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2. The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Author

Walker, Simon M., Cox, Edward, Revill, Paul, Musiime, Victor, Bwakura?Dangarembizi, Mutsa, Mallewa, Jane, Cheruiyot, Priscilla, Maitland, Kathryn, Ford, Nathan, Gibb, Diana M., Walker, A Sarah, Soares, Marta, Mugyenyi, P, Kityo, C, Musiime, V, Wavamunno, P, Nambi, E, Ocitti, P, Ndigendawani, M, Kabahenda, S, Kemigisa, M, Acen, J, Olebo, D, Mpamize, G, Amone, A, Okweny, D, Mbonye, A, Nambaziira, F, Rweyora, A, Kangah, M, Kabaswahili, V, Abach, J, Abongomera, G, Omongin, J, Aciro, I, Philliam, A, Arach, B, Ocung, E, Amone, G, Miles, P, Adong, C, Tumsuiime, C, Kidega, P, Otto, B, Apio, F, Baleeta, K, Mukuye, A, Abwola, M, Ssennono, F, Baliruno, D, Tuhirwe, S, Namisi, R, Kigongo, F, Kikyonkyo, D, Mushahara, F, Tusiime, J, Musiime, A, Nankya, A, Atwongyeire, D, Sirikye, S, Mula, S, Noowe, N, Lugemwa, A, Kasozi, M, Mwebe, S, Atwine, L, Senkindu, T, Natuhurira, T, Katemba, C, Ninsiima, E, Acaku, M, Kyomuhangi, J, Ankunda, R, Tukwasibwe, D, Ayesiga, L, Hakim, J, Nathoo, K, Bwakura?Dangarembizi, M, Reid, A, Chidziva, E, Mhute, T, Tinago, Gc, Bhiri, J, Mudzingwa, S, Phiri, M, Steamer, J, Nhema, R, Warambwa, C, Musoro, G, Mutsai, S, Nemasango, B, Moyo, C, Chitongo, S, Rashirai, K, Vhembo, S, Mlambo, B, Nkomani, S, Ndemera, B, Willard, M, Berejena, C, Musodza, Y, Matiza, P, Mudenge, B, Guti, V, Etyang, A, Agutu, C, Berkley, J, Maitland, K, Njuguna, P, Mwaringa, S, Etyang, T, Awuondo, K, Wale, S, Shangala, J, Kithunga, J, Mwarumba, S, Maitha, S Said, Mutai, R, Lewa, M Lozi, Mwambingu, G, Mwanzu, A, Kalama, C, Latham, H, Shikuku, J, Fondo, A, Njogu, A, Khadenge, C, Mwakisha, B, Siika, A, Wools?Kaloustian, K, Nyandiko, W, Cheruiyot, P, Sudoi, A, Wachira, S, Meli, B, Karoney, M, Nzioka, A, Tanui, M, Mokaya, M, Ekiru, W, Mboya, C, Mwimali, D, Mengich, C, Choge, J, Injera, W, Njenga, K, Cherutich, S, Orido, M Anyango, Lwande, G Omondi, Rutto, P, Mudogo, A, Kutto, I, Shali, A, Jaika, L, Jerotich, H, Pierre, M, Mallewa, J, Kaunda, S, Van Oosterhout, J, O'Hare, B, Heydermann, R, Gonzalez, C, Dzabala, N, Kelly, C, Denis, B, Selemani, G, Mipando, L Nyondo, Chirwa, E, Banda, P, Mvula, L, Msuku, H, Ziwoya, M, Manda, Y, Nicholas, S, Masesa, C, Mwalukomo, T, Makhaza, L, Sheha, I, Bwanali, J, Limbuni, M, Gibb, D, Thomason, M, Walker, As, Pett, S, Szubert, A, Griffiths, A, Wilkes, H, Rajapakse, C, Spyer, M, Prendergast, A, Klein, N, Rauchenberger, M, Van Looy, N, Little, E, Fairbrother, K, Cowan, F, Seeley, J, Bernays, S, Kawuma, R, Mupambireyi, Z, Kyomuhendo, F, Nakalanzi, S, Peshu, J, Ndaa, S, Chabuka, J, Mkandawire, N, Matandika, L, Kapuya, C, Weller, I, Malianga, E, Mwansambo, C, Miiro, F, Elyanu, P, Bukusi, E, Katabira, E, Mugurungi, O, Peto, T, Musoke, P, Matenga, J, Phiri, S, Lyall, H, Johnston, V, Fitzgerald, F, Post, F, Ssali, F, Arenas?Pinto, A, Turkova, A, and Bamford, A

Subjects
Cost benefit analysis, Practice guidelines (Medicine) -- Evaluation, HIV infection -- Diagnosis -- Care and treatment, Cost benefit analysis, Health
Abstract

: Introduction: Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 Conclusions: The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices., Introduction In low‐ and middle‐income settings, more than a third of HIV‐positive individuals starting antiretroviral therapy (ART) present with advanced disease (CD4 ≤ 200 cells/mm[sup.3]); over half of these have [...]

