Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non–Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. @*Materials and Methods@#Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. @*Results@#At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. @*Conclusion@#Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Ultrasonic Activation of a Bioceramic Sealer and Its Dentinal Tubule Penetration: An In Vitro Study

Background: The root canal sealers form an important component of the three dimensional obturation of the root canals. Moreover, the penetration of the sealers into the dentinal tubules is a desirable phenomenon for their adequate sealing and antibacterial action. The aim of this study was to evaluate the effects of ultrasonic activation on the intratubular penetration of bioceramic root canal sealer. Methods: Eighty extracted human mandibular premolars were divided into 2 groups (n =40) according to the sealer activation method used to obturate the root canals instrumented with F3 Pro-Taper instruments .The canals were obturated using Protaper F3 guttapercha cones. Previously, the bio ceramic sealer was labeled with rhodamine B dye to allow analysis under a confocal microscope. The two groups were: UA (ultrasonically activated) and NA (no activation; control). All samples were sectioned at 3 and 8 mm from the apex. The percentages of dentinal sealer penetration segments of canal were analyzed. Results: Students T test was performed for the statistical analysis and we found that there was a significant increase in tubular penetration for the ultrasonic activation group.Conclusion: Use of ultrasonic activation of a bioceramic sealer promoted greater dentinal sealer penetration.

Determine the diagnostic accuracy of HbA1C for detection of diabetes mellitus by taking fasting blood sugar as gold standard

Background: HbA1c is now formally endorsed in many countries as a diagnostic test for [type 2] diabetes as well as for monitoring, although some debate still continues regarding its applicability for diagnosis

Objective: The objective of the study was to: Determine the diagnostic accuracy of HbA1C for detection of diabetes mellitus by taking fasting blood sugar as gold standard. Study Design: Cross Sectional Study [Validation]. Setting: Medical department, Allied Hospital, Faisalabad. Duration of Study: 6 Months Duration from 25-02-2015 to 25-08-2015

Methodology: A total of 145 cases with more than 40 years of age of either gender were enrolled in the study. Informed consent was taken from each participant of the study from medical department, Allied Hospital, Faisalabad. Information was collected by trainee researcher and comprised age, Gender, address and contact number, HbA1C and Fasting Blood Sugar. HbA1C and Fasting blood sugar was measured by drawing 3cc blood from a peripheral vein after antiseptic measures and sent to pathology laboratory, Allied Hospital, Faisalabad where it was reported by Pathologist. All the information was collected on Performa by Principal Investigator

Results: In our study, 71.72% [n=104] were between 40-60 years while 28.28% [n=41] had >60 years of age, mean +/- sd was calculated as 56.75 +/- 6.45 years, 52.41% [n=76] were male and 47.59% [n=69] were females, frequency of diabetes mellitus on gold standard was recorded as 26.21% [n=38] while 73.79% [n=107] had no findings of the morbidity. Diagnostic accuracy of HbA1C for detection of diabetes mellitus by taking fasting blood sugar as gold standard was calculated for sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate as 78.95%, 83.17%, 62.15%, 91.75% and 82.07% respectively

Conclusion: We concluded that the diagnostic accuracy of HbA1C at cutoff point more than 6.15% for detection of diabetes mellitus by taking fasting blood sugar as gold standard is high and this modality can be used in our population

Comparison of fenofibrate versus gemfibrozil in the management of hypertriglyceridemia in patients with coronary heart disease

Objectives: To compare the mean triglyceride [TG] level with fenofibrate versus gemfibrozil in patients presenting with acute coronary syndrome. Design: Randomized controlled trial [RCT] Setting: Department of Medicine Allied Hospital, Faisalabad. Period: From August 2014 to June 2015

Methodology: A total of 100 cases [50 in each group] were included in the study. Patients were randomly divided in tow groups by using lottery method. In group-F, patients were prescribed fenofibrate capsule of 201mg/day and in group-G, patients prescribed gemfibrozil 600mg twice/day. Patients were followed for 12 weeks

Results: Mean age of the patients was 59.40 +/- 10.93 and 59.04 +/- 10.77 years in group-A and B, respectively. In group-F, 30 patients [60.0%] were male and 20 patients [40.0%] were female while in group-G, 27 patients [54.0%] were male and 23 patients [46.0%] were female. In group-F, 25 patients [50.0%] were obese and in group-G, 27 patients [54.0%] were obese. Unstable angina was observed in 27 patients [54.0%] of group-F and in 17 patients [34.0%] of group-G. NSTEMI [non ST segment elevated MI] noted in 10 patients [20.0%] of group-F and 20 patients [40.0%] of group-G while STEMI [ST segment elevated MI] was present in 13 patients [26.0%] in both groups. When comparison of triglyceride level was made, mean triglyceride level in group-F was 172.76 +/- 21.52 mg/dl and in group-G 214.12 +/- 44.09 mg/dl. Statistically significant difference was observed between two groups [p<0.001]

