BACKGROUND – THE STUDY QUESTION
Background • In type 2 diabetes, the body’s cells is resistance to insulin which results in excess blood sugar.
• Canagliflozin inhibits sodium-glucose cotransporter-2.
• the kidney-based inhibition reduces the rate at which glucose is reabsorbed. The latter results in increased glucose excretion via urine and reduced plasma glucose.
• The drug is indicated for diabetes and can be administered for hypertension, obesity and albuminuria.•
Previous trials • CANVAS- Began in November 2009 and ended March 2014. This trial occurred before the approval of canagliflozin by the FDA. The initial purpose was to determine cardiovascular safety, and assess adverse effects associated with the Canagliflozin
• CANVAS-R- Began in January 2014 and ended May 2015. This trial is post market research to measure cardiovascular safety and measure effects on albuminuria
Why this study? • Establishing canagliflozin’s effects on the cardiovascular and renal systems, alongside general safety concerns when patients are put von the drug.
GENERAL STUDY OVERVIEW
Funding • Janssen Research and Development: CANVAS
• CANVAS-R Clinical Trials.gov • Two interested bodies funding the research to inform their practice
Trial design • Double-blind, placebo-controlled
• Trial and randomized trial designs • Randomized trials enabled accuracy and bias during the study
Null Hypothesis • Death resulted from any causes like progression of albuminuria, cardiovascular complications and/or heart failure.
• Death could not be directly caused and/or influenced by the factors mentioned. The latter were not the basis of the research.
Objectives • Establishing the outcomes of canagliflozin on cardiovascular complications among type 2 diabetes patients. • The outcomes of the drug inform its indications and contraindications for diabetic patients.
Enrollment • Patients aged averagely 63.3 years. 64.2% males and 35.8% females.
• 65.6% of the specimen suffered from the disease and the mean duration for diabetes was 13.5 years.
• The nature of the enrollment enables collection of the most actionable and relevant data on the drug and its implications on patients.
Inclusion criteria • Raw data to illustrate and test the theme – males and females suffering from the disorder were randomly selected and subjected to the study
• Patients with a history of cardiovascular illnesses are primary targets
• Childbearing women, or simply fertile women, must test negative for the hormone, beta-HCG, during screening. • The participants provided raw data following administration of the drug
Exclusion criteria • Qualitative methodology: hazard ratio of 1:3 • The hazard ratio was integral to the registration of the adverse effects of the drug among the participants.
Randomization • Centrally-executed randomization via a Web-based response system.
• They are also accompanied by permuted blocks.
• Computer-generated schedules were used. • Computer-generated randomization enhances accuracy and potentiate the validity of the outcomes
Interventions • Monitoring patients
• Follow-up programs on patients to which the drug is administered.
• CANVAS participants were assigned in the ration of 1:1:1.
• They received a placebo, 100 mg and 300 mg canagliflozin
• CANVAS-R were assigned the ration 1:1
• They received a placebo and a canagliflozin.
• Canagliflozin was initially administered daily, 100 mg and after the 13th week, 300 mg.
• Dose consumption: daily dose intake following a 2-weeksingle-blind run-in period where placebo was consumed,
• • Follow-ups enhanced the accuracy and validity of the study
• Controlling and monitoring the progress of the groups is key to the development of the concept.
Primary Endpoints • Non-fatal, MI or stroke and CV mortality • • • Patients are likely to die of cardiovascular complications mentioned earlier
Secondary Endpoints • All causes of mortality • Some cardiovascular and systemic complications may not result in patient death even though they are related to the condition
Statistical analyses • Statistics indicate the effectiveness of the drug on diabetic patients. The landscape of the statistical revelation is quite dynamic and extensive, as displayed in the article • the implications of the drug is displayed in the article. They display a multidimensional effects and implications of the drug and its effectiveness among the target group
Enrollment • Patients with extensive periods of the disease potentially provide the most relevant results on the same. • Participants must be carefully enrolled and recruited in the study process to obtain best results.
Monitoring • Frequent participant follow-up and evaluation • Participant evaluation and follow-up is necessary for analyzing the progress of their conditions.
Baseline characteristics • Type 2 diabetes patients likely to face cardiovascular complications, amputation and possibly death.
• Amputation and cardiovascular complications are probable among type 2 diabetes patients. The cardiovascular complications can result in death.
Primary Outcome Composite death resulting from cardiovascular complications, nonfatal stroke and/or nonfatal myocardial infarction.
• Nonfatal stroke and myocardial infarction are possible triggers of death among type 2 diabetes patients
Secondary Outcomes • Death resulted from cardiovascular causes, hospitalization courtesy of heart failure and/or progression of albuminuria. • Cardiovascular complications like heart failures and/or albuminuria’s progression do not independently trigger death
Adverse Events • Pharmacological adverse reactions
• Nonresponsive participants during follow-up • The drug increased chances of amputation
Type 2 diabetes patients treated with canagliflozin displayed lower cardiovascular stress and complications than those who did not, and the converse is true
• The article/study benefited from a large sample size, combined trials, length trial durations, high standards of trials and a wide breadth of participants.