Published
2020
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5. Transcranial Infrared Laser Stimulation Improves Cognition in Older Bipolar Patients: Proof of Concept Study.

Author

O'Donnell, Courtney M., Barrett, Douglas W., Fink, Latham H., Garcia-Pittman, Erica C., and Gonzalez-Lima, Francisco

Abstract

This is the first study to examine if transcranial infrared laser stimulation (TILS) improves cognition in older euthymic bipolar patients, who exhibit greater cognitive decline than is expected for age-matched controls. TILS is a non-invasive novel form of photobiomodulation that augments prefrontal oxygenation and improves cognition in young adults by upregulating the mitochondrial respiratory enzyme cytochrome-c-oxidase. We used a crossover sham-controlled design to examine if TILS to bilateral prefrontal cortex produces beneficial effects on cognition in 5 euthymic bipolar patients (ages 60-85). We measured cognitive flexibility, verbal fluency, working memory, sustained attention and impulsivity with tasks that have been shown to differentiate between healthy older adults and older bipolar adults. We found TILS-induced improvements in cognitive performance on the tasks that measure cognitive flexibility and impulsivity, after 5 weekly sessions of TILS. We concluded that TILS appeared both safe and effective in helping alleviate the accelerated cognitive decline present in older bipolar patients. [ABSTRACT FROM AUTHOR]

Published
2022
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7. Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial

Author

Kityo, C, Szubert, AJ, Siika, A, Heyderman, R, Bwakura-Dangarembizi, M, Lugemwa, A, Mwaringa, S, Griffiths, A, Nkanya, I, Kabahenda, S, Wachira, S, Musoro, G, Rajapakse, C, Etyang, T, Abach, J, Spyer, MJ, Wavamunno, P, Nyondo-Mipando, L, Chidziva, E, Nathoo, K, Klein, N, Hakim, J, Gibb, DM, Walker, AS, Pett, SL, Mugyenyi, P, Musiime, V, Nambi, E, Ocitti, P, Ndigendawani, M, Kemigisa, M, Acen, J, Olebo, D, Mpamize, G, Amone, A, Okweny, D, Mbonye, A, Nambaziira, F, Rweyora, A, Kangah, M, Kabaswahili, V, Abongomera, G, Omongin, J, Aciro, I, Philliam, A, Arach, B, Ocung, E, Amone, G, Miles, P, Adong, C, Tumsuiime, C, Kidega, P, Otto, B, Apio, F, Baleeta, K, Mukuye, A, Abwola, M, Ssennono, F, Baliruno, D, Tuhirwe, S, Namisi, R, Kigongo, F, Kikyonkyo, D, Mushahara, F, Tusiime, J, Musiime, A, Nankya, A, Atwongyeire, D, Sirikye, S, Mula, S, Noowe, N, Kasozi, M, Mwebe, S, Atwine, L, Senkindu, T, Natuhurira, T, Katemba, C, Ninsiima, E, Acaku, M, Kyomuhangi, J, Ankunda, R, Tukwasibwe, D, Ayesiga, L, Reid, A, Mhute, T, Tinago, GC, Bhiri, J, Mudzingwa, S, Phiri, M, Steamer, J, Nhema, R, Warambwa, C, Mutsai, S, Nemasango, B, Moyo, C, Chitongo, S, Rashirai, K, Vhembo, S, Mlambo, B, Nkomani, S, Ndemera, B, Willard, M, Berejena, C, Musodza, Y, Matiza, P, Mudenge, B, Guti, V, Etyang, A, Agutu, C, Berkley, J, Maitland, K, Njuguna, P, Awuondo, K, Wale, S, Shangala, J, Kithunga, J, Mwarumba, S, Maitha, SS, Mutai, R, Lewa, ML, Mwambingu, G, Mwanzu, A, Kalama, C, Latham, H, Shikuku, J, Fondo, A, Njogu, A, Khadenge, C, Mwakisha, B, Wools-Kaloustian, K, Nyandiko, W, Cheruiyot, P, Sudoi, A, Meli, B, Karoney, M, Nzioka, A, Tanui, M, Mokaya, M, Ekiru, W, Mboya, C, Mwimali, D, Mengich, C, Choge, J, Injera, W, Njenga, K, Cherutich, S, Orido, MA, Lwande, GO, Rutto, P, Mudogo, A, Kutto, I, Shali, A, Jaika, L, Jerotich, H, Pierre, M, Mallewa, J, Kaunda, S, Van Oosterhout, J, O'Hare, B, Heydermann, R, Gonzalez, C, Dzabala, N, Kelly, C, Denis, B, Selemani, G, Mipando, LN, Chirwa, E, Banda, P, Mvula, L, Msuku, H, Ziwoya, M, Manda, Y, Nicholas, S, Masesa, C, Mwalukomo, T, Makhaza, L, Sheha, I, Bwanali, J, Limbuni, M, and DiFDMRCWellcome Trust

