Alimentary Pharmacology & Therapeutics, Mar 31, 2007
SUMMARYThe design of randomized controlled trials to assess the efficacy of pharmacological measu... more SUMMARYThe design of randomized controlled trials to assess the efficacy of pharmacological measures for the prevention of the gastrointestinal side‐effects of anti‐inflammatory drugs requires an accurate estimate of excess risk under controlled conditions. Photocopies of 952 randomized controlled trial publications were obtained after scanning titles and abstracts of a MEDLINE computer search, 427 were excluded for obvious reasons, and 525 were again photocopied after obliterating source and results. Selection criteria were: the presence of a non‐anti‐inflammatory drug control group; at least 4 days of therapy; at least 3 days without anti‐inflammatory drugs before randomization; no complicating background drugs; mention of side‐effects; and a clear differentiation of gastrointestinal complications. Observer error, with two independent readings, for inclusion suitability in the study was 19% for Methods and 9% for Results. For the 44 aspirin trials, the mean therapy duration was 357 days; the unweighted rate difference between therapy and control groups (± 1 S.E.M.) for ulcer was 0.006 ± 0.003, for gross haemorrhage 0.006 ± 0.002 and for unspecified gastric symptoms 0.03 ± 0.01. In 123 non‐aspirin non‐steroidal anti‐inflammatory drug (NA—NSAID) trials, the mean duration was 67 days; the unweighted rate difference for ulcer was 0.0005 ± 0.0003, for gross haemorrhage 0.007 ± 0.004 and for unspecified gastric symptoms 0.02 ± 0.005. Risk differences were also pooled using the DerSimonian and Laird method, which weights studies inversely according to variance. Using this method, only the unspecified gastric symptoms for non‐aspirin non‐steroidal anti‐inflammatory drugs (NA—NSAIDs) and the haemorrhage for aspirin were found to be statistically significant. Longer studies have higher risk differences. Randomized control trials to determine prophylactic efficacy against haemorrhage (that is, to demonstrate a reduction of ulcer rate in the therapy group to the rate of controls) would require 190 patients in each group for NA—NSAIDs in studies of 2–6 months; 950 subjects would be needed to detect a 50% reduction. Randomized control trials to determine a reduction in ulcer rate to that of controls in patients on aspirin for more than 6 months would require 700 subjects in each group; 3346 subjects would be needed to detect a 50% reduction. Such studies are feasible.
American Journal of Industrial Medicine, Oct 17, 2011
Response to Dr. Reich's letter:'Sarcoid-like&a... more Response to Dr. Reich's letter:'Sarcoid-like'granulomatous pulmonary disease in world trade center disaster responders: Influence of incidence computation methodology in inferring airborne dust causation-Crowley-2011-American Journal of Industrial Medicine-...
Journal of acquired immune deficiency syndromes and human retrovirology, Apr 1, 1997
Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepith... more Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women. HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. Compared with HIV-negative women, HIV-positive women with a CD4+ cell count of less than 200/mm3 were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32-14.04), followed by women with a CD4+ count greater than 200/mm3 and an HIV RNA load greater than 20,000 copies/mL (OR = 5.78; 95% CI = 4.17-8.08) and women with a CD4+ count greater than 200/mm3 and an HIV RNA load less than 20,000 copies/mL (OR = 3.12; 95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64; 95% CI = 1.19-2.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20-1.99), and younger age (age < 30 years versus > or = 40 years; OR = 1.75; 95% CI = 1.23-2.49). Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well.
In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safe... more In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safety were assessed in 41 patients treated with dosages of 0.5-12.0 mg/kg/day. Among evaluable patients, 10% increases in CD4 lymphocyte counts were sustained in 24 (60%) of 40 during treatment; an NAUC response (normalized area under the CD4 cell count-versus-time curve > 1.0) was observed in 31 (91%) of 34 at 10 weeks and in 20 (80%) of 25 at 24 weeks; 15 (83%) of 18 had decreases in p24 antigenemia; and 24 (60%) of 40 gained > or = 2.5 kg body weight. Median CD4 lymphocyte levels remained above baseline for 6 months in patients receiving > 0.5 mg/kg/day. Median serum p24 antigen levels remained below baseline for > or = 1 year in patients with p24 antigen responses. The principal toxicity was peripheral neuropathy, which generally resolved after drug discontinuation but limited the dosage to < or = 2.0 mg/kg/day. Additional trials assessing the effect of stavudine on overall morbidity and mortality are ongoing.
