James Freston - Academia.edu (original) (raw)

Papers by James Freston

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2011

Background & Aims-Fluoroquinolone-induced liver injury is rare; no prospective studies of well-ch... more Background & Aims-Fluoroquinolone-induced liver injury is rare; no prospective studies of well-characterized case series have been published. We studied patients with fluoroquinoloneinduced hepatoxicity, using data from the Drug-Induced Liver Injury Network (DILIN) to characterize injury patterns, outcomes, and associated features. Methods-We identified subjects with fluoroquinolone hepatotoxicity who enrolled in the DILIN from September 2004 to January 2010. Demographic, clinical, and laboratory data were analyzed by descriptive statistical methods. Results-Of the 679 registrants in the DILIN prospective study, 12 had hepatoxicity from fluoroquinolones (6 ciprofloxacin, 4 moxifloxacin, 1 levofloxacin, and 1 gatifloxacin). Seven were women; the median age was 57 years (range 23-80 years), and the median time from the start of fluoroquinolone therapy to symptoms was only 4 days (range 1-39 days). Nine cases developed symptoms on medication (2, 8, and 32 days after they stopped the medication, 3 patients each). Cases were equally distributed among hepatocellular injury (predominantly increased levels of alanine aminotransferase), cholestatic injury (predominantly increased levels of alkaline phosphatase [AP]), and both. Seven cases had immunoallergic features. Patients with mixed

BMC Cancer, 2021

Background There is limited real-world safety information on palbociclib for treatment of advance... more Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbocicl...

Journal of Autoimmunity, 2020

Hepatology, 2018

Treatment of hematological malignancy with antibody‐drug conjugates (ADCs) may cause liver injury... more Treatment of hematological malignancy with antibody‐drug conjugates (ADCs) may cause liver injury. ADCs deliver a toxic moiety into antigen‐expressing tumor cells, but may also injure hepatic sinusoids (sinusoidal obstruction syndrome; SOS). We studied patients who received an anti‐CD22/calicheamicin conjugate (inotuzumab ozogamicin; InO) to gain insight into mechanisms of sinusoidal injury, given that there are no CD22+ cells in the normal liver, but nonspecific uptake of ADCs by liver sinusoidal endothelial cells (LSECs). Six hundred thirty‐eight patients (307 with acute lymphocytic leukemia [ALL], 311 with non‐Hodgkin’s lymphoma [NHL]) were randomized to either InO or standard chemotherapy (controls). While blinded to treatment assignment, we reviewed all cases with hepatobiliary complications to adjudicate the causes. Frequency of SOS among patients who received InO was 5 of 328 (1.5%), compared to no cases among 310 control patients. Drug‐induced liver injury (DILI) developed i...

Canadian Journal of Gastroenterology, 2002

Proton pump inhibitor therapy is so successful at relieving refluxrelated symptoms and healing es... more Proton pump inhibitor therapy is so successful at relieving refluxrelated symptoms and healing esophageal erosions that it has supplanted formal diagnostic techniques, such as endoscopy and esophageal pH monitoring, for the initial management of gastroesophageal reflux disease. The response to antisecretory therapy is not indicative, however, of Barrett’s esophagus or esophageal adenocarcinoma. Patients with prolonged and severe reflux symptoms, especially if they are over the age of 60 years, are at risk of these complications. For them, endoscopy is the only appropriate investigation for detecting Barrett’s esophagus and dysplasia or cancer. Because of the difficulty in distinguishing dysplasia from inflammatory and regenerative changes, endoscopy should be undertaken while the patient is on effective antisecretory therapy. Endoscopy should be offered only to patients who are suitable for further therapy (especially esophagectomy), and only if they understand the implications of a...