Conclusion: Mean triglyceride level at 12 weeks was lower in fenofibrate group as compared to gemfibrozil group. This study favorably supports the use of fenofibrate in the treatment of hypertriglyceridemia in patients presenting with acute coronary syndrome

Management of a maxillary second premolar with an S-shaped root canal – An endodontic challenge.

Knowledge of dental anatomy and its variations is essential for the success of endodontic treatment Complex and unusual root canal morphology is an often occurring phenomenon. One such variant root canal morphology is the ‘S’ shaped or bayonet shaped root canal. The unique morphology of S-shaped root canals often pose utmost challenges in their endodontic management routine periapical radiographs aids in assessing these morphological variations in the root canal system This case report discusses endodontic treatment of a maxillary second premolar with an ‘S’ shaped root canal.

Female space between social reality and subtraction dramatic

Background: This study aims at knowing the Female Space between social reality and subtraction dramaticit also aims to identify the relationship between social reality and subtraction dramatic quality of the spaces in the plays of the Egyptian writer Jacob Sharon and British writer Ted Hughes, The study used content analysis form, and compare the results statistically and then test the validity of the assumptions and the interpretation of results and the study found a set of results that the most important

Statistical Analysis Methods: z-test 2-chi-square

Results: The study validated the first and main hypothesis of the study, which states that: "There is a statistically significant relationship between the picture presented for the child in the plays and the image formed by the cultural heritage in a patriarchal society", study proved the health of the second hypothesis of the study,, which states that: "There is a statistically significant relationship between the marginalization of female roles within a patriarchal society and the marginalization of female roles in the play texts where the male child assume leadership roles in accordance with the provisions of the play of the study sample", proved to study the health of third hypothesis of the study, which states that: "There are significant differences between the social roles of child male differences female mother was in the play texts between the study sample and social roles in a patriarchal society in accordance with the provisions of the play of the study sample", and proved to study the health of fourth hypothesis of the study, which states that: "There are significant differences between the functional roles of the child zkra or female fa theatrical texts of the study sample and the functional roles of the child [male and female] in a patriarchal society in accordance with the provisions of the play of the study sample

Comparison of electrocardiography with echocardiography in terms of concurrence of results in the diagnosis of left ventricular hypertrophy

Introduction: Left ventricular hypertrophy, common in hypertension, is an adaptive state of the heart to increase in wall stress. LVH has important prognostic implications for patients with hypertension. In detection of LVH, Echocardiography is considered to be superior to electrocardiography in patients with hypertension

Objectives: To compare the findings of electrocardiography with echocardiography in terms of concurrence of results in the diagnosis of left ventricular hypertrophy

Study Design: Cross - sectional study

Place and Duration of Study: Medical Department of Allied Hospital and PINUM Faisalabad from 14-02-2014 to 13-08-2014

Material and Methods: A total of 88 patients were included in this study. After detailed history and examination, all patients had first ECG and then echocardiography

Results: Mean age of the patients was 50.85+6.3 year. Out of 88 cases, 55 patients [62.5%] were male while remaining 33 patients [37.5%] were female. Mean height of the patients was 1.69+0.10 meter, mean weight was 66.1+9.86 kg and mean BMI was 23.38+1.20. Out of 88 cases, 67 cases were positive on echocardiography and 39 cases were positive on electrocardiography [ECG]. Out of these 39 cases 37 cases were true positive, 2 cases were false positive

Conclusion: The results show that electrocardiogram has low sensitivity and low NPV for detecting LVH as compare to echocardiography. These findings are relevant for physiological LVH and should not be extrapolated to detection of hypertrophic cardiomyopathy. In clinical practice, echocardiography alone should be used to exclude LVH