Questions Does vitamin D supplementation reduce risk for acute respiratory tract infection (ARTI)... more Questions Does vitamin D supplementation reduce risk for acute respiratory tract infection (ARTI)? Do effects differ in participant subgroups? Review scope Included studies compared oral vitamin D3 supplementation with placebo, had research ethics approval, and prospectively collected data on ARTIs as a prespecified efficacy outcome. Long-term follow-up reports of primary randomized controlled trials (RCTs) were excluded. Primary outcome was ARTI. Other outcomes included upper ARTI, lower ARTI, ARTI-related hospitalization or emergency department visit, mortality, serious adverse events, and vitamin Drelated adverse reactions (hypercalcemia or renal stones). PROSPERO International Prospective Register of Systematic Reviews CRD42014013953. Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and ISRCTN registry, all to Dec 2015; and reference lists were searched for double-blind RCTs. 25 RCTs (n =11321, duration 7 wk to 1.5 y, [n =10933 with primary outcome data; 50% women; age 1 y 51%, 1.1 to <16 y 10%, 16 y 39%]) met the inclusion criteria. Individual patient data were obtained for all RCTs. 12 RCTs administered vitamin D3 in daily doses (7.5 to 100 g), 3 in weekly doses (35 to 500 g), 7 as bolus doses (0.75 to 5.0 mg) given once or every 1 to 3 months, and 3 used both daily (10 to 100 g) and bolus (2.4 to 2.5 mg) doses. All RCTs had adequate allocation concealment and blinded participants, study personnel, and outcome assessors; 23 RCTs had adequate follow-up rates. Main results The main results of 1-step individual patient data meta-analysis are in the Table. In prespecified subgroup analyses, effect of vitamin D supplementation for ARTIs differed by baseline serum 25-hydroxyvitamin D level (<25 nmol/L, 41% receiving vitamin D3 had ARTI vs 55% receiving placebo, P =0.002; 25 nmol/L, 59% vs 63%, P =0.15; P interaction =0.01) and dosing regimen (bolus dose 30000 IU, 36.4% vs 35.7%, P =0.67; no bolus dose, 45% vs 50%, P <0.001; P interaction =0.05) but not by age, body mass index, daily dose equivalents, asthma or chronic obstructive pulmonary disease status, or influenza vaccination status. Conclusion In children and adults, vitamin D3 supplementation reduces risk for acute respiratory tract infection. Oral vitamin D3 supplementation vs placebo* Outcomes Number of trials (n) Weighted event rates RRR (95% CI) NNT (CI) Vitamin D3 Placebo Any ARTI 25 (10933) 39% 42% 7.3% (2 to 12) 33 (20 to 101) Upper ARTI 19 (7019) 49% 50% 3.6% (1 to 9) NS Lower ARTI 9 (6698) 15.9% 16.5% 3.4% (8 to 15) NS ARTI-related hospitalization or emergency department visit 11 (7872) 1.0% 1.2% 17% (27 to 46) NS Serious adverse event 25 (11224) 3.9% 4.0% 1.9% (19 to 19) NS Renal stones 14 (3841) 0.09% 0.23% 60% (86 to 91) NS RRI (CI) NNH All-cause mortality 25 (11224) 1.2% 0.9% 39% (15 to 124) NS Hypercalcemia 14 (3850) 0.57% 0.52% 9.8% (52 to 154) NS *ARTI = acute respiratory tract infection; other abbreviations defined in Glossary. Unless stated otherwise, weighted event rates, RRR, RRI, NNT and CI calculated from placebo event rate and adjusted odds ratio for 1-step individual patient data meta-analysis in article using a random-effects model. Adjusted for age, sex, and study duration. Weighted event rates, RRR, RRI, and CI calculated from vitamin D3 and placebo group event rates. Commentary For almost 100 years we have known that vitamin D can prevent bone disease. Its use in other circumstances is controversial. 2 respected groups concluded that convincing evidence does not exist for benefits of screening asymptomatic adults or for prescribing supplements to prevent other diseases (1, 2). After reviewing much of the same evidence, the Endocrine Society recommended screening for, and treating, vitamin D deficiency in a sizable proportion of the population (3). The disagreements may be due to differing interpretations of existing data and their quality. The meta-analysis by Martineau and colleagues helps to clarify 1 narrow question and has several strengths. It combined individual patient data from 25 high-quality RCTs and so was able to look at effects in important subgroups. Although most participants were infants and