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Matthew P. Fox - One of the best experts on this subject based on the ideXlab platform.
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Changes in second-line regimen durability and continuity of care in relation to national ART guideline changes in South Africa.
Journal of the International AIDS Society, 2016Co-Authors: Dorina Onoya, Alana T. Brennan, Rebecca Berhanu, Liudmyla Van Der Berg, Thulasizwe Buthelezi, Matthew P. FoxAbstract:Little is known about the impact of antiretroviral therapy (ART) guideline changes on the durability of second-line ART and continuity of care. This study examines predictors of early Drug Substitutions and treatment interruptions using a cohort analysis of HIV positive adults switched to second-line ART between January 2004 and September 2013 in Johannesburg, South Africa. The main outcomes were having a Drug Substitution or treatment interruption in the first 24 months on second-line ART. Kaplan Meiers analyses and Cox proportional hazards regression were used to identify predictors of Drug Substitutions and treatment interruptions. Of 3028 patients on second-line ART, 353 (11.7%) had a Drug Substitution (8.6 per 100PY, 95% CI: 7.8-9.6) and 260 (8.6%) had a treatment interruption (6.3 per 100PY, 95% CI: 5.6-7.1). While treatment interruptions decreased from 32.5 per 100PY for the 2004 cohort to 2.3 per 100PY for the 2013 cohort, the rates of Drug Substitutions steadily increased, peaking at an incidence of 26.7 per 100PY for the 2009 cohort and then decreased to 4.2 per 100PY in the 2011 cohort. Compared to the 2004 to 2008 cohorts, the hazard of early Drug Substitutions was highest among patients switched to AZT + ddI + LPVr in 2009 to 2010 (aHR 5.1, 95% CI: 3.4-7.1) but remained low over time among patients switched to TDF + 3TC/FTC + LPVr or AZT/ABC + 3TC + LPVr. The main common predictor of both treatment interruption and Drug Substitution was Drug toxicity. Our results show a rapid transition between 2004 and 2010 ART guidelines and concurrent improvements in continuity of care among second-line ART patients. Drug toxicity reporting and monitoring systems need improvements to inform timely regimen changes and ensure that patients remain in care. However, reasons for Drug Substitutions should be closely monitored to ensure that patients do not run out of treatment options in the future.
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Increases in regimen durability associated with the introduction of tenofovir at a large public-sector clinic in Johannesburg, South Africa.
Journal of the International AIDS Society, 2013Co-Authors: Alana T. Brennan, Mhairi Maskew, Prudence Ive, Kate Shearer, Lawrence Long, Ian Sanne, Matthew P. FoxAbstract:In April 2010, tenofovir replaced stavudine in public-sector first-line antiretroviral therapy (ART) in South Africa. The association of tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir-based regimens. We evaluated changes over time in regimen durability at the Themba Lethu Clinic, Johannesburg, South Africa. This was a cohort analysis of treatment-naïve, non-pregnant adult patients initiated on ART between April 2004 and December 2011. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir was substituted for stavudine after April 2010. We evaluated the frequency and type of single-Drug Substitutions (excluding switches to second-line therapy). Cox models were used to evaluate the association of ART initiation year and antiretroviral Drug type with single-Drug Substitutions in the first 12 months on treatment. One thousand nine hundred and sixty-four (10%) Substitutions occurred amongst 19,699 patients. Excluding 2004 (year of treatment roll-out), before 2010 one-year single-Drug Substitutions ranged from 10.0 to 13.1%. In 2011, well after integration of tenofovir, Substitutions decreased to 5.6%. Single-Drug Substitution was lowest amongst patients on tenofovir (5.1%) versus zidovudine (11.3%), 30 mg stavudine (10.5%) or 40 mg stavudine (14.4%). Adjusted Cox models showed that patients initiating treatment between 2005 and 2010 (vs. 2011) had a twofold increased hazard of single-Drug Substitution, while those on zidovudine or stavudine had a two to threefold increase in single-Drug Substitution versus tenofovir patients in the first 12 months on ART. The decline in single-Drug Substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.
