The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Walter H. Dzik - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial gene sequence variants in children with severe malaria anaemia with or without Lactic Acidosis a case control study
Malaria Journal, 2018Co-Authors: Casey Fowler, Aggrey Dhabangi, Christine Csertigazdewich, Charles Musoke, Himanshu Sharma, Sami S Amr, Walter H. DzikAbstract:Evolutionary pressure by Plasmodium falciparum malaria is known to have favoured a large number of human gene adaptations, but there is surprisingly little investigation of the effect of malaria on human mitochondrial sequence variation. Plasmodium falciparum infection can cause severe malaria anaemia (SMA) with insufficient tissue oxygenation, Lactic Acidosis and death. Despite equal degrees of severe anaemia, some individuals develop Lactic Acidosis while others do not. A case–control study design was used to investigate whether differences in host mitochondrial gene sequences were associated with Lactic Acidosis in SMA. Full mitochondrial sequences were obtained from 36 subjects with SMA complicated by Lactic Acidosis and 37 subjects with SMA without Lactic Acidosis. The two groups were matched for age, sex, and degree of anaemia. Compared with the reference sequence, a median of 60 nucleotide variants per individual (interquartile range 4–91) was found, with an average frequency of 3.97 variants per 1000 nucleotides. The frequency and distribution of non-synonymous DNA variants in genes associated with oxidative phosphorylation were not statistically different between the two groups. Non-synonymous variants predicted to have the most disruptive effect on proteins responsible for oxidative phosphorylation were present at a similar frequency in both groups. Lactic Acidosis in SMA does not appear to be consistently associated with the high prevalence of any mitochondrial gene variant.
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mitochondrial gene sequence variants in children with severe malaria anaemia with or without Lactic Acidosis a case control study
Malaria Journal, 2018Co-Authors: Casey Fowler, Aggrey Dhabangi, Christine Csertigazdewich, Charles Musoke, Himanshu Sharma, Sami S Amr, Walter H. DzikAbstract:Background Evolutionary pressure by Plasmodium falciparum malaria is known to have favoured a large number of human gene adaptations, but there is surprisingly little investigation of the effect of malaria on human mitochondrial sequence variation. Plasmodium falciparum infection can cause severe malaria anaemia (SMA) with insufficient tissue oxygenation, Lactic Acidosis and death. Despite equal degrees of severe anaemia, some individuals develop Lactic Acidosis while others do not. A case–control study design was used to investigate whether differences in host mitochondrial gene sequences were associated with Lactic Acidosis in SMA. Full mitochondrial sequences were obtained from 36 subjects with SMA complicated by Lactic Acidosis and 37 subjects with SMA without Lactic Acidosis. The two groups were matched for age, sex, and degree of anaemia.
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the effect of blood storage age on treatment of Lactic Acidosis by transfusion in children with severe malarial anaemia a pilot randomized controlled trial
Malaria Journal, 2013Co-Authors: Aggrey Dhabangi, Edison Mworozi, Irene R Lubega, Christine Csertigazdewich, Albert Maganda, Walter H. DzikAbstract:Background Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated Lactic Acidosis. Lactic Acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of Lactic Acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of Lactic Acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial.