children, the effect was consistent across all age groups and greatest in those with the lowest baseline levels of 25-hydroxyvitamin D, lending biological credibility to the findings. Adverse event rates were low and similar in treated and placebo groups. Martineau and colleagues suggested that unpublished studies were unlikely to change their results. However, time frames for follow-up and definitions of ARTI varied across RCTs, and treatment effects were small. Several large, long-term RCTs evaluating the effect of vitamin D supplementation for other outcomes are ongoing (4); some results may become available soon and could prompt updates (and perhaps better agreement) of guidelines. In the meantime, because the benefit of vitamin D…
... Acknowledgements We wish to acknowledge the contribution of Elyse Shapiro, RN and Robin Drehe... more ... Acknowledgements We wish to acknowledge the contribution of Elyse Shapiro, RN and Robin Dreher, RN, in facilitating the pharmacokinetic studies. Page 5. Meztodllta to rtepatobfliaiy dysfunction 713 References Bergan, T. (1978). ...
SOURCE CITATION Heath PT, Galiza EP, Baxter DN, et al. Safety and efficacy of NVX-CoV2373 Covid-1... more SOURCE CITATION Heath PT, Galiza EP, Baxter DN, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med. 2021;385:1172-83. 34192426.
A culture-proved case of Rocky Mountain spotted fever is described in which the typical findings ... more A culture-proved case of Rocky Mountain spotted fever is described in which the typical findings of the adult respiratory distress syndrome developed. Rocky Mountain spotted fever should be added to the list of conditions associated with the adult respiratory distress syndrome. This case also illustrates the difficulties in distinguishing Rocky Mountain spotted fever from atypical measles.
To analyze the policies of isoniazid prophylaxis for human immunodeficiency virus (HIV)-infected ... more To analyze the policies of isoniazid prophylaxis for human immunodeficiency virus (HIV)-infected tuberculin reactors and for HIV-infected anergic patients with unknown tuberculin status. Transition-state model of clinical immune deterioration of HIV-infection over ten years, review of published data, and a survey of AIDS experts. Outcome measures are the numbers of tuberculosis cases and deaths prevented and isoniazid toxicity cases and deaths occurring with prophylaxis. Hypothetical cohorts of HIV-infected 40-year-olds. Because the tuberculosis activation rate is so high in HIV-infected patients, the benefits of prophylaxis far outweigh the risks of isoniazid toxicity for tuberculin reactors with HIV infection at any stage of immune function: 1,469-2,868 tuberculosis cases and 170-274 deaths are prevented per 10,000 cohort over ten years, depending upon the cohort&#39;s initial immune state. The benefits of prophylaxis outweigh the risks of isoniazid toxicity for anergic HIV-infected patients if they come from a community with a 2% to 3% or greater prevalence of Mycobacterium tuberculosis infection. Isoniazid prophylaxis is a reasonable prevention measure for HIV-infected tuberculin reactors and for many HIV-infected anergic patients.
Loss of patients from clinical trials can nullify adequate randomization if the loss is unequally... more Loss of patients from clinical trials can nullify adequate randomization if the loss is unequally distributed among treatment groups. This study was designed to assess the magnitude of the problem in randomized control trials evaluating long-term therapy for survivors of myocardial infarction (MI). Only 19 of 52 trials reported having an explicit policy on withdrawals in the design stage; only 2 reported blinding the decision for withdrawal and only 7 reported accounting for withdrawals in sizing. In addition, only 16 gave the reader enough information to calculate the effect of withdrawals on trial results. In 2 of these 16 trials a p less than 0.05 result obtained by including withdrawals (intention to treat method) was reduced to p less than 0.05 when withdrawals were excluded. It is evident that many long-term trials do not contain adequate data on withdrawals. Readers of published trials are seldom able to judge whether or not withdrawals might affect the final results.