Peter A. Meredith - One of the best experts on this subject based on the ideXlab platform.
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bioequivalence and other unresolved issues in generic Drug Substitution
Clinical Therapeutics, 2003Co-Authors: Peter A. MeredithAbstract:Abstract Background: Substitution of generic Drugs for brand-name products is highly controversial and often is met with suspicion by health care providers and patients. Historically, the debate has focused on the issue of bioequivalence, and clinical practice has identified a number of Drug classes for which generic Substitution should be approached with caution. Current bioequivalence requirements are based on a measure of average bioequivalence; however, there are fears that use of this measure may be inappropriate in the case of a Drug with a narrow or wide therapeutic range or high intrasubject or intersubject variability. Under these circumstances, measures of individual and population bioequivalence are proposed to be more accurate than measures of average bioequivalence. Objective: This paper addresses issues of bioequivalence and other concerns with generic Drug Substitution. Methods: I conducted a MEDLINE search of the English-language literature containing the key terms generic, multisource, quality , and brand and published between 1973 and 2003. The names of branded pharmaceuticals whose patents had recently expired (eg, Ventolin HFA®, Adalat®, Capoten®, Tagamet HB 200®, and Valium®) also were used to search for articles on generic Substitution. Reference lists of relevant articles also were searched. Bioequivalence issues are presented together with more general concerns over generic Drug Substitution, such as consumer perception of risk, differences in product and packaging appearance, and differences in excipients. Results: The literature reviewed act to highlight a number of different Drug categories and patient subpopulations for which generic Substitution can still prove to be problematic. Conclusion: I recommend that health care providers continue to exercise caution in the consideration of generic Drug Substitution under certain circumstances.
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Bioequivalence and other unresolved issues in generic Drug Substitution.
Clinical therapeutics, 2003Co-Authors: Peter A. MeredithAbstract:Substitution of generic Drugs for brand-name products is highly controversial and often is met with suspicion by health care providers and patients. Historically, the debate has focused on the issue of bioequivalence, and clinical practice has identified a number of Drug classes for which generic Substitution should be approached with caution. Current bioequivalence requirements are based on a measure of average bioequivalence; however, there are fears that use of this measure may be inappropriate in the case of a Drug with a narrow or wide therapeutic range or high intrasubject or intersubject variability. Under these circumstances, measures of individual and population bioequivalence are proposed to be more accurate than measures of average bioequivalence. This paper addresses issues of bioequivalence and other concerns with generic Drug Substitution. I conducted a MEDLINE search of the English-language literature containing the key terms generic, multisource, quality, and brand and published between 1973 and 2003. The names of branded pharmaceuticals whose patents had recently expired (eg, Ventolin HFA, Adalat, Capoten, Tagamet HB 200, and Valium) also were used to search for articles on generic Substitution. Reference lists of relevant articles also were searched. Bioequivalence issues are presented together with more general concerns over generic Drug Substitution, such as consumer perception of risk, differences in product and packaging appearance, and differences in excipients. The literature reviewed act to highlight a number of different Drug categories and patient subpopulations for which generic Substitution can still prove to be problematic. I recommend that health care providers continue to exercise caution in the consideration of generic Drug Substitution under certain circumstances.
Dominique Paulus - One of the best experts on this subject based on the ideXlab platform.