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the effect of blood storage age on treatment of Lactic Acidosis by transfusion in children with severe malarial anaemia a pilot randomized controlled trial
Malaria Journal, 2013Co-Authors: Aggrey Dhabangi, Edison Mworozi, Irene R Lubega, Christine Csertigazdewich, Albert Maganda, Walter H. DzikAbstract:Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated Lactic Acidosis. Lactic Acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of Lactic Acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of Lactic Acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin ≤ 5 g/dL) and Lactic Acidosis (blood lactate ≥5 mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21–35 days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose Lactic Acidosis resolved by four hours after transfusion. Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5 mmol/L by four hours post transfusion (p value = 0.308). The mean time to Lactic Acidosis resolution was 2.65 hours (95% CI; 2.25–3.05) in the short storage arm, compared to 3.35 hours (95% CI; 2.60–4.10) in the long storage arm (p value = 0.264). Pilot data suggest that among children with severe malarial anaemia and Lactic Acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of Lactic Acidosis. The results support a larger and well-powered study which is under way. clinicaltrials.gov NCT01580111
Aggrey Dhabangi - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial gene sequence variants in children with severe malaria anaemia with or without Lactic Acidosis a case control study
Malaria Journal, 2018Co-Authors: Casey Fowler, Aggrey Dhabangi, Christine Csertigazdewich, Charles Musoke, Himanshu Sharma, Sami S Amr, Walter H. DzikAbstract:Evolutionary pressure by Plasmodium falciparum malaria is known to have favoured a large number of human gene adaptations, but there is surprisingly little investigation of the effect of malaria on human mitochondrial sequence variation. Plasmodium falciparum infection can cause severe malaria anaemia (SMA) with insufficient tissue oxygenation, Lactic Acidosis and death. Despite equal degrees of severe anaemia, some individuals develop Lactic Acidosis while others do not. A case–control study design was used to investigate whether differences in host mitochondrial gene sequences were associated with Lactic Acidosis in SMA. Full mitochondrial sequences were obtained from 36 subjects with SMA complicated by Lactic Acidosis and 37 subjects with SMA without Lactic Acidosis. The two groups were matched for age, sex, and degree of anaemia. Compared with the reference sequence, a median of 60 nucleotide variants per individual (interquartile range 4–91) was found, with an average frequency of 3.97 variants per 1000 nucleotides. The frequency and distribution of non-synonymous DNA variants in genes associated with oxidative phosphorylation were not statistically different between the two groups. Non-synonymous variants predicted to have the most disruptive effect on proteins responsible for oxidative phosphorylation were present at a similar frequency in both groups. Lactic Acidosis in SMA does not appear to be consistently associated with the high prevalence of any mitochondrial gene variant.
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mitochondrial gene sequence variants in children with severe malaria anaemia with or without Lactic Acidosis a case control study
Malaria Journal, 2018Co-Authors: Casey Fowler, Aggrey Dhabangi, Christine Csertigazdewich, Charles Musoke, Himanshu Sharma, Sami S Amr, Walter H. DzikAbstract:Background Evolutionary pressure by Plasmodium falciparum malaria is known to have favoured a large number of human gene adaptations, but there is surprisingly little investigation of the effect of malaria on human mitochondrial sequence variation. Plasmodium falciparum infection can cause severe malaria anaemia (SMA) with insufficient tissue oxygenation, Lactic Acidosis and death. Despite equal degrees of severe anaemia, some individuals develop Lactic Acidosis while others do not. A case–control study design was used to investigate whether differences in host mitochondrial gene sequences were associated with Lactic Acidosis in SMA. Full mitochondrial sequences were obtained from 36 subjects with SMA complicated by Lactic Acidosis and 37 subjects with SMA without Lactic Acidosis. The two groups were matched for age, sex, and degree of anaemia.
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the effect of blood storage age on treatment of Lactic Acidosis by transfusion in children with severe malarial anaemia a pilot randomized controlled trial
Malaria Journal, 2013Co-Authors: Aggrey Dhabangi, Edison Mworozi, Irene R Lubega, Christine Csertigazdewich, Albert Maganda, Walter H. DzikAbstract:Background Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated Lactic Acidosis. Lactic Acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of Lactic Acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of Lactic Acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial.