Alimentary Pharmacology & Therapeutics, Mar 31, 2007
SUMMARYThe design of randomized controlled trials to assess the efficacy of pharmacological measu... more SUMMARYThe design of randomized controlled trials to assess the efficacy of pharmacological measures for the prevention of the gastrointestinal side‐effects of anti‐inflammatory drugs requires an accurate estimate of excess risk under controlled conditions. Photocopies of 952 randomized controlled trial publications were obtained after scanning titles and abstracts of a MEDLINE computer search, 427 were excluded for obvious reasons, and 525 were again photocopied after obliterating source and results. Selection criteria were: the presence of a non‐anti‐inflammatory drug control group; at least 4 days of therapy; at least 3 days without anti‐inflammatory drugs before randomization; no complicating background drugs; mention of side‐effects; and a clear differentiation of gastrointestinal complications. Observer error, with two independent readings, for inclusion suitability in the study was 19% for Methods and 9% for Results. For the 44 aspirin trials, the mean therapy duration was 357 days; the unweighted rate difference between therapy and control groups (± 1 S.E.M.) for ulcer was 0.006 ± 0.003, for gross haemorrhage 0.006 ± 0.002 and for unspecified gastric symptoms 0.03 ± 0.01. In 123 non‐aspirin non‐steroidal anti‐inflammatory drug (NA—NSAID) trials, the mean duration was 67 days; the unweighted rate difference for ulcer was 0.0005 ± 0.0003, for gross haemorrhage 0.007 ± 0.004 and for unspecified gastric symptoms 0.02 ± 0.005. Risk differences were also pooled using the DerSimonian and Laird method, which weights studies inversely according to variance. Using this method, only the unspecified gastric symptoms for non‐aspirin non‐steroidal anti‐inflammatory drugs (NA—NSAIDs) and the haemorrhage for aspirin were found to be statistically significant. Longer studies have higher risk differences. Randomized control trials to determine prophylactic efficacy against haemorrhage (that is, to demonstrate a reduction of ulcer rate in the therapy group to the rate of controls) would require 190 patients in each group for NA—NSAIDs in studies of 2–6 months; 950 subjects would be needed to detect a 50% reduction. Randomized control trials to determine a reduction in ulcer rate to that of controls in patients on aspirin for more than 6 months would require 700 subjects in each group; 3346 subjects would be needed to detect a 50% reduction. Such studies are feasible.
American Journal of Industrial Medicine, Oct 17, 2011
Response to Dr. Reich&amp;amp;amp;#x27;s letter:&amp;amp;amp;#x27;Sarcoid-like&amp;a... more Response to Dr. Reich&amp;amp;amp;#x27;s letter:&amp;amp;amp;#x27;Sarcoid-like&amp;amp;amp;#x27;granulomatous pulmonary disease in world trade center disaster responders: Influence of incidence computation methodology in inferring airborne dust causation-Crowley-2011-American Journal of Industrial Medicine-...
Journal of acquired immune deficiency syndromes and human retrovirology, Apr 1, 1997
Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepith... more Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women&#39;s Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women. HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. Compared with HIV-negative women, HIV-positive women with a CD4+ cell count of less than 200/mm3 were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32-14.04), followed by women with a CD4+ count greater than 200/mm3 and an HIV RNA load greater than 20,000 copies/mL (OR = 5.78; 95% CI = 4.17-8.08) and women with a CD4+ count greater than 200/mm3 and an HIV RNA load less than 20,000 copies/mL (OR = 3.12; 95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64; 95% CI = 1.19-2.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20-1.99), and younger age (age &lt; 30 years versus &gt; or = 40 years; OR = 1.75; 95% CI = 1.23-2.49). Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well.
In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safe... more In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safety were assessed in 41 patients treated with dosages of 0.5-12.0 mg/kg/day. Among evaluable patients, 10% increases in CD4 lymphocyte counts were sustained in 24 (60%) of 40 during treatment; an NAUC response (normalized area under the CD4 cell count-versus-time curve &gt; 1.0) was observed in 31 (91%) of 34 at 10 weeks and in 20 (80%) of 25 at 24 weeks; 15 (83%) of 18 had decreases in p24 antigenemia; and 24 (60%) of 40 gained &gt; or = 2.5 kg body weight. Median CD4 lymphocyte levels remained above baseline for 6 months in patients receiving &gt; 0.5 mg/kg/day. Median serum p24 antigen levels remained below baseline for &gt; or = 1 year in patients with p24 antigen responses. The principal toxicity was peripheral neuropathy, which generally resolved after drug discontinuation but limited the dosage to &lt; or = 2.0 mg/kg/day. Additional trials assessing the effect of stavudine on overall morbidity and mortality are ongoing.
