Volunteerism Questionnaire and the 5-level EQ-5D. Qualitative data were collected through focus groups/interviews. Overall, 78 volunteers completed surveys and 23 participated in focus groups/interviews. Volunteers that stayed were more likely to be a little older and were a slightly higher proportion male than those who left. They also had significantly less positive attitudes towards older adults, descriptively lower Cognitive Empathy and descriptively higher Secondary Traumatic Stress. Compared to volunteers who left, volunteers retained were more likely to have said they were volunteering for Enhancement or Social purposes; however, these differences were non-significant. Over time, Compassion Satisfaction decreased with a medium effect size for those that stayed, and Burnout decreased with a small effect size. Volunteers that stayed described more logistical and client-related aspects of the programme were working well. We recommend that volunteer programmes communicate positive programme impacts that could enhance volunteers' development, communicate any client impacts to volunteers to reinforce volunteers' purposes for volunteering (thus reinforcing that their work is meaningful), and ensure logistical aspects of volunteer role work well., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)
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- 2022
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40. A randomised comparison of FLAG-Ida versus daunorubicin combined with clofarabine in relapsed or refractory acute myeloid leukaemia: Results from the UK NCRI AML17 trial.
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Russell NH, Hills RK, Kjeldsen L, Clark RE, Ali S, Cahalin P, Thomas IF, and Burnett AK
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- Chronic Disease, Cytarabine therapeutic use, Daunorubicin therapeutic use, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, United Kingdom, Vidarabine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Clofarabine therapeutic use, Idarubicin therapeutic use, Leukemia, Myeloid, Acute drug therapy
- Abstract
The prognosis for younger patients with relapsed acute myeloid leukaemia (AML) is generally dismal. Allogeneic stem cell transplantation is the preferred therapy for these patients. As part of the UK NCRI AML17 trial, daunorubicin/clofarabine (DClo) was compared with fludarabine, cytarabine, granulocyte colony-stimulating factor with idarubicin (FLAG-Ida) in 311 patients designated high-risk following course one of induction therapy, which has previously been reported. We now report the results of the same randomisation in patients who were refractory to two induction courses or subsequently relapsed. A total of 94 relapsed or refractory AML patients, usually less than 60 years of age and with mainly favourable or intermediate-risk cytogenetics, were randomised to receive up to three courses of DClo or FLAG-Ida, with the aim of proceeding to transplant. Complete remission was achieved in 74% of patients with no difference between the arms. Overall, 57% of patients received a transplant with no difference between the arms, likewise overall survival at five years showed no significant difference (21% for DClo vs. 22% for FLAG-Ida). No patient who did not receive a transplant survived beyond 21months. A stratified analysis including the 311 post course 1 high-risk patients who underwent the same randomisation showed a consistent treatment benefit for FLAG-Ida., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2022
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41. Quality of Nursing Homes Admitting Working-Age Adults With Serious Mental Illness.
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Hugunin J, Chen Q, Baek J, Clark RE, Lapane KL, and Ulbricht CM
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- Adult, Cross-Sectional Studies, Humans, Middle Aged, Nursing Homes, Patient Admission, United States, Young Adult, Psychotic Disorders, Schizophrenia epidemiology, Schizophrenia therapy
- Abstract
Objective: This cross-sectional study examined the association between nursing home quality and admission of working-age persons (ages 22-64 years) with serious mental illness., Methods: The study used 2015 national Minimum Data Set 3.0 and Nursing Home Compare (NHC) data. A logistic mixed-effects model estimated the likelihood (adjusted odds ratios [AORs] and 95% confidence intervals [CIs]) of a working-age nursing home resident having serious mental illness, by NHC health inspection quality rating. The variance partition coefficient (VPC) was calculated to quantify the variation in serious mental illness attributable to nursing home characteristics. Measures included serious mental illness (i.e., schizophrenia, bipolar disorder, and other psychotic disorders), health inspection quality rating (ranging from one star, below average, to five stars, above average), and other sociodemographic and clinical covariates., Results: Of the 343,783 working-age adults newly admitted to a nursing home in 2015 (N=14,307 facilities), 15.5% had active serious mental illness. The odds of a working-age resident having serious mental illness was lowest among nursing homes of above-average quality, compared with nursing homes of below-average quality (five-star vs. one-star facility, AOR=0.78, 95% CI=0.73-0.84). The calculated VPC from the full model was 0.11., Conclusions: These findings indicate an association between below-average nursing homes and admission of working-age persons with serious mental illness, suggesting that persons with serious mental illness may experience inequitable access to nursing homes of above-average quality. Access to alternatives to care, integration of mental health services in the community, and improving mental health care in nursing homes may help address this disparity.