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the effect of blood storage age on treatment of Lactic Acidosis by transfusion in children with severe malarial anaemia a pilot randomized controlled trial
Malaria Journal, 2013Co-Authors: Aggrey Dhabangi, Edison Mworozi, Irene R Lubega, Christine Csertigazdewich, Albert Maganda, Walter H. DzikAbstract:Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated Lactic Acidosis. Lactic Acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of Lactic Acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of Lactic Acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin ≤ 5 g/dL) and Lactic Acidosis (blood lactate ≥5 mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21–35 days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose Lactic Acidosis resolved by four hours after transfusion. Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5 mmol/L by four hours post transfusion (p value = 0.308). The mean time to Lactic Acidosis resolution was 2.65 hours (95% CI; 2.25–3.05) in the short storage arm, compared to 3.35 hours (95% CI; 2.60–4.10) in the long storage arm (p value = 0.264). Pilot data suggest that among children with severe malarial anaemia and Lactic Acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of Lactic Acidosis. The results support a larger and well-powered study which is under way. clinicaltrials.gov NCT01580111
Christine Csertigazdewich - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial gene sequence variants in children with severe malaria anaemia with or without Lactic Acidosis a case control study
Malaria Journal, 2018Co-Authors: Casey Fowler, Aggrey Dhabangi, Christine Csertigazdewich, Charles Musoke, Himanshu Sharma, Sami S Amr, Walter H. DzikAbstract:Evolutionary pressure by Plasmodium falciparum malaria is known to have favoured a large number of human gene adaptations, but there is surprisingly little investigation of the effect of malaria on human mitochondrial sequence variation. Plasmodium falciparum infection can cause severe malaria anaemia (SMA) with insufficient tissue oxygenation, Lactic Acidosis and death. Despite equal degrees of severe anaemia, some individuals develop Lactic Acidosis while others do not. A case–control study design was used to investigate whether differences in host mitochondrial gene sequences were associated with Lactic Acidosis in SMA. Full mitochondrial sequences were obtained from 36 subjects with SMA complicated by Lactic Acidosis and 37 subjects with SMA without Lactic Acidosis. The two groups were matched for age, sex, and degree of anaemia. Compared with the reference sequence, a median of 60 nucleotide variants per individual (interquartile range 4–91) was found, with an average frequency of 3.97 variants per 1000 nucleotides. The frequency and distribution of non-synonymous DNA variants in genes associated with oxidative phosphorylation were not statistically different between the two groups. Non-synonymous variants predicted to have the most disruptive effect on proteins responsible for oxidative phosphorylation were present at a similar frequency in both groups. Lactic Acidosis in SMA does not appear to be consistently associated with the high prevalence of any mitochondrial gene variant.
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mitochondrial gene sequence variants in children with severe malaria anaemia with or without Lactic Acidosis a case control study
Malaria Journal, 2018Co-Authors: Casey Fowler, Aggrey Dhabangi, Christine Csertigazdewich, Charles Musoke, Himanshu Sharma, Sami S Amr, Walter H. DzikAbstract:Background Evolutionary pressure by Plasmodium falciparum malaria is known to have favoured a large number of human gene adaptations, but there is surprisingly little investigation of the effect of malaria on human mitochondrial sequence variation. Plasmodium falciparum infection can cause severe malaria anaemia (SMA) with insufficient tissue oxygenation, Lactic Acidosis and death. Despite equal degrees of severe anaemia, some individuals develop Lactic Acidosis while others do not. A case–control study design was used to investigate whether differences in host mitochondrial gene sequences were associated with Lactic Acidosis in SMA. Full mitochondrial sequences were obtained from 36 subjects with SMA complicated by Lactic Acidosis and 37 subjects with SMA without Lactic Acidosis. The two groups were matched for age, sex, and degree of anaemia.
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the effect of blood storage age on treatment of Lactic Acidosis by transfusion in children with severe malarial anaemia a pilot randomized controlled trial
Malaria Journal, 2013Co-Authors: Aggrey Dhabangi, Edison Mworozi, Irene R Lubega, Christine Csertigazdewich, Albert Maganda, Walter H. DzikAbstract:Background Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated Lactic Acidosis. Lactic Acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of Lactic Acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of Lactic Acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial.
