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By M. Norris. Barrington University.

Intraoperative hypothermia is an independent risk factor for early cytomegalovirus infection in liver transplant recipients isoniazid 300mg otc medicine 801. Leukocyte reduction during orthotopic liver trans- plantation and postoperative outcome: a pilot study cheap 300 mg isoniazid mastercard symptoms 2 months pregnant. Kidney failure associated with liver transplantation or liver failure: the impact of continuous veno-venous hemofiltration purchase isoniazid 300 mg with mastercard medicine abuse. Role of epicardial pacing wire cultures in the diagnosis of poststernotomy mediastinitis isoniazid 300mg with mastercard medications to treat bipolar disorder. A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation: results at three years. A prospective search for ocular lesions in hospitalized patients with significant bacteremia. Characteristics of discrepancies between clinical and autopsy diagnoses in the intensive care unit: a 5-year review. Staphylococcus aureus nasal colonization and association with infections in liver transplant recipients. The diagnosis of pneumonia in renal transplant recipients using invasive and noninvasive procedures. Legionellosis in a lung transplant recipient obscured by cytomegalovirus infection and Clostridium difficile colitis. Impact of bacterial and fungal donor organ contamination in lung, heart-lung, heart and liver transplantation. Infections caused by Legionella micdadei and Legionella pneumophila among renal transplant recipients. Isolation of Legionella pneumophila by centrifugation of shell vial cell cultures from multiple liver and lung abscesses. Use of terminal tap water filter systems for prevention of nosocomial legionellosis. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Rhodococcus equi infection in transplant recipients: case report and review of the literature. Successful medical treatment of multiple brain abscesses due to Nocardia farcinica in a paediatric renal transplant recipient. Challenges in the diagnosis and management of Nocardia infections in lung transplant recipients. Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. Risk factors of invasive aspergillosis after heart transplantation: protective role of oral itraconazole prophylaxis. Invasive fungal infections in liver transplant recipients receiving tacrolimus as the primary immunosuppressive agent. Environmental surveillance and other control measures in the prevention of nosocomial fungal infections. Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study. Treatment of solid organ transplant patients with invasive fungal infections: should a combination of antifungal drugs be used? Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi. Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome. Antifungal management practices and evolution of infection in organ transplant recipients with Cryptococcus neoformans infection. Allograft loss in renal transplant recipients with Cryptococcus neoformans associated immune reconstitution syndrome. Significance of the isolation of Candida species from respiratory samples in critically ill, non-neutropenic patients. Candida infection in a stent inserted for tracheal stenosis after heart lung transplantation. Candidal anastomotic infection in lung transplant recipients: successful treatment with a combination of systemic and inhaled antifungal agents. Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Management of herpes simplex virus type 1 pneumonia following liver transplantation. Acute adenoviral infection of a graft by serotype 35 following renal transplantation. Treatment of parainfluenza virus 3 pneumonia in a cardiac transplant recipient with intravenous ribavirin and methylprednisolone. Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Cell-mediated immune response to influenza vaccination in lung transplant recipients. Viral infections in immunocompromised patients: what’s new with respiratory viruses? Human metapneumovirus in lung transplant recipients and comparison to respiratory syncytial virus. Lower respiratory viral illnesses: improved diagnosis by molecular methods and clinical impact. Incidence and management of abdominal closure-related complications in adult intestinal transplantation. Effect of antibiotic prophylaxis on the risk of surgical site infection in orthotopic liver transplant. Surgical site infection in liver transplant recipients: impact of the type of perioperative prophylaxis. Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: endoscopic findings and results of therapy. Biliary tract complications following 52 consecutive orthotopic liver transplants. Preliminary study of choledochocholedochostomy without T tube in liver transplantation: a comparative study. Aspergillus mediastinitis following orthotopic heart trans- plantation: case report and review of the literature. Risk factors for early, cumulative, and fatal infections after heart transplantation: a multiinstitutional study. Management of urinary tract infections and lymphocele in renal transplant recipients. Complications of cyclosporine-prednisone immunosup- pression in 402 renal allograft recipients exclusively followed at a single center for from one to five years. Significance of pretransplant urinary tract infection in short- term renal allograft function and survival. Acute pyelonephritis represents a risk factor impairing long-term kidney graft function. Effect of time after transplantation on microbiology of urinary tract infections among renal transplant recipients. Urinary tract infection due to Corynebacterium urealyticum in kidney transplant recipients: an underdiagnosed etiology for obstructive uropathy and graft dysfunction-results of a prospective cohort study. Incidence of urinary tract infections caused by germs resistant to antibiotics commonly used after renal transplantation. Clinically “silent” weight loss associated with mycophenolate mofetil in pediatric renal transplant recipients. Prevalence of cytomegalovirus in the gastrointes- tinal tract of renal transplant recipients with persistent abdominal pain.