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- 2022
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42. Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukemia: results of the NCRI acute myeloid leukemia 16 trial.
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Russell NH, Hills RK, Thomas A, Thomas I, Kjeldsen L, Dennis M, Craddock C, Freeman S, Clark RE, and Burnett AK
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- Adult, Aged, Female, Humans, Male, Middle Aged, Retrospective Studies, Survival Analysis, Transplantation Conditioning methods, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
Reduced intensity conditioning (RIC) transplantation is increasingly offered to older patients with acute myeloblastic leukemia. We have previously shown that a RIC allograft, particularly from a sibling donor, is beneficial in intermediate-risk patients aged 35-65 years. We here present analyses from the NCRI AML16 trial extending this experience to older patients aged 60-70 inclusive lacking favorable-risk cytogenetics. Nine hundred thirty-two patients were studied, with RIC transplant in first remission given to 144 (sibling n=52, matched unrelated donor n=92) with a median follow-up for survival from complete remission of 60 months. Comparisons of outcomes of patients transplanted versus those not were carried out using Mantel-Byar analysis. Among the 144 allografted patients, 93 had intermediate-risk cytogenetics, 18 had adverse risk and cytogenetic risk group was unknown for 33. In transplanted patients survival was 37% at 5 years, and while the survival for recipients of grafts from siblings (44%) was better than that for recipients of grafts from matched unrelated donors (34%), this difference was not statistically significant (P=0.2). When comparing RIC versus chemotherapy, survival of patients treated with the former was significantly improved (37% versus 20%, hazard ratio = 0.67 [0.53-0.84]; P<0.001). When stratified by Wheatley risk group into good, standard and poor risk there was consistent benefit for RIC across risk groups. When stratified by minimal residual disease status after course 1, there was consistent benefit for allografting. The benefit for RIC was seen in patients with a FLT3 ITD or NPM1 mutation with no evidence of a differential effect by genotype. We conclude that RIC transplantation is an attractive option for older patients with acute myeloblastic leukemia lacking favorable-risk cytogenetics and, in this study, we could not find a group that did not benefit.
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- 2022
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43. Characteristics of Working-Age Adults With Schizophrenia Newly Admitted to Nursing Homes.
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Hugunin J, Yuan Y, Baek J, Clark RE, Rothschild AJ, Lapane KL, and Ulbricht CM
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- Adult, Cross-Sectional Studies, Humans, Long-Term Care, Middle Aged, Nursing Homes, Patient Discharge, Young Adult, Schizophrenia therapy
- Abstract
Objectives: Persons aged <65 years account for a considerable proportion of US nursing home residents with schizophrenia. Because they are often excluded from psychiatric and long-term care studies, a contemporary understanding of the characteristics and management of working-age adults (22-64 years old) with schizophrenia living in nursing homes is lacking. This study describes characteristics of working-age adults with schizophrenia admitted to US nursing homes in 2015 and examines variations in these characteristics by age and admission location. Factors associated with length of stay and discharge destination were also explored., Design: This is a cross-sectional study using the Minimum Data Set 3.0 merged to Nursing Home Compare., Setting and Participants: This study examines working-age (22-64 years) adults with schizophrenia at admission to a nursing home., Methods: Descriptive statistics of resident characteristics (sociodemographic, clinical comorbidities, functional status, and treatments) and facility characteristics (ownership, geography, size, and star ratings) were examined overall, stratified by age and by admission location. Generalized estimating equation models were used to explore the associations of age, discharge to the community, and length of stay with relevant resident and facility characteristics. Coefficient estimates, adjusted odds ratios, and 95% CIs are presented., Results: Overall, many of the 28,330 working-age adults with schizophrenia had hypertension, diabetes, and obesity. Those in older age subcategories tended to have physical functional dependencies, cognitive impairments, and clinical comorbidities. Those in younger age subcategories tended to exhibit higher risk of psychiatric symptoms., Conclusions and Implications: Nursing home admission is likely inappropriate for many nursing home residents with schizophrenia aged <65 years, especially those in younger age categories. Future psychiatric and long-term care research should include these residents to better understand the role of nursing homes in their care and should explore facility-level characteristics that may impact quality of care., (Copyright © 2021. Published by Elsevier Inc.)