Subjects
Adult, Male, Zimbabwe, Malawi, Adolescent, Anti-HIV Agents, BIOMARKERS, CHILDREN, HIV Infections, Drug Administration Schedule, Health Services Accessibility, IMMUNE RECONSTITUTION, EFAVIRENZ, Young Adult, Medicine, General & Internal, General & Internal Medicine, Raltegravir Potassium, INFECTION, Humans, Uganda, Child, 11 Medical and Health Sciences, RESTORATION, IMMUNODEFICIENCY, Science & Technology, MORTALITY, ADULTS, SOUTH-AFRICA, Kenya, Anti-Retroviral Agents, Child, Preschool, Africa, Disease Progression, Female, Life Sciences & Biomedicine, REALITY trial team, Follow-Up Studies
Abstract

Background In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events. Methods and findings In a 2×2×2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76–1.28], p = 0.91); in serious (aHR = 0.99 [0.81–1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71–1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63–1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9%] participants with raltegravir-intensified ART versus 86 [9.5%] with standard ART, p = 0.79) or in hospitalisations (aHR = 0.94 [95% CI 0.76–1.17], p = 0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance, respectively. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). Limitations of the study include limited clinical, radiological, and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. Conclusions Although 12 weeks of raltegravir intensification was well tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events in this group and is not warranted. There was no excess of IRIS-compatible events, suggesting that integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immunocompromised individuals. Trial registration ClinicalTrials.gov NCT01825031.

Published
2018

8. 37th International Symposium on Intensive Care and Emergency Medicine (part 1 of 3)