Prevalence of H. pylori

Acid peptic disease is a world wide problem among all the age groups and both sexes. Duodenal ulcer is common as compared to gastric ulcer. Its prevalence being 4:1 in USA and UK and 5:1 in Pakistan. Etiology of peptic ulcer is almost certainly multi-factorial. Basic paradigm for ulcer disease is the imbalance between the digestive activity of acid and pepsin and the protective mechanism in place to resist mucosal digestion. Over the past few years a new line of thought has been evolved after isolating spiral campylobacter like organism from antral biopsy specimens. H pylori is now considered to be an important if not the only causative agent of gastritis and peptic ulcer disease. The dictum; No acid - No ulcer summarized the pathogenesis of peptic ulcer disease but new dictum seems to be; No H. pylori -No ulcer, as over 90% of Duodenal ulcer and 70% of Gastric ulcer patients are infected by H. Pylori. Aim of the study was to evaluate the prevalence of H. pylori among duodenal ulcer patients at Faisalabad District and its suburbs. Descriptive Study. From Mar 2008 to Oct 2008. 50 patients [40 males, 10 females] belonging to Faisalabad District and surrounding areas with upper gastrointestinal symptoms of acid peptic disease and endoscopy proved duodenal ulcer were subjected to gastric antral mucosal biopsies for evaluation of the H. Pylori status with the help of unease test and histological examination of biopsy specimen. Epigastric pain was the most frequent symptom 90%. [46 out of 50 patients]. 92% showed evidence of H. pylori infection. Maximum incidence of H. pylori was recorded in age group IV [46-55 years]. Maximum number of patients was skilled workers [35 out of 50] 70%. 80% of the patients belonged to lower and middle class. Percentage of H. pylori positivity was 89.1% and 84.34%. Acceptance of contributory role and high prevalence rate of H. pylori instigates us for addition of antimicrobial treatment to the conventional treatment with H2 Blockers and PPls which is cost effective and alter the course of the disease

Chronic hepatitis C virus infection; association with type 2 diabetes mellitus

[1] To seek the association between chronic HCV infection and type 2 diabetes, mellitus. [2] To verify the effect of age, sex, socioeconomic status, obesity and presence of cirrhosis on the association of chronic HCV infection. Case control study. DHQ Hospital, Faisalabad. The subjects were divided into two groups. One was with positive anti-HCV antibody on ELISA method and other was without liver disease and negative for anti-HCV. Both the groups contained 500 subjects each and were selected according to the inclusion and exclusion criteria. After a brief interview regarding age, residence, family history of diabetes, socioeconomic status, both the groups underwent weight and height measurements. The body mass was calculated according to the formulae. Ultrasonography of abdomen was done of all the patients of study groups to assess the liver status. Chi - square test was applied to see the association and then odds ratio was calculated to check the strength of association. Diabetes mellitus was detected in 174 patients [34.8%] out of 500 patients in the group Aas compared to 30 patients [6%] out of 500 patients in the group B. having chi-square value of 127.69 and significance of 0.000 with HCV +/ HCV- Odds ratio 0.120 and 95% C 10.079-0.181. There is strong association between HCV infection and type 2 diabetes mellitus. Severity of Liver Disease was strong associated factor

Fiberoptic bronchoscopy; diagnostic role, a local experience

To demonstrate the usefulness of Bronchoscopy as a diagnostic tool in various pulmonary disorders. Prospective study. Nawaz Medicare Hospital Faisalabad. June 2004 to December 2007. This study was conducted on 52 patients, 37 were male and 15 were female. Their ages ranged from 26 to 85 years. These patients who under went Bronchoscopy were either suspected cases of bronchogenic carcinoma or had difficult to treat un-resolving pneumonias. Endobronchial biopsies and bronchial aspirates were obtained. In the patients suspected of bronchogenic tumor 66.67% patients turned out to be positive on endobronchial biopsies. Bronchial aspirates were diagnostic in 73.32% cases of un-resolving pneumonias. The commonest symptoms in patients under going Bronchoscopy were haemoptysis and cough. Bronchoscopy is very useful in the diagnosis of suspected cases of bronchogenic carcinoma. Bronchial aspirates are helpful in the diagnosis of un-resolving pneumonias