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Drug Substitution associated with a hospital stay in belgium a retrospective analysis of a claims database
International Journal of Pharmacy Practice, 2014Co-Authors: Steven Simoens, Cécile Dubois, Anne Spinewine, Veerle Foulon, Dominique PaulusAbstract:Objectives: This study measures the extent of Drug Substitution associated with a hospital stay in Belgium. Methods: Data were extracted from the 2006-2007 dataset of the Belgian Agency of Health Insurance Funds on Drug use of patients hospitalized in acute hospitals. Reimbursed Drugs received in ambulatory care during the 3 months prior to hospitalization were compared with Drugs received during the 3 months following hospital discharge. Both a narrow definition and a broad definition were used for Drug Substitution. Narrow Substitution (switches between generic and originator Drugs) was computed for 14 Drug classes for chronic conditions with the highest public expenditure. Broad Substitution (changes between chemical substances within the Drug class at ATC level 4, changes in brand name) was calculated for statins and proton-pump inhibitors only. Key findings: The database included 17764 patients (mean age 66±17 years; 60% female). In 71% of cases an originator Drug was received prior to and following hospitalization. A generic Drug was received prior to and following hospitalization in 25% of cases. Some form of narrow Substitution occurred in 4% of cases: a generic Drug was replaced by an originator Drug in 2% of cases and an originator Drug was replaced by a generic Drug in 2% of cases. Some form of broad Substitution occurred in 25% of cases for proton-pump inhibitors and 13% of cases for statins. Conclusions: Hospitalization was not a trigger for changes between originator and generic versions of a Drug. Broad Substitution associated with a hospital stay was relatively limited for statins and proton-pump inhibitors. © 2013 Royal Pharmaceutical Society.
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Drug Substitution associated with a hospital stay in Belgium: a retrospective analysis of a claims database
The International journal of pharmacy practice, 2013Co-Authors: Steven Simoens, Cécile Dubois, Anne Spinewine, Veerle Foulon, Dominique PaulusAbstract:This study measures the extent of Drug Substitution associated with a hospital stay in Belgium. Data were extracted from the 2006-2007 dataset of the Belgian Agency of Health Insurance Funds on Drug use of patients hospitalized in acute hospitals. Reimbursed Drugs received in ambulatory care during the 3 months prior to hospitalization were compared with Drugs received during the 3 months following hospital discharge. Both a narrow definition and a broad definition were used for Drug Substitution. Narrow Substitution (switches between generic and originator Drugs) was computed for 14 Drug classes for chronic conditions with the highest public expenditure. Broad Substitution (changes between chemical substances within the Drug class at ATC level 4, changes in brand name) was calculated for statins and proton-pump inhibitors only. The database included 17 764 patients (mean age 66 ± 17 years; 60% female). In 71% of cases an originator Drug was received prior to and following hospitalization. A generic Drug was received prior to and following hospitalization in 25% of cases. Some form of narrow Substitution occurred in 4% of cases: a generic Drug was replaced by an originator Drug in 2% of cases and an originator Drug was replaced by a generic Drug in 2% of cases. Some form of broad Substitution occurred in 25% of cases for proton-pump inhibitors and 13% of cases for statins. Hospitalization was not a trigger for changes between originator and generic versions of a Drug. Broad Substitution associated with a hospital stay was relatively limited for statins and proton-pump inhibitors. © 2013 Royal Pharmaceutical Society.
Alana T. Brennan - One of the best experts on this subject based on the ideXlab platform.
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Changes in second-line regimen durability and continuity of care in relation to national ART guideline changes in South Africa.