Therefore cheap 300 mg isoniazid with amex medicine to stop contractions, it is important to carefully calculate the sample size required prior to the study commencing and also consider the sample size when interpreting the results of the statistical tests purchase isoniazid 300mg overnight delivery medicine ads. This handbook should be available for anyone in the team to refer to at any time to facilitate considered data collection and data analysis practices buy 300mg isoniazid mastercard treatment narcissistic personality disorder. Suggested contents of data analysis log sheets that could be kept in the study handbook are shown in Box 1 generic 300 mg isoniazid fast delivery treatment variance. In this, it is important that data are treated carefully and analysed by people who are familiar with their content, their meaning and the interrelationship between variables. Before beginning any statistical analyses, a data analysis plan should be agreed upon in consultation with the study team. The plan can include the research questions or hypotheses that will be tested, the outcome and explanatory variables that will be used, the journal where the results will be published and/or the scientific meeting where the findings will be presented. A good way to handle data analyses is to create a log sheet for each proposed paper, abstract or report. The log sheets should be formal documents that are agreed to by all stakeholders and that are formally archived in the study handbook. When a research team is managed efficiently, a study handbook is maintained that has up-to-date docu- mentation of all details of the study protocol and the study processes. This is especially important when the data set will be accessed in the future by researchers who are not familiar with all aspects of data collection or the coding and recoding of the variables. Data management and documentation are relatively mundane processes compared to the excitement of statistical analyses but are essential. Laboratory researchers document every detail of their work as a matter of course by maintaining accurate laboratory books. All researchers undertaking clinical and epidemiological studies should be equally dili- gent and document all of the steps taken to reach their conclusions. Documentation can be easily achieved by maintaining a data management book with a log sheet for each data analysis. In this, all steps in the data management processes are recorded together with the information of names and contents of files, the coding and names of variables and the results of the statistical analyses. Many funding bodies and ethics committees require that all steps in data analyses are documented and that in addition to archiving the data, the data sheets, the output files and the participant records are kept for 5 years or up to 15 years after the results are published. Although it may be tempt- ing to jump straight into the analyses that will answer the study questions rather than spend time obtaining descriptive statistics, a working knowledge of the descriptive statis- tics often saves time by avoiding analyses having to be repeated for example because outliers, missing values or duplicates have not been addressed or groups with small numbers are not identified. When entering data, it is important to crosscheck the data file with the original records to ensure that data has been entered correctly. It is important to have a high standard of 14 Chapter 1 data quality in research databases at all times because good data management practice is a hallmark of scientific integrity. Describing the charac- teristics of the sample also allows other researchers to judge the generalizability of the results. This is preferable to using an implausible value such as 9 or 999 which was commonly used in the past. If these values are not accurately defined as discrete missing values in Missing column displayed in Variable View, they are easily incorporated into the analyses, thus producing erroneous results. Although these values can be predefined as system missing, this coding scheme is discouraged because it is inefficient, requires data analysts to be familiar with the coding scheme and has the potential for error. In the spreadsheet, the variable for ‘place of birth’ is coded as a string variable. If the variable had been defined as numeric, the missing values would have been omitted. When collecting data in any study, it is essential to have methods in place to pre- vent missing values in, say, at least 95% of the data set. Methods such as restructuring questionnaires in which participants decline to provide sensitive information or train- ing research staff to check that all fields are complete at the point of data collection are invaluable in this process. In large epidemiological and longitudinal data sets, some missing data may be unavoidable. However, in clinical trials, it may be unethical to col- lect insufficient information about some participants so that they have to be excluded from the final analyses. If the number of missing values is small and the missing values