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- 2022
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44. A way forward for design and analysis of neuroimaging studies of memory consolidation.
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Tallman CW, Clark RE, and Smith CN
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- Humans, Neuroimaging, Magnetic Resonance Imaging methods, Hippocampus diagnostic imaging, Hippocampus physiology, Memory Consolidation physiology
- Abstract
Several novel ideas and suggestions were made in response to our discussion paper (Tallman et al., this issue). Careful consideration of the content and context of memory while accounting for the neuroanatomy and functional specialization of the hippocampus may reveal more consistent patterns in fMRI studies of memory consolidation. Below we address these ideas as well as issues that arise when interpreting the fMRI signal in memory consolidation studies. In addition, we describe new analyses suggested by the commentators that clarify our findings with respect to current theories.
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- 2022
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45. Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial.
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Brümmendorf TH, Cortes JE, Milojkovic D, Gambacorti-Passerini C, Clark RE, le Coutre P, Garcia-Gutierrez V, Chuah C, Kota V, Lipton JH, Rousselot P, Mauro MJ, Hochhaus A, Hurtado Monroy R, Leip E, Purcell S, Yver A, Viqueira A, and Deininger MW
- Subjects
- Aniline Compounds adverse effects, Humans, Imatinib Mesylate adverse effects, Nitriles, Protein Kinase Inhibitors adverse effects, Treatment Outcome, Antineoplastic Agents adverse effects, Leukemia, Myeloid, Chronic-Phase drug therapy, Quinolines adverse effects
- Abstract
This analysis from the multicenter, open-label, phase 3 BFORE trial reports efficacy and safety of bosutinib in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) after five years' follow-up. Patients were randomized to 400-mg once-daily bosutinib (n = 268) or imatinib (n = 268; three untreated). At study completion, 59.7% of bosutinib- and 58.1% of imatinib-treated patients remained on study treatment. Median duration of treatment and time on study was 55 months in both groups. Cumulative major molecular response (MMR) rate by 5 years was higher with bosutinib versus imatinib (73.9% vs. 64.6%; odds ratio, 1.57 [95% CI, 1.08-2.28]), as were cumulative MR
4 (58.2% vs. 48.1%; 1.50 [1.07-2.12]) and MR4.5 (47.4% vs. 36.6%; 1.57 [1.11-2.22]) rates. Superior MR with bosutinib versus imatinib was consistent across Sokal risk groups, with greatest benefit seen in patients with high risk. Treatment-emergent adverse events (TEAEs) were consistent with 12-month data. After 5 years of follow-up there was an increase in the incidence of cardiac, effusion, renal, and vascular TEAEs in bosutinib- and imatinib-treated patients, but overall, no new safety signals were identified. These final results support 400-mg once-daily bosutinib as standard-of-care in patients with newly diagnosed CP CML.This trial was registered at www.clinicaltrials.gov as #NCT02130557., (© 2022. The Author(s).)- Published
- 2022
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46. Human brain activity and functional connectivity as memories age from one hour to one month.