Questions Does vitamin D supplementation reduce risk for acute respiratory tract infection (ARTI)... more Questions Does vitamin D supplementation reduce risk for acute respiratory tract infection (ARTI)? Do effects differ in participant subgroups? Review scope Included studies compared oral vitamin D3 supplementation with placebo, had research ethics approval, and prospectively collected data on ARTIs as a prespecified efficacy outcome. Long-term follow-up reports of primary randomized controlled trials (RCTs) were excluded. Primary outcome was ARTI. Other outcomes included upper ARTI, lower ARTI, ARTI-related hospitalization or emergency department visit, mortality, serious adverse events, and vitamin Drelated adverse reactions (hypercalcemia or renal stones). PROSPERO International Prospective Register of Systematic Reviews CRD42014013953. Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and ISRCTN registry, all to Dec 2015; and reference lists were searched for double-blind RCTs. 25 RCTs (n =11321, duration 7 wk to 1.5 y, [n =10933 with primary outcome data; 50% women; age 1 y 51%, 1.1 to <16 y 10%, 16 y 39%]) met the inclusion criteria. Individual patient data were obtained for all RCTs. 12 RCTs administered vitamin D3 in daily doses (7.5 to 100 g), 3 in weekly doses (35 to 500 g), 7 as bolus doses (0.75 to 5.0 mg) given once or every 1 to 3 months, and 3 used both daily (10 to 100 g) and bolus (2.4 to 2.5 mg) doses. All RCTs had adequate allocation concealment and blinded participants, study personnel, and outcome assessors; 23 RCTs had adequate follow-up rates. Main results The main results of 1-step individual patient data meta-analysis are in the Table. In prespecified subgroup analyses, effect of vitamin D supplementation for ARTIs differed by baseline serum 25-hydroxyvitamin D level (<25 nmol/L, 41% receiving vitamin D3 had ARTI vs 55% receiving placebo, P =0.002; 25 nmol/L, 59% vs 63%, P =0.15; P interaction =0.01) and dosing regimen (bolus dose 30000 IU, 36.4% vs 35.7%, P =0.67; no bolus dose, 45% vs 50%, P <0.001; P interaction =0.05) but not by age, body mass index, daily dose equivalents, asthma or chronic obstructive pulmonary disease status, or influenza vaccination status. Conclusion In children and adults, vitamin D3 supplementation reduces risk for acute respiratory tract infection. Oral vitamin D3 supplementation vs placebo* Outcomes Number of trials (n) Weighted event rates RRR (95% CI) NNT (CI) Vitamin D3 Placebo Any ARTI 25 (10933) 39% 42% 7.3% (2 to 12) 33 (20 to 101) Upper ARTI 19 (7019) 49% 50% 3.6% (1 to 9) NS Lower ARTI 9 (6698) 15.9% 16.5% 3.4% (8 to 15) NS ARTI-related hospitalization or emergency department visit 11 (7872) 1.0% 1.2% 17% (27 to 46) NS Serious adverse event 25 (11224) 3.9% 4.0% 1.9% (19 to 19) NS Renal stones 14 (3841) 0.09% 0.23% 60% (86 to 91) NS RRI (CI) NNH All-cause mortality 25 (11224) 1.2% 0.9% 39% (15 to 124) NS Hypercalcemia 14 (3850) 0.57% 0.52% 9.8% (52 to 154) NS *ARTI = acute respiratory tract infection; other abbreviations defined in Glossary. Unless stated otherwise, weighted event rates, RRR, RRI, NNT and CI calculated from placebo event rate and adjusted odds ratio for 1-step individual patient data meta-analysis in article using a random-effects model. Adjusted for age, sex, and study duration. Weighted event rates, RRR, RRI, and CI calculated from vitamin D3 and placebo group event rates. Commentary For almost 100 years we have known that vitamin D can prevent bone disease. Its use in other circumstances is controversial. 2 respected groups concluded that convincing evidence does not exist for benefits of screening asymptomatic adults or for prescribing supplements to prevent other diseases (1, 2). After reviewing much of the same evidence, the Endocrine Society recommended screening for, and treating, vitamin D deficiency in a sizable proportion of the population (3). The disagreements may be due to differing interpretations of existing data and their quality. The meta-analysis by Martineau and colleagues helps to clarify 1 narrow question and has several strengths. It combined individual patient data from 25 high-quality RCTs and so was able to look at effects in important subgroups. Although most participants were infants and children, the effect was consistent across