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the effect of blood storage age on treatment of Lactic Acidosis by transfusion in children with severe malarial anaemia a pilot randomized controlled trial
Malaria Journal, 2013Co-Authors: Aggrey Dhabangi, Edison Mworozi, Irene R Lubega, Christine Csertigazdewich, Albert Maganda, Walter H. DzikAbstract:Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated Lactic Acidosis. Lactic Acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of Lactic Acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of Lactic Acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin ≤ 5 g/dL) and Lactic Acidosis (blood lactate ≥5 mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21–35 days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose Lactic Acidosis resolved by four hours after transfusion. Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5 mmol/L by four hours post transfusion (p value = 0.308). The mean time to Lactic Acidosis resolution was 2.65 hours (95% CI; 2.25–3.05) in the short storage arm, compared to 3.35 hours (95% CI; 2.60–4.10) in the long storage arm (p value = 0.264). Pilot data suggest that among children with severe malarial anaemia and Lactic Acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of Lactic Acidosis. The results support a larger and well-powered study which is under way. clinicaltrials.gov NCT01580111
Edwin E. Salpeter - One of the best experts on this subject based on the ideXlab platform.
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risk of fatal and nonfatal Lactic Acidosis with metformin use in type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2010Co-Authors: Shelley R Salpeter, Elizabeth Greyber, Gary A Pasternak, Edwin E. SalpeterAbstract:BACKGROUND: Metformin is an oral anti-hyperglycemic agent used in the treatment of type 2 diabetes mellitus. The results of the UK Prospective Diabetes Study indicate that metformin treatment is associated with a reduction in total mortality compared to other anti-hyperglycemic treatments. Metformin, however, is thought to increase the risk of Lactic Acidosis, and is considered to be contraindicated in many chronic hypoxemic conditions that may be associated with Lactic Acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. OBJECTIVES: To assess the incidence of fatal and nonfatal Lactic Acidosis with metformin use compared to placebo and other glucose-lowering treatments in patients with type 2 diabetes mellitus. A secondary objective was to evaluate the blood lactate levels for those on metformin treatment compared to placebo or non-metformin therapies. SEARCH STRATEGY: A search was performed of the Cochrane Controlled Trials Register and the Database of Abstracts of Reviews of Effectiveness (up to 4/2000), Medline (up to 11/2000), Embase (up to 11/2000), Oldmedline, and Reactions (up to 5/2000), in order to identify all studies of metformin treatment from 1966 to November 2000. The Cumulated Index Medicus was used to search relevant articles from 1959 to 1965. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Date of latest search: November 2000. SELECTION CRITERIA: Prospective trials in patients with type 2 diabetes that lasted longer than one month were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Observational cohort studies of metformin treatment lasting greater than one month were also included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials to be included, assessed study quality and extracted data. The incidence of fatal and nonfatal Lactic Acidosis was recorded as cases per patient-years, for metformin treatment and for placebo or other treatments. The upper limit for the true incidence of cases in the metformin and non-metformin groups were calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed effects model for continuous data. MAIN RESULTS: Pooled data from 176 comparative trials and cohort studies revealed no cases of fatal or nonfatal Lactic Acidosis in 35,619 patient-years of metformin use or in 30,002 patients-years in the non-metformin group. Using Poisson statistics with 95% confidence intervals the upper limit for the true incidence of metformin-associated Lactic Acidosis was 8.4 cases per 100,000 patient-years, and the upper limit for the true incidence of Lactic Acidosis in the non-metformin group was 9 cases per 100,000 patient-years. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to placebo or other non-biguanide therapies. The mean lactate levels were slightly lower for metformin treatment compared to phenformin (WMD -0.75 mmol/L, 95% CI -0.86 to -0.15). REVIEWER'S CONCLUSIONS: There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of Lactic Acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments if prescribed under the study conditions, taking into account contra-indications.