occur randomly throughout the data set, the cases with missing values can be omitted from the anal- yses. This is the default option in most statistical packages and the main effect of this process is to reduce statistical power, that is the ability to show a statistically significant difference between groups when a clinically important difference exists. Missing values that are scattered randomly throughout the data are less of a problem than non-random missing values that can affect both the power of the study and the generalizability of the results. For example, if people in higher income groups selectively decline to answer questions about income, the distribution of income in the population will not be known and analyses that include income will not be generalizable to people in higher income groups. When analysing data, it is important to determine whether data is missing completely at random, missing at random, or missing not at random. In other studies, a mean value (if the variable is normally distributed) or a median value (if the variable is non-normal dis- tributed) may be used to replace missing values. A summary of some of the commands that are widely used in routine data analyses are shown in Table 1. How to use the commands to select a subset of variables and recode variables is shown below. Also, the use of these commands is demonstrated in more detail in the following chapters. Sort cases Sorts the data set into ascending or descending order using one or more variables. Merge files Allows the merge of one or more data files using a variable common to both sets. Restructure Changes data sets from wide format (one line per subject) to long format (multiple lines per subject, for example, when there are multiple time points), and vice versa. Select cases By using conditional expressions, a subgroup of cases can be selected for analysis based on one or more variables. Transform menu Compute Creates a new variable based on transformation of existing variables or by using mathematical functions. Variables can be grouped into ‘bins’ or interval cut off points such as quantiles or tertiles. Date and time wizard Used to create a date/time variable, to add or subtract dates and times. The result is presented in a new variable in units of seconds and needs to be back converted to hours or days. Replace missing values Replaces missing values with an option to use various methods of imputation. A smaller subset of variables to be used in analyses can be selected as shown in Box 1. When using a subset, only the variables selected are displayed in the data analysis dialogue boxes. This can make analyses more efficient by avoiding having to search up and down a long list of variables for the ones required. Using a subset is espe- cially useful when working with a large data set and only a few variables are needed for a current analysis. Set_1 Highlight Variables required in the analyses and click them into Variables in Set Click on Add Set Click Close surgery. Using the Paste command for the above recode provides the following documentation. After recoding, the value labels for the three new categories of place2 that have been created can be added in the Variable View window.

Epoetin alfa (Epogen) and darbepoetin alfa (Aranesp) are used in anemia caused by chemother- apy or renal failure generic isoniazid 300 mg on line medications a to z. It inhibits xanthine oxidase and is frequently used during chemotherapy to prevent acute tumor cell lysis that results in severe hyperurice- mia and nephrotoxicity cheap 300mg isoniazid otc medicine 7 years nigeria. Oprelvekin (Neumega) is a recombinant interleukin that is indicated for chemotherapy- induced thrombocytopenia as well as for prophylaxis of this potentially dangerous complication purchase 300mg isoniazid with visa schedule 9 medications. Amifostine (Ethyol) is a cytoprotective agent that is dephosphorylated to active free thiol buy 300mg isoniazid free shipping symptoms gallstones, which then acts as a scavenger of free radicals. It is also used to reduce xerostoma in patients undergoing irradiation of head and neck regions. A second-year medical student finds a few occasional bright red blood in the stool. A fur- hours a week to work in a cancer research labo- ther work-up, including computed tomography ratory. She performs which of the following chemotherapeutic Northern blot analysis on multiply resistant cell agents? A 53-year-old woman with breast cancer undergoes a breast-conserving lumpectomy 2. The pathology report bouts of hypoglycemia with mental status returns with mention of cancer cells in two of changes that are rapidly reversed by eating. Following radia- is not diabetic, and his serum levels of insulin tion therapy, chemotherapy is started that are markedly elevated. A 74-year-old man with a 100-pack/year his- tory of smoking is evaluated for hemoptysis. The bi- agent’s activity is related to its ability to do opsy report is small-cell carcinoma of the lung, what? A 53-year-old man presents with changes in fragmentation bowel frequency and pencil-thin stools