Author

Karavana, V., Smith, I., Kanellis, G., Sigala, I., Kinsella, T., Zakynthinos, S., Liu, L., Chen, J., Zhang, X., Liu, A., Guo, F., Liu, S., Yang, Y., Qiu, H., Grimaldi, D. G., Kaya, E., Acicbe, O., Kayaalp, I., Asar, S., Dogan, M., Eren, G., Hergunsel, O., Pavelescu, D., Grintescu, I., Mirea, L., Guanziroli, M., Gotti, M., Marino, A., Cressoni, M., Vergani, G., Chiurazzi, C., Chiumello, D., Gattinoni, L., Spano, S., Massaro, F., Moustakas, A., Johansson, S., Larsson, A., Perchiazzi, G., Zhang, X. W., Guo, F. M., Chen, J. X., Xue, M., Qiu, H. B., Yang, L., Fister, M., Knafelj, R., Suzer, M. A., Kavlak, M. E., Atalan, H. K., Gucyetmez, B., Cakar, N., Weller, D., Grootendorst, A. F., Dijkstra, A., Kuijper, T. M., Cleffken, B. I., Regli, A., De Keulenaer, B., Van Heerden, P., Hadfield, D., Hopkins, P. A., Penhaligon, B., Reid, F., Hart, N., Rafferty, G. F., Grasselli, G., Mauri, T., Lazzeri, M., Carlesso, E., Cambiaghi, B., Eronia, N., Maffezzini, E., Bronco, A., Abbruzzese, C., Rossi, N., Foti, G., Bellani, G., Pesenti, A., Bassi, G. Li, Panigada, M., Ranzani, O., Kolobow, T., Zanella, A., Berra, L., Parrini, V., Kandil, H., Salati, G., Livigni, S., Amatu, A., Girardis, M., Barbagallo, M., Moise, G., Mercurio, G., Costa, A., Vezzani, A., Lindau, S., Babel, J., Cavana, M., Torres, A., Ranzani, O. T., Umbrello, M., Taverna, M., Formenti, P., Mistraletti, G., Vetrone, F., Baisi, A., Garnero, A. G., Novotni, D. N., Arnal, J. A., Urner, M., Fan, E., Dres, M., Vorona, S., Brochard, L., Ferguson, N. D., Goligher, E. C., Leung, C., Joynt, G., Wong, W., Lee, A., Gomersall, C., Poels, S., Casaer, M., Schetz, M., Van den Berghe, G., Meyfroidt, G., Holzgraefe, B., Von Kobyletzki, L. B., Cianchi, G., Becherucci, F., Batacchi, S., Cozzolino, M., Franchi, F., Di Valvasone, S., Ferraro, M. C., Peris, A., Phiphitthanaban, H., Wacharasint, P., Wongsrichanalai, V., Lertamornpong, A., Pengpinij, O., Wattanathum, A., Oer-areemitr, N., Boddi, M., Cappellini, E., Ciapetti, M., Di Lascio, G., Bonizzoli, M., Lazzeri, C., Katsin, M. L., Hurava, M. Y., Dzyadzko, A. M., Hermann, A., Schellongowski, P., Bojic, A., Riss, K., Robak, O., Lamm, W., Sperr, W., Staudinger, T., Buoninsegni, L. Tadini, Parodo, J., Ottaviano, A., Cecci, L., Corsi, E., Ricca, V., de Garibay, A. Perez Ruiz, Ende-Schneider, B., Schreiber, C., Kreymann, B., Turani, F., Resta, M., Niro, D., Castaldi, P., Boscolo, G., Gonsales, G., Martini, S., Belli, A., Zamidei, L., Falco, M., Lamas, T., Mendes, J., Galazzi, A., Benco, B., Binda, F., Masciopinto, L., Lissoni, A., Adamini, I., Thamjamrassri, T., Watcharotayangul, J., Numthavaj, P., Kongsareepong, S., Higuera, J., Cabestrero, D., Rey, L., Narváez, G., Blandino, A., Aroca, M., Saéz, S., De Pablo, R., Mohamed, A., Sklar, M., Munshi, L., Alban, L., Turrini, C., Taccone, P., Marenghi, C., Spadaro, S., Volta, C., Alonso, D. Cabestrero, González, L. Rey, Franci, A., Stocchi, G., Cappuccini, G., Socci, F., Guetti, C., Rastrelli, P., Nestorowicz, A., Glapinski, J., Fijalkowska-Nestorowicz, A., Wosko, J., Duprez, F., Bonus, T., Cuvelier, G., Mashayekhi, S., Ollieuz, S., Reychler, G., Kuchyn, I., Bielka, K., Sergienko, A., Jones, H., Day, C., Park, S. C., Yeom, S. R., Myatra, S. N., Gupta, S., Rajnala, V., Divatia, J., Silva, J. Villalobos, Olvera, O. Aguilera, Schulte, R. Cavazos, Bermudez, M. Castañeda, Zorrilla, L. Pariente, Ferretis, H. Lopez, García, K. Trejo, Balciuniene, N., Ramsaite, J., Kriukelyte, O., Krikscionaitiene, A., Tamosuitis, T., Terragni, P., Brazzi, L., Falco, D., Pistidda, L., Magni, G., Bartoletti, L., Mascia, L., Filippini, C., Ranieri, V., Kyriakoudi, A., Rovina, N., Koltsida, O., Konstantellou, E., Kardara, M., Kostakou, E., Gavriilidis, G., Vasileiadis, I., Koulouris, N., Koutsoukou, A., Van