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Tallman CW, Clark RE, and Smith CN
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- Animals, Humans, Magnetic Resonance Imaging, Hippocampus diagnostic imaging, Hippocampus physiology, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex physiology, Brain Mapping, Brain diagnostic imaging, Brain physiology, Memory Consolidation
- Abstract
Theories of memory consolidation suggest the role of brain regions and connectivity between brain regions change as memories age. Human lesion studies indicate memories become hippocampus-independent over years, whereas animal studies suggest this process occurs across relatively short intervals, from days to weeks. Human neuroimaging studies suggest that changes in hippocampal and cortical activity and connectivity can be detected over these short intervals, but many of these studies examined only two time periods. We examined memory and fMRI activity for photos of indoor and outdoor scenes across four time periods to examine these neural changes more carefully. Participants (N = 21) studied scenes 1 hour, 1 day, 1 week, or 1 month before scanning. During scanning, participants viewed scenes, made old/new recognition memory judgments, and gave confidence ratings. Memory accuracy, confidence ratings, and response times changed with memory age. Brain activity in a widespread cortical network either increased or decreased with memory age, whereas hippocampal activity was not related to memory age. These findings were almost identical when effects of behavioral changes across time periods were minimized. Functional connectivity of the ventromedial prefrontal cortex with the posterior parietal cortex increased with memory age. By contrast, functional connectivity of the hippocampus with the parahippocampal cortex and fusiform gyrus decreased with memory age. In sum, we detected changes in cortical activity and changes in hippocampal and cortical connectivity with memory age across short intervals. These findings provide support for the predictions of systems consolidation and suggest that these changes begin soon after memories are formed.
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- 2022
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47. A retrospective observational research study to describe the real-world use of bosutinib in patients with chronic myeloid leukemia in the United Kingdom and the Netherlands.
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Claudiani S, Janssen JJWM, Byrne J, Smith G, Blijlevens N, Raghavan M, Smith M, Clark RE, Mclain-Smith S, Carter AM, Milojkovic D, and Apperley JF
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- Aniline Compounds, Humans, Netherlands epidemiology, Nitriles, Protein Kinase Inhibitors adverse effects, Retrospective Studies, Antineoplastic Agents adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Quinolines adverse effects
- Abstract
Objectives: To describe the real-world effectiveness and safety of bosutinib in patients with chronic myeloid leukemia (CML)., Methods: This was a multi-center, retrospective, non-interventional chart review study conducted in 10 hospitals in the United Kingdom and the Netherlands., Results: Eighty-seven patients were included. Bosutinib was the third-line tyrosine kinase inhibitor (TKI) in 33 (38%) and fourth-line in 44 (51%) patients. Median treatment duration was 15.6 months. Among 84 patients in chronic phase (CP) at baseline, 26 (31%) switched to bosutinib due to resistance and 57 (68%) due to intolerance to prior TKIs. Cumulative complete cytogenetic and major molecular response rates in CP patients were 67% and 55%, respectively. After a median follow-up of 21.5 months, nine (11%) patients in CP died; estimated overall survival rates at 1 and 2 years postbosutinib initiation were 95% and 91%, respectively. Overall, 33/87 (38%) patients discontinued bosutinib due to either lack of efficacy/disease progression (17%), adverse events (14%), death (2%), or other reasons (5%). Eighty-two (94%) patients experienced ≥1 adverse event possibly related to bosutinib, most commonly diarrhea (52%)., Conclusions: Bosutinib used in routine clinical practice in heavily pretreated patients with CML is an effective treatment for patients in CP and is generally tolerable., (© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)
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- 2022
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48. The implementation and validation of the NoMAD during a complex primary care intervention.