Pattern of dyslipidemia CRF in patients with CRF

[1]To find the pattern of dyslipidemias in patients with CRF. [2.]To compare the results with international studies. Prospective observational study. In Medical Unit I, II, III and Nephrology ward of Allied Hospital Faisalabad. [06 Months] From: Nov 2004 to April 2005. Allied Hospital is a teaching hospital attached with Punjab Medical College Faisalabad having 1100 beds. Chronic renal failure, a very common disease, is accompanied by many complications. One of such complications is abnormality of lipids. The lipids are disturbed in a characteristic manner. This disturbed lipid pattern predisposes the patients to atherosclerotic complications and increased mortality due to cardiovascular and cerebrovascular accidents. Present study was conducted to determine the pattern of dyslipidemias in patients of CRF.50 patients diagnosed to have CRF were subjected to fasting lipid profile, irrespective of cause and sex. Maximum patients had elevated triglyceride levels [46%]. A considerable percentage [16%] had decreased HDL levels and a small percentage had elevated LDL [4%]. Total lipids were found to be elevated in 04 patients [8%]. All the patients with elevated total lipid were suffering from diabetes mellitus. Total cholesterol was elevated in 08 patients [16%]. This disturbed lipid pattern has role in atherosclerosis. The patients of CRF who are already having disturbed endothelial function are more prone to it

Diagnostic role of endoscopy; an experience at Faisalabad

To see the usefulness of Endoscopy in patients with various gastrointestinal manifestations. Prospective study. Department of medicine and gastroenterology Allied Hospital Faisalabad January 2005 to July 2005, This study was conducted on 500 patients presented to us with various gastrointestinal manifestations of either sex and between 13-70 years. 260 patients were Males and 237 were Females. Most common indication was epigastric pain. 60.4% of the patients had organic lesion. Endoscopy was maximally positive in inpatients [91.86%]. Most common lesion was in stomach i.e. gastritis. Collectively ulcerative lesions came out to be 27.30%. Diagnostic yield of Endoscopy is undoubtedly very high if the patient selection is done in a meticulous way

Role of amantadine in treatment of chronic hepatitis C

Background: Interferon afla [IFN-alfa] is the only effective treatment for patients with Chronic hepatitis C. Forty percent of patients have an initial response to therapy. But most subsequently relapse. Amantadine, an antiviral agent, in addition ability, of preferably concentrating in liver, has shown a role in reducing hepatic inflammation and suppressing viral replication. The aim of this study was to assess the efficacy and safety Of amantadine for treatment of chronic infection with hepatitis C virus [HCV]. Design: Prospective study. Period: From January 2002 to Dec 2003, Setting: Allied Hospital, Faisalabad

Methods: Fifty patients either naive or interferon resistant, with age range of 18-65 years, were enrolled and treated with amantadine 100 mg orally twice daily for six month. Control groups included the same cohort followed of therapy for 12-18 month or during therapy with interferon. All patients were assessed for safety. Tolerance and efficacy at the end of every month during treatment was completed. Patients were followed up for an additional six month to assess durability of response. The primary end - point were loss of detectable HCV-RNA six month after cessation of therapy

Findings: Out of 50 patients treated for six months with amantadine compared to intervals without therapy or to interferon therapy, 17 [34%] had normal serum alanive aminotransferase [ALT] values and had cleared HCV RNA in serum by the end of treatment. The sustained virological response was found in 11 patients with an undetectable serum HCV RNA level six month after therapy Baseline low serum HCV RNA levels were associated with higher rates of Response. During the therapeutic trial, amantadine caused no potential treatment limiting side effects but had a good safety profile

Interpretation: Therapy with amantadine results in biochemical as well as virological response both in the naive and interferon resistant cases of chronic hepatitis C

Prevalence of retinopathy in hypertensive patients

Objective: The objectives of this study were to find out the prevalence of hypertensive retinopathy among hypertensive patients in this area of Pakistan and grading of hypertensive retinopathy at the time of examination according to the Keith-Wagener retinal changes classification for hypertension. Study Design: An observational study. Period: 5½ months Setting: Outdoor/emergency department as well as in medical unit - II of Allied Hospital, Faisalabad

Material and Methods: Three hundred consecutive patients with hypertension of either sex and between 20-85 years of age were examined. Opthalmoscopy was done after dilating the pupil with 1% Mydriacyl and retinopathy graded according to Keith-Wagener Classification

Results: Among these patients, 168 had the finding of hypertensive retinopathy, with overall prevalence of 56%. Out of these 168 patients, 70 had grade I, 75 had grade II, 18 had grade III and 05 had grade IV changes according to the Keith-Wagener Classification of hypertensive retinopathy. Among these 168 patients with hypertensive retinopathy, 64 were males and 104 were females, with overall prevalence in males 58.18% and in females 54.73%. It is found that prevalence of hypertensive retinopathy is maximum in patients with 50 years of age or above. The prevalence of hypertensive retinopathy increases with the duration of hypertension and is maximum in patients with duration of 10 years or more. Two hundred twenty five [225] patients were taking single drug and out of these 110 patients were found to have retinopathy with prevalence of 48.8%, 40 patients were taking combination therapy and out of these 34 patients were found to have retinopathy with prevalence of 86%. The remaining 35 hypertensive patients who had never taken medicine for their B.P control, out of these 35, 22 patients were found to have hypertensive retinopathy with prevalence of 62.8%