Snippenburg, W., Kröner, A., Flim, M., Buise, M., Hemler, R., Spronk, P., Noffsinger, B., Singh, B., Hockings, L., Spina, C., Magni, F., Di Giambattista, C., Vargiolu, A., Citerio, G., Scaramuzzo, G., Waldmann, A. D., Böhm, S. H., Ragazzi, R., Volta, C. A., Heines, S. J., Strauch, U., Van de Poll, M. C., Roekaerts, P. M., Bergmans, D. C., Sosio, S., Gatti, S., Punzi, V., Asta, A., Mroczka, J., Yaroshetskiy, A. I, Rezepov, N. A., Mandel, I. A., Gelfand, B. R., Ozen, E., Karakoc, E., Ayyildiz, A., Kara, S., Ekemen, S., Yelken, B. Buyukkidan, Saasouh, W., Freeman, J., Turan, A., Hajjej, Z., Sellami, W., Bousselmi, M., Samoud, W., Gharsallah, H., Labbene, I., Ferjani, M., Vetrugno, L., Barbariol, F., Forfori, F., Regeni, I., Della Rocca, G., Jansen, D., Jonkman, A., Doorduin, J., Roesthuis, L., Van der Hoeven, J., Heunks, L., Marocco, S. Arrigoni, Bottiroli, M., Pinciroli, R., Galanti, V., Calini, A., Gagliardone, M., Fumagalli, R., Ippolito, D., Sala, V. L., Meroni, V., Elbanna, M., Nassar, Y., Abdelmohsen, A., Yahia, M., Mongodi, S., Mojoli, F., Via, G., Tavazzi, G., Fava, F., Pozzi, M., Iotti, G. A., Bouhemad, B., Ruiz-Ferron, F., Simón, J. Serrano, Gordillo-Resina, M., Chica-Saez, V., Garcia, M. Ruiz, Vela-Colmenero, R., Redondo-Orts, M., Gontijo-Coutinho, C., Ozahata, T., Nocera, P., Franci, D., Santos, T., Carvalho-Filho, M., Fochi, O., Nacoti, M., Signori, D., Bonacina, D., Bonanomi, E., Bonvecchio, E., Stella, A., Roldi, E., Orlando, A., Luperto, M., Trunfio, D., Licitra, G., Martinelli, R., Vannini, D., Giuliano, G., Näslund, E., Lindberg, L. G., Lund, I., Frithiof, R., Nichols, A., Pentakota, S., Kodali, B., Pranskunas, A., Kiudulaite, I., Simkiene, J., Damanskyte, D., Pranskuniene, Z., Arstikyte, J., Vaitkaitis, D., Pilvinis, V., Brazaitis, M., Pool, R., Haugaa, H., Botero, A., Escobar, D., Maberry, D., Tønnessen, T., Zuckerbraun, B., Pinsky, M., Gomez, H., Lyons, H., Trimmings, A., Domizi, R., Scorcella, C., Damiani, E., Pierantozzi, S., Tondi, S., Monaldi, V., Carletti, A., Zuccari, S., Adrario, E., Pelaia, P., Donati, A., Kazune, S., Grabovskis, A., Volceka, K., Rubins, U., Bol, M., Suverein, M., Delnoij, T., Driessen, R., Heines, S., Delhaas, T., Vd Poll, M., Sels, J., Jozwiak, M., Chambaz, M., Sentenac, P., Richard, C., Monnet, X., Teboul, J. L., Bitar, Z., Maadarani, O., Al Hamdan, R., Huber, W., Malbrain, M., Chew, M., Mallat, J., Tagami, T., Hundeshagen, S., Wolf, S., Mair, S., Schmid, R., Aron, J., Adlam, M., Dua, G., Mu, L., Chen, L., Yoon, J., Clermont, G., Dubrawski, A., Duhailib, Z., Al Assas, K., Shafquat, A., Salahuddin, N., Donaghy, J., Morgan, P., Valeanu, L., Stefan, M., Provenchere, S., Longrois, D., Shaw, A., Mythen, M. G., Shook, D., Hayashida, D., Munson, S. H., Sawyer, A., Mariyaselvam, M., Blunt, M., Young, P., Nakwan, N., Khwannimit, B., Checharoen, P., Berger, D., Moller, P., Bloechlinger, S., Bloch, A., Jakob, S., Takala, J., Van den Brule, J. M., Stolk, R., Vinke, E., Van