American Journal of Gastroenterology, 2001

The Western journal of medicine, 1980

Adenomas and hamartomas, two genetically transmitted histologic types of gastrointestinal polypos... more Adenomas and hamartomas, two genetically transmitted histologic types of gastrointestinal polyposis, are associated in syndromes with extragastrointestinal manifestations. Adenomas that predispose to adenocarcinoma are basic to familial polyposis coli, the Gardner syndrome and the Turcot syndrome. Gastrointestinal polyps and extragastrointestinal lesions serve as a warning, providing time for diagnosis and treatment of adenomas to prevent their malignant transformation in patients and their relatives. Hamartomas with no malignancy potential, but having a tendency toward bleeding and bowel obstruction, are associated with the Peutz-Jeghers syndrome, juvenile polyposis, multiple hamartoma syndrome, basal-cell nevus syndrome and the Cronkhite-Canada syndrome. Most of these lesions and syndromes follow the inheritance pattern of a single autosomal dominant gene.

World Journal of Surgery, 2000

Most peptic ulcers are caused by Helicobacter pylori infection. The infection is best diagnosed b... more Most peptic ulcers are caused by Helicobacter pylori infection. The infection is best diagnosed by a radiolabeled carbon urea breath test, which also can prove that eradication therapy was successful. Serologic testing is useful for establishing prior or present infection but not to determine if the infection has been eradicated. Endoscopic tests usually are not needed to establish a diagnosis. Modern ulcer treatment consists of H. pylori eradication in infected patients. A combination of a proton pump inhibitor plus clarithromycin and amoxicillin or a proton pump inhibitor plus bismuth, metronidazole, and tetracycline are the most effective regimens. Reinfection is less than 2% per year in developed countries. Evidence suggests that H. pylori eradication may foster the development of erosive esophagitis, but confirmatory studies are needed. Studies also suggest an interaction between H. pylori infection and peptic ulcers related to the use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the studies are conflicting: One shows that H. pylori eradication protects against NSAID-related ulcers; another suggests protection afforded by the infection. Non-H. pylori peptic ulcers remain a challenge, especially in the United States, where one study showed that 42% of peptic ulcers were not due to the infection. Some non-H. pylori ulcers are refractory to usual doses of antisecretory drugs.

Scandinavian Journal of Gastroenterology, 1987

Expert Review of Clinical Pharmacology, 2013

Migraine is a common neurological syndrome that affects approximately 10-20% of the population. T... more Migraine is a common neurological syndrome that affects approximately 10-20% of the population. The pathophysiology of migraine is unclear. 5-hydroxytriptamine is a key mediator in the pathogenesis of migraine and thus 5-HT1-receptor agonists are the principal drugs for acute migraine therapy. There are three classes of drugs for migraine: over-the-counter analgesics and nonsteroidal anti-inflammatory drugs for acute mild migraine, specific prescription drugs (triptans and ergot alkaloids) for acute severe migraine and pharmacological agents for prophylaxis of migraine. Sumatriptan, naratriptan and others, referred to as &amp;amp;amp;#39;triptans&amp;amp;amp;#39;, are the mainstay for acute treatment of migraine. Ergot alkaloids (ergotamine, dihydroergotamine) are used in patients with frequent, moderate migraine, but are less effective than triptans. There are several agents for prevention of migraine occurrence in patients with frequent or severe disabling migraine attacks. New drugs with improved efficacy and reduced side effects are needed for effective treatment and prevention of migraine.

Drug Safety, 2010

Background: Challenges exist in the clinical diagnosis of drug-induced liver injury (DILI) and in... more Background: Challenges exist in the clinical diagnosis of drug-induced liver injury (DILI) and in obtaining information on hepatotoxicity in humans. Objective: (i) To develop a unified list that combines drugs incriminated in well vetted or adjudicated DILI cases from many recognized sources and drugs that have been subjected to serious regulatory actions due to hepatotoxicity; and (ii) to supplement the drug list with data on reporting frequencies of liver events in the WHO individual case safety report database (VigiBaseÔ). Data Sources and Extraction: (i) Drugs identified as causes of DILI at three major DILI registries; (ii) drugs identified as causes of drug-induced acute liver failure (ALF) in six different data sources, including major ALF registries and previously published ALF studies; and (iii) drugs identified as being subjected to serious governmental regulatory actions due to their hepatotoxicity in Europe or the US were collected. The reporting frequency of adverse events was determined using VigiBaseÔ, computed as Empirical Bayes Geometric Mean (EBGM) with 90% confidence interval for two