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Lamarche L, Clark RE, Parascandalo F, and Mangin D
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- Humans, Primary Health Care, Psychometrics, Surveys and Questionnaires, Family Health, Patient Care Team
- Abstract
Background: Normalization process theory (NPT) has been widely used to better understand how new interventions are implemented and embedded. The NoMAD (Normalization Measurement Development questionnaire) is a 23-item NPT instrument based on NPT. As the NoMAD is a relatively new instrument, the objectives of this paper are: to describe the experience of implementing the NoMAD, to describe it being used as a feedback mechanism to gain insight into the normalization process of a complex health intervention, and to further explore the psychometric properties of the instrument., Methods: Health TAPESTRY was implemented in six Family Health Teams (total of seven sites) across Ontario. Healthcare team members at each site were invited to complete the NoMAD, and three general questions about normalization, six times over a 12-month period. Each site was then provided a visual traffic light summary (TLS) reflecting the implementation of the Health TAPESTRY. The internal consistency of each sub-scale and validity of the NoMAD were assessed. Learnings from the implementation of the NoMAD and subsequent feedback mechanism (TLS) are reported descriptively., Results: In total, 56 diverse health care team members from six implementation sites completed the NoMAD. Each used it at least once during the 12-month study period. The implementation of the NoMAD and TLS was time consuming to do with multiple collection (and feedback) points. Most (60%) internal consistency values of the four subscales (pooled across site) across each collection point were satisfactory. All correlations were positive, and most (86%) were statistically significant among NoMAD subscales. All but one correlation between the NoMAD subscales and the general questions were positive, and most (72%) were significant. Generally, scores on the subscales were higher at 12-month than baseline, albeit did not follow a linear pattern of change across implementation. Generally, scores were higher for experienced sites compared to first-time implementors., Conclusion: Our experience would suggest fewer collection points; three timepoints spaced out by several months are adequate, if repeated administration of the NoMAD is used for feedback loops. We provide additional evidence of the psychometric properties of the NoMAD., Trial Registration: Registered at ClinicalTrials.gov: NCT03397836 ., (© 2022. The Author(s).)
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- 2022
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49. Development and implementation of a prescription opioid registry across diverse health systems.
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Ray GT, Altschuler A, Karmali R, Binswanger I, Glanz JM, Clarke CL, Ahmedani B, Andrade SE, Boscarino JA, Clark RE, Haller IV, Hechter R, Roblin DW, Sanchez K, Yarborough BJ, Bailey SR, McCarty D, Stephens KA, Rosa CL, Rubinstein AL, and Campbell CI
- Abstract
Objective: Develop and implement a prescription opioid registry in 10 diverse health systems across the US and describe trends in prescribed opioids between 2012 and 2018., Materials and Methods: Using electronic health record and claims data, we identified patients who had an outpatient fill for any prescription opioid, and/or an opioid use disorder diagnosis, between January 1, 2012 and December 31, 2018. The registry contains distributed files of prescription opioids, benzodiazepines and other select medications, opioid antagonists, clinical diagnoses, procedures, health services utilization, and health plan membership. Rates of outpatient opioid fills over the study period, standardized to health system demographic distributions, are described by age, gender, and race/ethnicity among members without cancer., Results: The registry includes 6 249 710 patients and over 40 million outpatient opioid fills. For the combined registry population, opioid fills declined from a high of 0.718 per member-year in 2013 to 0.478 in 2018, and morphine milligram equivalents (MMEs) per fill declined from 985 MMEs per fill in 2012 to 758 MMEs in 2018. MMEs per member declined from 692 MMEs per member in 2012 to 362 MMEs per member in 2018., Conclusion: This study established a population-based opioid registry across 10 diverse health systems that can be used to address questions related to opioid use. Initial analyses showed large reductions in overall opioid use per member among the combined health systems. The registry will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association.)
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- 2022
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50. The UK SPIRIT 1 trial in newly diagnosed chronic myeloid leukaemia.
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Gallipoli P, Clark RE, Byrne J, Apperley JF, Milojkovic D, Foroni L, Goldman JM, and O'Brien S
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- Fusion Proteins, bcr-abl, Humans, United Kingdom epidemiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myeloid
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- 2022
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