Loon, L. M., Pickkers, P., Van der Hoeven, J. G., Kox, M., Hoedemaekers, C. W., Werner-Moller, P., Bertini, P., Guarracino, F., Colosimo, D., Gonnella, S., Brizzi, G., Mancino, G., Baldassarri, R., Pinsky, M. R., Amitrano, D., Goslar, T., Stajer, D., Radsel, P., De Vos, R., Dijk, N. Bussink-van, Stringari, G., Cogo, G., Devigili, A., Graziadei, M. Ceola, Bresadola, E., Lubli, P., Amella, S., Marani, F., Polati, E., Gottin, L., Colinas, L., Hernández, G., Vicho, R., Serna, M., Canabal, A., Cuena, R., Gimenez, J., Mercado, P., Depret, F., Sassi, K., Herner, A., Abded, N., Elghonemi, M., Monir, A., Nikhilesh, J., Apurv, T., Uber, A. U., Grossestreuer, A., Moskowitz, A., Patel, P., Holmberg, M. J., Donnino, M. W., Graham, C. A., Hung, K., Lo, R., Leung, L. Y., Lee, K. H., Yeung, C. Y., Chan, S. Y., Trembach, N., Zabolotskikh, I., Caldas, J., Panerai, R., Camara, L., Ferreira, G., Almeida, J., de Oliveira, G. Queiroz, Jardim, J., Bor-Seng-Shu, E., Lima, M., Nogueira, R., Jatene, F., Zeferino, S., Galas, F., Robinson, T., Hajjar, L. A., Oliveira, M., Norgueira, R., Groehs, R., Ferreira-Santos, L., Oliveira, G., Hajjar, L., Ribeiro, J., Gaiotto, F., Lisboa, L., Fukushima, J., Rizk, S., Osawa, E., Franco, R., Kalil, R., Chlabicz, M., Sobkowicz, B., Kaminski, K., Kazimierczyk, R., Musial, W., Tycińska, A., Siranovic, M., Gopcevic, A., Gavranovic, Z. G., Horvat, A. H., Krolo, H., Rode, B., Videc, L., Trifi, A., Abdellatif, S., Ismail, K. Ben, Bouattour, A., Daly, F., Nasri, R., Lakhal, S. Ben, Beurton, A., Girotto, V., Galarza, L., Guedj, T., Iliæ, M. Karaman, Sakic, L., NN, V., Stojcic, L., Alphonsine, J., Lai, C., Tapanwong, N., Chuntupama, P., Hoellthaler, J., Lahmer, T., Latham, H., Bengtson, C. D., Satterwhite, L., Stites, M., Simpson, S. Q., Skladzien, T., Cicio, M., Garlicki, J., Serednicki, W., Wordliczek, J., Vargas, P., Salazar, A., Espinoza, M., Graf, J., Kongpolprom, N., Sanguanwong, N., Jonnada, S., Gerrard, C., Jones, N., Morley, T., Thorburn, P. T., Musaeva, T., Horst, S., Lipcsey, M., Kawati, R., Pikwer, A., Rasmusson, J., Castegren, M., Shilova, A., Yafarova, A., Gilyarov, M., Stojiljkovic, D. L. Loncar, Ulici, A., Reidt, S., Lam, T., Jancik, J., Ragab, D., Taema, K., Farouk, W., Saad, M., Liu, X., Uber, A., Montissol, S., Donnino, M., Andersen, L. W., Perlikos, F., Lagiou, M., Papalois, A., Kroupis, C., Toumpoulis, I., Carter, D., Sardo, S., Landoni, G., Kongsayreepong, S., Sungsiri, R., Wongsripunetit, P., Marchio, P., Guerra-Ojeda, S., Gimeno-Raga, M., Mauricio, M. D., Valles, S. L., Aldasoro, C., Jorda, A., Aldasoro, M., Vila, J. M., Borg, U. B., Neitenbach, A. M., García, M., González, P. Guijo, Romero, M. Gracia, Orduña, P. Saludes, Cano, A. Gil, Rhodes, A., Grounds, R. M., Cecconi, M., Lee, C., Hatib, F., Jian, Z., Rinehart, J., De Los Santos, J., Canales, C., Cannesson, M., García, M. I. Monge, Scheeren, T., Chantziara, V., Vassi, A., Michaloudis, G., Sanidas, E., Golemati, S., Bateman, R. M., Mokhtar, A., Omar, W., Aziz, K. Abdel, El Azizy, H., Nielsen, D. L. Lykke, Holler, J. G., Lassen, A., Eriksson, M., Strandberg, G., Capoletto, C., Nakamura, R., Risk, S., Park, C., Dias, F., D’Arrigo, N., Fortuna, F., Redaelli, S., Zerman, L., Becker, L., Serrano, T., Cotes, L., Ramos, F., Fadel, L., Coelho, F., Mendes, C., Real, J., Pedron, B., Kuroki, M., Costa, E., and Azevedo, L.