Drug Safety, 2009

Non-alcohQlic fatty liver disease (NAFLD), the major hqm!ic manifestation or type 2 diabetes mell... more Non-alcohQlic fatty liver disease (NAFLD), the major hqm!ic manifestation or type 2 diabetes mellitus, is the most t..:'OmnlOl1 liver disease in the US, Thhu:olidincdiollcs. a commonly used drug class ror the treatment or type ' 2 diabetes. have emerged us a potl~ntiHlly useful treatment 1'01' NAFLD. There arc. howl.'vl,.'r, lingering conccrns ,tboul thdr potential lox-icily as well as emerging. conc~rns abollt how \0 monitor for alltl aSSess hCPHlOt'oxicil)'. We COl1ll11Ctcd it fi.lndolllizcu. long-tc1111. dOllble~blil1d, hepatic safely~lUdy at 171 centres in the US in which 2097 patients with lYP~2 diabetes received either piog.litar.,onc or glibendamidc (glybllride), "fethod!': Pnticnts were ralldomil.cd to rcc-eive cither piogliHllonc (15-45 mg: onte daily) OJ' glibcnclan1idc (5-15mg once d.lHy) for J YC<lrs. The pJ'im<try objective WtH; to cvallmte drug.•induced liver injtll"y manifested by liver en-Iymc elevation::.. measured every 8 \\'ccks 1'01' the first year llnd every t 2 weeks thereafter. Tile pl'inmry enclpoinr was a t:ontir11lcd AL T greater th.tn three times the upper limit of normal (>JxULN) with lJ se.condary endpoint of gxUL:-':. .l\1nin rcsults: The intcnt-to-1fcu(population included 105\ pioglilazonctrcated anJ 1046 glibcndamidc-trcated patienls: of thesc~411 pioglital.onc paticnl:\ and 413 glibcnclamidc patients completed the study. The incidence of hcputocdlular injury \Vas 0 \vith pioglitazone and 4 (O.3X%) \\'ith glibcn-c1amidc (p ::;:0.0(17). Analyses of the secondary endpoints revealed no ALT >g x LlLN for pioglilal.One vcrs", I with glibcncl",nidc (1'=0.4988): no ALT >3 x lJLN + tOl.1l bilirubin 2 x ULN with pioglit.\zonc versus I \... •ith glibcnclamidc (p= 0.4988); and fewer ALT >.3 x ULN single elevations ,vith ploglilawnc (n =.1) thnn with gliocndHlllidc I,,=9: 1'= 0.(907). Signilicnnlly (1':0; 0.(5) !c\vcr case,s or ALT > 1.5 x ULN. asparratc anlinOlnlt.lslcrasc >1.5 x ULN and y~gll\tamyl transpcptidase >1.5 x ULN \Vcre seen with pioglitazollc compared with glibcnclml'1idc. No ca~C' or hepatic dysl'unction or hepatic failure was 'lht"UUlNfll. rcport~d in t'ithcr trciHtncnt group: two cases of hepatic cirrhosis with gHbcnd amidc were reponed. Conclusion: This study demonstrates an hepatic salety proJilc of' pioglilazonc similur to that ol'glibcnclamidc in long-lerm lise in patients with poorly controlled type 2. diabetes, Trial rcgisln\tion number {clillici;lltrinls.gov): NCTOO4943t2 Trial registration lltlmbcr (dinicaltrials.gov):~<. '"T00494J 11.

Digestive Diseases and Sciences, 1995

Digestive Diseases and Sciences, 2009