Conclusion: Prevalence of hypertensive retinopathy in our population is quite high, seen in both sexes and almost in all age groups. It increases with duration of the disease, higher in patient who are taking combination of drug as compared to those who were on single drug

Incidence of ischemic heart disease in patients with non insulin dependent diabetes mellitus

Objective: To find out the incidence of IHD in patient with NIDDM. To study the pattern of clinical presentation of IHD in diabetic patient. To create awareness in the population that IHD is more prevalent in diabetic patient. Design

Prospectus Study Setting: Allied Hospital Faisalabad: Period: Apr 2003 to Sep 2003

Material and Methods: One hundred with previously diagnosed none insulin dependent diabetes mellitus [NIDDM] investigations of duration of their illness were studies. Among 100 patients, 78 were male and 22 were female

Results: Among the 100 patients studied, 17 had evidence of IHD and out these 5 [29.5%] were male and 12 [70.5%] were female. Amongst the patient having IHD, 5 [29.5%] had typical symptoms of angina with or with out ECG change consistent with IHD. Another 6 [35%] had atypical symptoms of IHD with ECG changes. Typical changes of IHD was found in 6 patients

Conclusion: The incidence of IHD is higher in diabetic patient as compare to general population. The presentation of IHD is often atypical in diabetic patients

Stroke in hypertensive patients; a scan based 100 case study

Objective: To compare the incidence of intracerebral haemorrhage and cerebral infarction in hypertensive patients in stroke. Design: Prospective study: Setting: Medical Unit II Allied Hospital Faisalabad. Period: From 1[st] Aug 2000 to 15[th] April 2001

Material and Method: 100 patients admitted to medical unit II, with a completed stroke along with hypertension. Stroke was suspected on clinical examination and for confirming the diagnosis, CT scan facilities were made available. Out of 100, 65 were males and 35 were females. 73 patients had infarctive stroke, 22 had a haemorrhagic stroke and 5 patients had subarachnoid hemorrhage

Results: Patients were divided into various sub groups according to age, sex, type of stroke and risk factors. The results were tabulated as per outcome on CT brain. 73 patients had infarctive stroke, 22 had a hemorrhagic stroke and 5 patients had SA hemorrhage

Conclusion: Hypertension is risk factor in stroke and should be properly controlled

Hepatitis B and C virus and nephrotic syndrome

Nephrotic syndrome is a common disorder that affects all age groups. Etiology is variable ranging from infection to malignancy. Lately Hepatitis B and C viruses have been found to have high correlation with Nephrotic syndrome. The microscopic renal picture is different depending upon age groups

Objectives: objective of this study was to determine how prevalent is HBV and HCV in adults with Nephrotic syndrome in this region of Pakistan

Period: jan 1997 to Oct 1998

Setting: allied Hospital PMC, Faisalabad

Material and methods: all patients between age 14 and 60 years who were having Nephrotic syndrome with all known secondary causes having been ruled out, underwent Percutaneous Renal Biopsy

Results: among 50 patients 34 were positive for HCV and 3 were positive for HBV. Commonest microscopic lesion was Membrano-Proliferative Glomerulonephritis

Conclusions: there is high prevalence of HCV in adult Nephrotic syndrome like some other countries

Acute myocardial infarction; study of in-hospital complications in patients treated with streptokinase versus control

Objectives: to evaluate the benefits of early streptokinase therapy in patients with acute myocardial infarction

Settings: district Headquarters and Allied Hospital, Faisalabad

Period: 1st January, 1997 to 30th May, 1997. Results: Out of 102 patients included in this study male to female ratio was 1.6 to 1.Forty seven percent received streptokinase therapy and 53% were denied due to any contraindication. The mean age was 52 years with 82.5% above the age of 40 years. 66.7% in both groups were in Killip Class-I, while 8.3% in streptokinase group and 3.7% in control group were in Killip Class-IV. The overall mortality was 17.6% but 29.8% in control group and only 4.2% in streptokinase group expired. The rhythm disturbances were more in streptokinase group. 66.7% presented late, and mechanical complications were more in the control group

Conclusion: the early streptokinase therapy lowers the in-hospital mortality but more public awareness is required for early reporting and efforts should be made for the availability of streptokinase for the poor community