with 304 Chapter 12 Cancer Chemotherapy 305 7. Her initial diagnosed with early stage breast cancer, which treatment will include both cyclophosphamide is initially managed by partial mastectomy and and doxorubicin. Her tumor was positive for because of doxorubicin’s well-documented tox- expression of estrogen receptors. Which agent icity, which is would you recommend to this patient to pre- (A) Hemorrhagic cystitis vent relapse? A world-class cyclist was diagnosed with metastatic testicular cancer with lesions in both 12. On physical examination he has signifi- treatment for his condition because he learns cant splenomegaly. His white blood cell count is one of the drugs typically used for his condition dramatically elevated, and the physician sus- could ultimately compromise his pulmonary pects leukemia. Which of the following is included in a (9:22) translocation, the Philadelphia chromo- the standard regimen and is associated with his some, confirming the diagnosis of chronic mye- feared complication? A 35-year-old otherwise healthy man presents with fullness in the inguinal region 13. A 54-year-old woman complains of head- swollen lymph nodes in the supraclavicular aches, nausea, and vomiting. A 42-year-old premenopausal woman history of prostate cancer had his prostate recently underwent partial mastectomy and removed 10 years ago. His prostate-specific radiation therapy for a small tumor in her antigen levels have begun to rise again, and he breast. There were no lymph nodes involved, complains of back pain, suggesting metastatic and the tumor was estrogen-receptor positive. Which of (A) Anastrozole the following is a concerning side effect of (B) Leuprolide tamoxifen? A 56-year-old woman with a significant (E) Hypotension smoking history was diagnosed with small-cell lung cancer 2 years ago and was successfully treated. Streptozocin is toxic to b cells of the islets of Langerhans in the pancreas and is therefore used in the treatment of insulinomas. Melphalan is a derivative of nitrogen mustard used to treat multiple myeloma, melanoma, and carcinoma of the ovary. Vinca alkaloids such as vinblastine block chromosomal migration and cellular differentiation. Leuprolide is used to treat hormone-sensitive prostate cancer, and tamoxifen is used to treat breast cancer. Paclitaxel is often used in the treatment of breast as well as ovarian and lung cancer. Its main toxicity is myelosuppression and peripheral neuropathy that usually manifests as numbness and tingling in the distal extremities. Blood in the urine can indicate hemorrhagic cystitis, a complication of cyclophosphamide use. Shortness of breath can result from pulmonary fibrosis secondary to busulfan or bleomycin use. Etoposide is used in the treatment of small-cell lung carcinomas as well as tes- ticular tumors. Before using this agent, a thorough cardiac evaluation is required, including an echocardiogram or nuclear medi- cine scan of the heart. Bleomycin is included in the treatment of metastatic testicular neoplasms and can cause pulmonary fibrosis. Busulfan can also cause pulmonary fibrosis; however, it is not used in the treatment of testicular neoplasms. Cisplatin is highly emetogenic and can cause nephrotoxicity as well as ototoxicity. Aminoglutethimide is an inhibitor of steroid synthesis used in Cushing syndrome as well as some cases of breast cancer. Dactinomycin is a pro- tein synthesis inhibitor used to treat such pediatric tumors as rhabdomyosarcoma and Wilms tu- mor. Anastrozole is an aromatase inhibitor used to inhibit estrogen synthesis in the adrenal gland, a principle source in postmenopausal women. Hydroxyurea is used in the treat- ment of some leukemias as well as myeloproliferative disorders. Many traditional chemotherapy agents inhibit cell cycle progression at vari- ous check points. Temozolomide is an orally active alkylating agent related to dacarbazine used along with radiation for the treatment of glioblastoma multiforme and other high-grade astrocy- tomas. Thioguanine and mercapto- purine are purine analogues that are used primarily in acute lymphoblastic leukemia. Cisplatin is also often used with radiation in tumors of the lung, head, and neck. Anastrozole is used in breast cancer in postmenopausal women to decrease estrogen levels. Tamoxifen is also used in breast cancer to inhibit estrogen-mediated gene transcription. Patients with estrogen receptor-positive tumors benefit from tamoxifen adjunct treatment. It, however, carries a risk of thromboembolism as well as the potential to develop en- dometrial cancer. Many tra- ditional chemotherapeutic agents are associated with myelosuppression, and in fact, that is the mechanism for the effects against leukemias. The antibiotic chloramphenicol has been associ- ated with both myelosuppression and aplastic anemia. Toxicology is concerned with the deleterious effects of physical and chemical agents (includ- ing drugs) in humans (Table 13-1). Toxicity refers to the ability of an agent to cause injury; hazard refers to the likelihood of injury.

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