• Possible renal protection
• Patients who received canagliflozin displayed low hospitalization rates than those who received a placebo
• Moderate events around essential outcomes, especially paucity of events concerning end-stage kidney disease.
• Large number of studies and analysis that increase the probability of false results.
• Advantageous to weight and hypertension
• Decreased cardiovascular hospitalization
• Canagliflozin is an effective drug for reducing cardiovascular-related mortality among type 2 diabetes
• Increasing amputation cases among type 2 diabetes patients
• Terminating randomized therapy, alongside administration glucose-reducing medications, among members of the placebo group, during the trial, is a potential account for the convergence and increase in hemoglobin levels.
• The latter may have resulted underestimation of other advantages and disadvantages of canagliflozin.
Canagliflozin is a remarkable drug for diabetes-related cardiovascular complications. It prevents amputation and reduces mortality rates.
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12. PMID: 28605608
Text review of this exposition: This page of the exposition has 2111 words. Download the full form above. The United States is home to probably the most infamous and productive chronic executioners ever. Names, for example, Ted Bundy, Gary Ridgeway, and the Zodiac Killer have become easily recognized names because of the terrible idea of their wrongdoings. One of the most productive chronic executioners in American history is John Wayne Gacy. Nicknamed the Killer Clown due to his calling, Gacy assaulted and killed at any rate 33 adolescent young men and youngsters somewhere in the range of 1972 and 1978, which is one of the most elevated realized casualty checks. Gacy's story has become so notable that his wrongdoings have been included in mainstream society and TV shows, for example, American Horror Story: Hotel and Criminal Minds. Scientific science has, and keeps on playing, a significant function in the understanding of the case and recognizable proof of the people in question. John Wayne Gacy's set of experiences of sexual and psychological mistreatment was instrumental in arousing specialist's curiosity of him as a suspect. John Wayne Gacy was conceived on March 17, 1942, in Chicago, Illinois. Being the main child out of three youngsters, Gacy had a stressed relationship with his dad, who drank vigorously and was regularly oppressive towards the whole family (Sullivan and Maiken 48). In 1949, a contractual worker, who was a family companion, would pet Gacy during rides in his truck; in any case, Gacy never uncovered these experiences to his folks because of a paranoid fear of requital from his dad (Foreman 54). His dad's mental maltreatment proceeded into his young grown-up years, and Gacy moved to Las Vegas where he worked quickly in the rescue vehicle administration prior to turning into a funeral home specialist (Sullivan and Maiken 50). As a morgue chaperon, Gacy was intensely engaged with the preserving cycle and conceded that one night, he moved into the final resting place of a perished adolescent kid and stroked the body (Cahill and Ewing 46). Stunned at himself, Gacy re-visitations of Chicago to live with his family and graduates from Northwestern Business College in 1963, and acknowledges an administration student position with Nunn-Bush Shoe Company. In 1964, Gacy is moved to Springfield and meets his future spouse, Marlynn Myers. In Springfield, Gacy has his subsequent gay experience when a colleague unsteadily performed oral sex on him (London 11:7). Gacy moves to Waterloo, Iowa, and starts a family with Myers. In any case, after routinely undermining his significant other with whores, Gacy submits his originally known rape in 1967 upon Donald Vorhees. In the coming months, Gacy explicitly mishandles a few different young people and is captured and accused of oral homosexuality (Sullivan and Maiken 60). On December 3, 1968, Gacy is indicted and condemned to ten years at the Anamosa State Penitentiary. Gacy turns into a model detainee at Anamosa and is conceded parole in June of 1970, an only a short time after his condemning. He had to migrate to Chicago and live with his mom and notice a 10:00PM check in time. Not exactly a year later, Gacy is accused again of explicitly attacking a high school kid however the young didn't show up in court, so the charges were dropped. Gacy was known by numerous individuals in his locale to be a devoted volunteer and being dynamic in network governmental issues. His part as "Pogo the Clown" the comedian started in 1975 when Gacy joined a neighborhood "Happy Joker" jokester club that routinely performed at raising support occasions. On January 3, 1972, Gacy submits his first homicide of Timothy McCoy, a 16-year old kid going from Michigan to Omaha. Asserting that McCoy went into his room employing a kitchen blade, Gacy gets into an actual squabble with McCoy prior to cutting him over and over in the chest. In the wake of understanding that McCoy had absentmindedly strolled into the stay with the blade while attempting to get ready breakfast, Gacy covers the body in his creep space. Gacy conceded in the meetings following his capture that slaughtering McCoy gave him a "mind-desensitizing climax", expressing that this homicide was the point at which he "understood passing was a definitive rush" (Cahill and Ewing 349). Right around 2 years after the fact, Gacy submits his second homicide of a unidentified young person. Gacy choked the kid prior to stuffing the body in his storeroom prior to covering him (Cahill 349). In 1975, Gacy's business was developing rapidly and his hunger for youngsters developed with it. Gacy regularly baited youngsters under his work to his home, persuading them to place themselves in cuffs, and assaulting