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risk of fatal and nonfatal Lactic Acidosis with metformin use in type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2010Co-Authors: Shelley R Salpeter, Elizabeth Greyber, Gary A Pasternak, Edwin E. SalpeterAbstract:Background Metformin is an oral anti-hyperglycemic agent that has been shown to reduce total mortality compared to other anti-hyperglycemic agents, in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of Lactic Acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with Lactic Acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. Objectives To assess the incidence of fatal and nonfatal Lactic Acidosis, and to evaluate blood lactate levels, for those on metformin treatment compared to placebo or non-metformin therapies. Search strategy A comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Selection criteria Prospective trials and observational cohort studies in patients with type 2 diabetes of least one month duration were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Data collection and analysis The incidence of fatal and nonfatal Lactic Acidosis was recorded as cases per patient-years, for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed-effect model for continuous data. Main results Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal Lactic Acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group. Using Poisson statistics the upper limit for the true incidence of Lactic Acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies. Authors' conclusions There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of Lactic Acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments.
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risk of fatal and nonfatal Lactic Acidosis with metformin use in type 2 diabetes mellitus systematic review and meta analysis
JAMA Internal Medicine, 2003Co-Authors: Shelley R Salpeter, Elizabeth Greyber, Gary A Pasternak, Edwin E. SalpeterAbstract:Background: Metformin therapy for type 2 diabetes mellitus has been shown to reduce total mortality rates compared with other antihyperglycemic treatments but is thought to increase the risk of Lactic Acidosis. The true incidence of fatal and nonfatal Lactic Acidosis associated with metformin use is not known. Methods: A comprehensive search was performed to identify all comparative trials or observational cohort studies published between January 1, 1959, and March 31, 2002, that evaluated metformin therapy, alone or in combination with other treatments, for at least 1 month. The incidence of fatal and nonfatal Lactic Acidosis was recorded as cases per patient-years for metformin treatment and for placebo or other treatments. In a second analysis, lactate levels were measured as a net change from baseline or as mean treatment values for metformin and comparison groups. Results: Pooled data from 194 studies revealed no cases of fatal or nonfatal Lactic Acidosis in 36893 patient-years in the metformin group or in 30109 patients-years in the nonmetformin group. Using Poisson statistics with 95% confidence intervals, the probable upper limit for the true incidence of Lactic Acidosis in the metformin and nonmetformin groups was 8.1 and 9.9 cases per 100000 patient-years, respectively. There was no difference in lactate levels for metformin compared with placebo or other nonbiguanide therapies. Conclusion: There is no evidence to date that metformin therapy is associated with an increased risk of Lactic Acidosis or with increased levels of lactate compared with other antihyperglycemic treatments if the drugs are prescribed under study conditions, taking into account contraindications.
Shelley R Salpeter - One of the best experts on this subject based on the ideXlab platform.
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risk of fatal and nonfatal Lactic Acidosis with metformin use in type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2010Co-Authors: Shelley R Salpeter, Elizabeth Greyber, Gary A Pasternak, Edwin E. SalpeterAbstract:BACKGROUND: Metformin is an oral anti-hyperglycemic agent used in the treatment of type 2 diabetes mellitus. The results of the UK Prospective Diabetes Study indicate that metformin treatment is associated with a reduction in total mortality compared to other anti-hyperglycemic treatments. Metformin, however, is thought to increase the risk of Lactic Acidosis, and is considered to be contraindicated in many chronic hypoxemic conditions that may be associated with Lactic Acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. OBJECTIVES: To assess the incidence of fatal and nonfatal Lactic Acidosis with metformin use compared to placebo and other glucose-lowering treatments in patients with type 2 diabetes mellitus. A secondary objective was to evaluate the blood lactate levels for those on metformin treatment compared to placebo or non-metformin therapies. SEARCH STRATEGY: A search was performed of the Cochrane Controlled Trials Register and the Database of Abstracts of Reviews of Effectiveness (up to 4/2000), Medline (up to 11/2000), Embase (up to 11/2000), Oldmedline, and Reactions (up to 5/2000), in order to identify all studies of metformin treatment from 1966 to November 2000. The Cumulated Index Medicus was used to search relevant articles from 1959 to 1965. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Date of latest search: November 2000. SELECTION CRITERIA: Prospective trials in patients with type 2 diabetes that lasted longer than one month were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Observational cohort studies of metformin treatment lasting greater than one month were also included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials to be included, assessed study quality and extracted data. The incidence of fatal and nonfatal Lactic Acidosis was recorded as cases per patient-years, for metformin treatment and for placebo or other treatments. The upper limit for the true incidence of cases in the metformin and non-metformin groups were calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed effects model for continuous data. MAIN RESULTS: Pooled data from 176 comparative trials and cohort studies revealed no cases of fatal or nonfatal Lactic Acidosis in 35,619 patient-years of metformin use or in 30,002 patients-years in the non-metformin group. Using Poisson statistics with 95% confidence intervals the upper limit for the true incidence of metformin-associated Lactic Acidosis was 8.4 cases per 100,000 patient-years, and the upper limit for the true incidence of Lactic Acidosis in the non-metformin group was 9 cases per 100,000 patient-years. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to placebo or other non-biguanide therapies. The mean lactate levels were slightly lower for metformin treatment compared to phenformin (WMD -0.75 mmol/L, 95% CI -0.86 to -0.15). REVIEWER'S CONCLUSIONS: There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of Lactic Acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments if prescribed under the study conditions, taking into account contra-indications.
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risk of fatal and nonfatal Lactic Acidosis with metformin use in type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2010Co-Authors: Shelley R Salpeter, Elizabeth Greyber, Gary A Pasternak, Edwin E. SalpeterAbstract:Background Metformin is an oral anti-hyperglycemic agent that has been shown to reduce total mortality compared to other anti-hyperglycemic agents, in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of Lactic Acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with Lactic Acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. Objectives To assess the incidence of fatal and nonfatal Lactic Acidosis, and to evaluate blood lactate levels, for those on metformin treatment compared to placebo or non-metformin therapies. Search strategy A comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Selection criteria Prospective trials and observational cohort studies in patients with type 2 diabetes of least one month duration were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Data collection and analysis The incidence of fatal and nonfatal Lactic Acidosis was recorded as cases per patient-years, for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed-effect model for continuous data. Main results Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal Lactic Acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group. Using Poisson statistics the upper limit for the true incidence of Lactic Acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies. Authors' conclusions There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of Lactic Acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments.
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risk of fatal and nonfatal Lactic Acidosis with metformin use in type 2 diabetes mellitus systematic review and meta analysis
JAMA Internal Medicine, 2003Co-Authors: Shelley R Salpeter, Elizabeth Greyber, Gary A Pasternak, Edwin E. SalpeterAbstract:Background: Metformin therapy for type 2 diabetes mellitus has been shown to reduce total mortality rates compared with other antihyperglycemic treatments but is thought to increase the risk of Lactic Acidosis. The true incidence of fatal and nonfatal Lactic Acidosis associated with metformin use is not known. Methods: A comprehensive search was performed to identify all comparative trials or observational cohort studies published between January 1, 1959, and March 31, 2002, that evaluated metformin therapy, alone or in combination with other treatments, for at least 1 month. The incidence of fatal and nonfatal Lactic Acidosis was recorded as cases per patient-years for metformin treatment and for placebo or other treatments. In a second analysis, lactate levels were measured as a net change from baseline or as mean treatment values for metformin and comparison groups. Results: Pooled data from 194 studies revealed no cases of fatal or nonfatal Lactic Acidosis in 36893 patient-years in the metformin group or in 30109 patients-years in the nonmetformin group. Using Poisson statistics with 95% confidence intervals, the probable upper limit for the true incidence of Lactic Acidosis in the metformin and nonmetformin groups was 8.1 and 9.9 cases per 100000 patient-years, respectively. There was no difference in lactate levels for metformin compared with placebo or other nonbiguanide therapies. Conclusion: There is no evidence to date that metformin therapy is associated with an increased risk of Lactic Acidosis or with increased levels of lactate compared with other antihyperglycemic treatments if the drugs are prescribed under study conditions, taking into account contraindications.