Journal of the International AIDS Society, 2016Co-Authors: Dorina Onoya, Alana T. Brennan, Rebecca Berhanu, Liudmyla Van Der Berg, Thulasizwe Buthelezi, Matthew P. FoxAbstract:Little is known about the impact of antiretroviral therapy (ART) guideline changes on the durability of second-line ART and continuity of care. This study examines predictors of early Drug Substitutions and treatment interruptions using a cohort analysis of HIV positive adults switched to second-line ART between January 2004 and September 2013 in Johannesburg, South Africa. The main outcomes were having a Drug Substitution or treatment interruption in the first 24 months on second-line ART. Kaplan Meiers analyses and Cox proportional hazards regression were used to identify predictors of Drug Substitutions and treatment interruptions. Of 3028 patients on second-line ART, 353 (11.7%) had a Drug Substitution (8.6 per 100PY, 95% CI: 7.8-9.6) and 260 (8.6%) had a treatment interruption (6.3 per 100PY, 95% CI: 5.6-7.1). While treatment interruptions decreased from 32.5 per 100PY for the 2004 cohort to 2.3 per 100PY for the 2013 cohort, the rates of Drug Substitutions steadily increased, peaking at an incidence of 26.7 per 100PY for the 2009 cohort and then decreased to 4.2 per 100PY in the 2011 cohort. Compared to the 2004 to 2008 cohorts, the hazard of early Drug Substitutions was highest among patients switched to AZT + ddI + LPVr in 2009 to 2010 (aHR 5.1, 95% CI: 3.4-7.1) but remained low over time among patients switched to TDF + 3TC/FTC + LPVr or AZT/ABC + 3TC + LPVr. The main common predictor of both treatment interruption and Drug Substitution was Drug toxicity. Our results show a rapid transition between 2004 and 2010 ART guidelines and concurrent improvements in continuity of care among second-line ART patients. Drug toxicity reporting and monitoring systems need improvements to inform timely regimen changes and ensure that patients remain in care. However, reasons for Drug Substitutions should be closely monitored to ensure that patients do not run out of treatment options in the future.
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Increases in regimen durability associated with the introduction of tenofovir at a large public-sector clinic in Johannesburg, South Africa.
Journal of the International AIDS Society, 2013Co-Authors: Alana T. Brennan, Mhairi Maskew, Prudence Ive, Kate Shearer, Lawrence Long, Ian Sanne, Matthew P. FoxAbstract:In April 2010, tenofovir replaced stavudine in public-sector first-line antiretroviral therapy (ART) in South Africa. The association of tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir-based regimens. We evaluated changes over time in regimen durability at the Themba Lethu Clinic, Johannesburg, South Africa. This was a cohort analysis of treatment-naïve, non-pregnant adult patients initiated on ART between April 2004 and December 2011. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir was substituted for stavudine after April 2010. We evaluated the frequency and type of single-Drug Substitutions (excluding switches to second-line therapy). Cox models were used to evaluate the association of ART initiation year and antiretroviral Drug type with single-Drug Substitutions in the first 12 months on treatment. One thousand nine hundred and sixty-four (10%) Substitutions occurred amongst 19,699 patients. Excluding 2004 (year of treatment roll-out), before 2010 one-year single-Drug Substitutions ranged from 10.0 to 13.1%. In 2011, well after integration of tenofovir, Substitutions decreased to 5.6%. Single-Drug Substitution was lowest amongst patients on tenofovir (5.1%) versus zidovudine (11.3%), 30 mg stavudine (10.5%) or 40 mg stavudine (14.4%). Adjusted Cox models showed that patients initiating treatment between 2005 and 2010 (vs. 2011) had a twofold increased hazard of single-Drug Substitution, while those on zidovudine or stavudine had a two to threefold increase in single-Drug Substitution versus tenofovir patients in the first 12 months on ART. The decline in single-Drug Substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.
Karen R. Jacobson - One of the best experts on this subject based on the ideXlab platform.
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Switching to bedaquiline for treatment of rifampicin-resistant tuberculosis in South Africa: A retrospective cohort analysis.
PloS one, 2019Co-Authors: Tara C. Bouton, Margaretha De Vos, Elizabeth J. Ragan, Laura F. White, Leonie Van Zyl, Danie Theron, C. Robert Horsburgh, Robin M. Warren, Karen R. JacobsonAbstract:South Africa led the world with guidelines on bedaquiline (BDQ) use as a single Drug Substitution to manage rifampin resistant tuberculosis regimen toxicity. We examined reasons for giving BDQ in a retrospective cohort: >75% of patients were switched to BDQ for toxicity (ototoxicity or renal dysfunction) rather than Drug resistance.