and tormenting them prior to choking them (Cahill 169-170). The vast majority of Gacy's homicides occurred somewhere in the range of 1976 and 1978, the first of this time occurring in April 1976. Huge numbers of the adolescents that were killed during this time were covered in a creep space under Gacy's home. For the rest of the killings, Gacy confessed to losing five bodies the I-55 scaffold into the Des Plaines River; notwithstanding, just four of the bodies were ever recuperated (Linedecker 152). In December 1978, Gacy meets Robert Jerome Piest, a 15-year old kid working at a drug store and extends to him an employment opportunity at Gacy's firm. Piest advises his mom regarding this and neglects to restore that night. The Piest family documents a missing individual's report and the drug specialist illuminates police that Gacy would doubtlessly be the man that Jerome addressed about a work. When addressed by the police, Gacy denied any association in Piest's vanishing. Nonetheless, the police were not persuaded, and Gacy's set of experiences of sexual maltreatment and battery incited the police to look through his home. Among the things found at Gacy's home were a 1975 secondary school class ring with the initials J.A.S., different driver's licenses, cuffs, garments that was excessively little for Gacy, and a receipt for the drug store that Piest had worked at. Throughout the span of the following not many days, examiners got numerous calls and tips about Gacy's rapes and the baffling vanishings of Gacy's representatives. The class ring was at last followed back to John A. Szyc, one of Gacy's casualties in 1977. Futhermore, after inspecting Gacy's vehicle, specialists found a little group of filaments looking like human hair, which were shipped off the labs for additional examination. That very night, search canines were utilized to recognize any hint of Piest in Gacy's vehicle, and one of the canines demonstrated that Piest had, indeed, been available in the vehicle. On December 20, 1977, under the pressure of steady police observation and examination, Gacy admits to more than 30 homicides and advises his legal counselor and companion where the bodies were covered, both in the creep space and the waterway. 26 casualties were found in the slither space and 4 in the waterway. Gacy is captured, indicted for 33 killings, and condemned to death by deadly infusion. He endeavored a craziness supplication however was denied, and was executed on May 10, 1994. There were a few scientific markers that examiners used to attach Gacy to the homicides. A portion of these include fiber examination, dental and radiology records, utilizing the disintegration cycle of the human body, and facial recreation in recognizing the people in question. Agents discovered strands that looked like human hair in both Gacy's vehicle and close to the slither space where the bodies were covered. Notwithstanding these hair tests, agents likewise discovered filaments that contained hints of Gacy's blood and semen in a similar region. Blood having a place with the casualties was found on a portion of the strands, which would later legitimately attach Gacy to the violations. The filaments in Gacy's vehicle were investigated by measurable researchers and coordinated Piest's hair tests. Moreover, the pursuit canines that discovered that Piest had been in Gacy's vehicle demonstrated this by a "demise response", which told agents that Piest's dead body had been within Gacy's vehicle. Out of Gacy's 33 known casualties, just 25 were ever convincingly distinguished. A large number of Gacy's casualties had comparative actual depictions and were along these lines hard to recognize by absolutely asking people in general. To recognize the people in question, specialists went to Betty Pat Gatliff, a pioneer in scientific science and facial remaking. Facial remaking is the way toward reproducing the facial highlights of a person by utilizing their remaining parts. Certain facial highlights, for example, facial structures, nasal structure, and by and large face shape can be valuable in distinguishing a casualty even long in the afterlife. By utilizing these highlights, and with the assistance of program, scientific examiners can make a picture of an individual's face, which is instrumental in distinguishing casualties after their bodies have rotted. Facial reproduction should be possible in a few measurements. Two-dimensional facial reproductions is utilized with skull radiographs and depend on pre-passing photos and data. Nonetheless, this isn't really ideal in light of the fact that cranial highlights are not generally noticeable or at the correct scale (Downing). To get a reasonable and more precise portrayal of the casualty's face, a craftsman and a measurable anthropologist are generally important (Downing). Three-dimensional facial remaking is finished by models or high goal, three-dimensional pictures. PC programs can make facial reproductions by controlling filtered photos of the remaining parts and use approximations to reproduce facial highlights. These will in general create results that don't look fake (Reichs and Craig 491). Once in a while, examiners will utilize a strategy called superimposition as a method for facial remaking. Shockingly, it's anything but an ordinarily utilized strategy, as it expects examiners to have some information about the personality of the remaining parts they are managing. By superimposing a photo of a person over the skeletal remaining parts, agents can check whether the facial highlights line up with the anatomical highlights, permitting them to recognize a casualty. On account of John Wayne Gacy's casualties, specialists had the option to utilize facial reproduction to recognize nine of the bodies found in the slither space. The accompanying realistic shows the facial recon>GET ANSWER