all age groups and greatest in those with the lowest baseline levels of 25-hydroxyvitamin D, lending biological credibility to the findings. Adverse event rates were low and similar in treated and placebo groups. Martineau and colleagues suggested that unpublished studies were unlikely to change their results. However, time frames for follow-up and definitions of ARTI varied across RCTs, and treatment effects were small. Several large, long-term RCTs evaluating the effect of vitamin D supplementation for other outcomes are ongoing (4); some results may become available soon and could prompt updates (and perhaps better agreement) of guidelines. In the meantime, because the benefit of vitamin D…
... Acknowledgements We wish to acknowledge the contribution of Elyse Shapiro, RN and Robin Drehe... more ... Acknowledgements We wish to acknowledge the contribution of Elyse Shapiro, RN and Robin Dreher, RN, in facilitating the pharmacokinetic studies. Page 5. Meztodllta to rtepatobfliaiy dysfunction 713 References Bergan, T. (1978). ...
SOURCE CITATION Heath PT, Galiza EP, Baxter DN, et al. Safety and efficacy of NVX-CoV2373 Covid-1... more SOURCE CITATION Heath PT, Galiza EP, Baxter DN, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med. 2021;385:1172-83. 34192426.
A culture-proved case of Rocky Mountain spotted fever is described in which the typical findings ... more A culture-proved case of Rocky Mountain spotted fever is described in which the typical findings of the adult respiratory distress syndrome developed. Rocky Mountain spotted fever should be added to the list of conditions associated with the adult respiratory distress syndrome. This case also illustrates the difficulties in distinguishing Rocky Mountain spotted fever from atypical measles.
To analyze the policies of isoniazid prophylaxis for human immunodeficiency virus (HIV)-infected ... more To analyze the policies of isoniazid prophylaxis for human immunodeficiency virus (HIV)-infected tuberculin reactors and for HIV-infected anergic patients with unknown tuberculin status. Transition-state model of clinical immune deterioration of HIV-infection over ten years, review of published data, and a survey of AIDS experts. Outcome measures are the numbers of tuberculosis cases and deaths prevented and isoniazid toxicity cases and deaths occurring with prophylaxis. Hypothetical cohorts of HIV-infected 40-year-olds. Because the tuberculosis activation rate is so high in HIV-infected patients, the benefits of prophylaxis far outweigh the risks of isoniazid toxicity for tuberculin reactors with HIV infection at any stage of immune function: 1,469-2,868 tuberculosis cases and 170-274 deaths are prevented per 10,000 cohort over ten years, depending upon the cohort&#39;s initial immune state. The benefits of prophylaxis outweigh the risks of isoniazid toxicity for anergic HIV-infected patients if they come from a community with a 2% to 3% or greater prevalence of Mycobacterium tuberculosis infection. Isoniazid prophylaxis is a reasonable prevention measure for HIV-infected tuberculin reactors and for many HIV-infected anergic patients.
Loss of patients from clinical trials can nullify adequate randomization if the loss is unequally... more Loss of patients from clinical trials can nullify adequate randomization if the loss is unequally distributed among treatment groups. This study was designed to assess the magnitude of the problem in randomized control trials evaluating long-term therapy for survivors of myocardial infarction (MI). Only 19 of 52 trials reported having an explicit policy on withdrawals in the design stage; only 2 reported blinding the decision for withdrawal and only 7 reported accounting for withdrawals in sizing. In addition, only 16 gave the reader enough information to calculate the effect of withdrawals on trial results. In 2 of these 16 trials a p less than 0.05 result obtained by including withdrawals (intention to treat method) was reduced to p less than 0.05 when withdrawals were excluded. It is evident that many long-term trials do not contain adequate data on withdrawals. Readers of published trials are seldom able to judge whether or not withdrawals might affect the final results.
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Papers by Henry Sacks