Subjects
Critical Care and Intensive Care Medicine, Meeting Abstracts
Published
2017

11. PAPERS IN MECHANICS

Author

HOOKEY, WILLIAM, Sison, E., Sture, Wm., Body, G., HEDDERWICK, PETER, WILLIAMS, CHARLES, WOODALL, JOHN, Nash, William, LAURENCE, JOHN, BYRON, L., LEVIEN, M., WHITAKER, JOHN, NICHOLSON, PETER, Ward, Henry, BROTHERS, J., Beare, M., Horn, William, MARTIN, WILLIAM, DRURY, CHARLES, Hewett, Robert, Latham, H., Folsch, F., Stanhope, Lancaster, Joseph, Keyworth, Thomas, STONE, JAMES, WILSON, CHARLES, BOYCE, THOMAS, CLEGHORN, THOMAS, PERCY, SCOTT, GEORGE, and MILLER, JOHN

Published
1814

12. Rapid-Response Impulsivity: Definitions, Measurement Issues, and Clinical Implications

Author

Andrew K. Littlefield, F. Gerard Moeller, Victoria C. Wing, Carl W. Lejuez, Alan C. Swann, Luke Clark, Kathryn A. Cunningham, Scott D. Lane, Latham H. L. Fink, Noelle C. Anastasio, Kristen R. Hamilton, Marc N. Potenza, Christian G. Schütz, and Charles W. Mathias

Subjects
media_common.quotation_subject, Mental Disorders, Brain, Reproducibility of Results, Context (language use), Test validity, Impulsivity, medicine.disease, Personality disorders, Article, Developmental psychology, Psychiatry and Mental health, Clinical Psychology, Consistency (negotiation), Action (philosophy), Impulsive Behavior, medicine, Personality, Humans, medicine.symptom, Psychology, Construct (philosophy), human activities, media_common, Cognitive psychology
Abstract

Impulsivity is a multi-faceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity in the context of these conditions is limited by a lack of precision and consistency in its definition and assessment. Rapid-response-impulsivity (RRI) represents a tendency toward immediate action that occurs with diminished forethought and is out of context with the present demands of the environment. Experts from the International Society for Research on Impulsivity (InSRI) met to discuss and evaluate RRI-measures in terms of reliability, sensitivity, and validity with the goal of helping researchers and clinicians make informed decisions about the use and interpretation of findings from RRI-measures. Their recommendations are described in this manuscript. Commonly-used clinical and preclinical RRI-tasks are described, and considerations are provided to guide task selection. Tasks measuring two conceptually and neurobiologically distinct types of RRI, “refraining from action initiation” (RAI) and “stopping an ongoing action” (SOA) are described. RAI and SOA-tasks capture distinct aspects of RRI that may relate to distinct clinical outcomes. The InSRI group recommends that: 1) selection of RRI-measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; 2) researchers use both RAI and SOA tasks in RRI studies to allow for direct comparison of RRI types and examination of their associations with clinically relevant measures; and, 3) similar considerations should be made for human and non-human studies in an effort to harmonize and integrate pre-clinical and clinical research.

Published
2015

13. 5-HT2C receptor desensitization moderates anxiety in 5-HTT deficient mice: from behavioral to cellular evidence

Author

Rafael Maldonado, Kathryn A. Cunningham, Latham H. L. Fink, Caroline Chevarin, José Manuel Trigo, Laurence Lanfumey, Vincent Martin, Raymond Mongeau, Cédric B. P. Martin, and M. Hamon

Subjects
Agonist, Male, medicine.medical_specialty, Antidepressant drugs, medicine.drug_class, Serotonina, Stimulation, Pharmacology, Anxiety, Editing, Frontal cortex, Reuptake, Angoixa, Mice, Internal medicine, medicine, Receptor, Serotonin, 5-HT2C, Animals, Pharmacology (medical), Interpersonal Relations, RNA, Messenger, C-fos mRNA, Receptor, Cervell -- Metabolisme, Mice, Knockout, Serotonin Plasma Membrane Transport Proteins, Analysis of Variance, Behavior, Animal, Brain, Feeding Behavior, 3. Good health, Serotonin Receptor Agonists, 5-HT2C receptor, Mice, Inbred C57BL, Psychiatry and Mental health, Disease Models, Animal, Endocrinology, Anxiogenic, Gene Expression Regulation, Antidepressant, Reuptake inhibitor, Psychology, Serotonin2C, Proto-Oncogene Proteins c-fos, Research Article
Abstract

BACKGROUND: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. METHODS: Mice lacking the 5-HT reuptake carrier (5-HTT(-/-)) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR-induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos-induced expression) levels. RESULTS: Although 5-HTT(-/-) mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR-mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR-mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT(-/-) mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT(-/-) mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR-like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT(-/-) mutants. CONCLUSIONS: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT(-/-) mice. This work was supported by grants from INSERM, UPMC, the European Community (FP7, “Devanx” consortium, F2-2007–201714), and ANR (Sercedit 2008–2010, contract ANR-06-Neuro-045-01). Dr CBP Martin was recipient of a fellowship from the French Ministère de la Recherche during performance of this work. Dr Trigo was supported by Fundacion Alicia Koplowitz. Dr Fink (DA07287, DA034488) and Dr Cunningham (DA024157, DA020087) were supported by the National Institute on Drug Abuse grants

Published
2015

18. Functional Status of the Serotonin 5-HT2C Receptor (5-HT2CR) Drives Interlocked Phenotypes that Precipitate Relapse-Like Behaviors in Cocaine Dependence.

Author

Anastasio, Noelle C, Stutz, Sonja J, Fox, Robert G, Sears, Robert M, Emeson, Ronald B, DiLeone, Ralph J, O'Neil, Richard T, Fink, Latham H, Li, Dingge, Green, Thomas A, Gerard Moeller, F, and Cunningham, Kathryn A

Subjects
COCAINE, SEROTONIN receptors, DRUG addiction, PREFRONTAL cortex, MESSENGER RNA
Abstract

Relapse vulnerability in cocaine dependence is rooted in genetic and environmental determinants, and propelled by both impulsivity and the responsivity to cocaine-linked cues ('cue reactivity'). The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2C receptor (5-HT2CR) within the medial prefrontal cortex (mPFC) is uniquely poised to serve as a strategic nexus to mechanistically control these behaviors. The 5-HT2CR functional capacity is regulated by a number of factors including availability of active membrane receptor pools, the composition of the 5-HT2CR macromolecular protein complex, and editing of the 5-HT2CR pre-mRNA. The one-choice serial reaction time (1-CSRT) task was used to identify impulsive action phenotypes in an outbred rat population before cocaine self-administration and assessment of cue reactivity in the form of lever presses reinforced by the cocaine-associated discrete cue complex during forced abstinence. The 1-CSRT task reliably and reproducibly identified high impulsive (HI) and low impulsive (LI) action phenotypes; HI action predicted high cue reactivity. Lower cortical 5-HT2CR membrane protein levels concomitant with higher levels of 5-HT2CR:postsynaptic density 95 complex distinguished HI rats from LI rats. The frequency of edited 5-HT2CR mRNA variants was elevated with the prediction that the protein population in HI rats favors those isoforms linked to reduced signaling capacity. Genetic loss of the mPFC 5-HT2CR induced aggregate impulsive action/cue reactivity, suggesting that depressed cortical 5-HT2CR tone confers vulnerability to these interlocked behaviors. Thus, impulsive action and cue reactivity appear to neuromechanistically overlap in rodents, with the 5-HT2CR functional status acting as a neural rheostat to regulate, in part, the intersection between these vulnerability behaviors. [ABSTRACT FROM AUTHOR]

Published
2014
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42. Cheaper Without Seats?

Author

RAILTON, ARTHUR E., STERMAN, MARSHALL S., and LATHAM, H. S.

Subjects
TARIFF, VOLKSWAGEN trucks
Abstract

Several letters to the editor are presented about an article on the impact of the increase in tariff on trucks on automotive maker Volkswagen in the July 15, 1964 issue.

Published
1964

45. 5-HT2C Receptor Desensitization Moderates Anxiety in 5-HTT Deficient Mice: From Behavioral to Cellular Evidence.

Author

Martin, Cédric BP, Martin, Vincent S., Trigo, José M., Chevarin, Caroline, Maldonado, Rafael, Fink, Latham H., Cunningham, Kathryn A., Hamon, Michel, Lanfumey, Laurence, and Mongeau, Raymond

Subjects
ANXIETY, ANTIDEPRESSANTS, SEROTONIN receptors, DESENSITIZATION (Psychotherapy), BRAIN anatomy, MESSENGER RNA
Abstract

Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice. [ABSTRACT FROM AUTHOR]

Published
2015

50. Advance planning for co-caring couples.

Author

Lezard R and Latham H

Subjects
Humans, Compassion Fatigue, Caregivers
Abstract

This article explores joint advance planning for co-caring couples in the community, a group growing in number and need. A health crisis for one, exposes the vulnerability of the other. Lack of planning for this eventuality leaves health and social care struggling to provide an adequate safety net in a short timeframe. This inability to adequately support, can lead to harm to the couple. The authors conducted a formal reflective investigation to discover themes that impacted on their ability to meet the needs of such a couple in their care. The themes were: the need for advanced care planning in co-caring situations; capacity assessed through different lenses; using safeguarding systems appropriately to support questions of capacity; challenges when care is not accepted; and compassion fatigue. These themes were then used to develop an action plan to improve ways of working to reduce risk in these situations.

Published
2023
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