ABSTRACT
BACKGROUND@#Fourier transform infrared (FTIR) spectroscopy technique has not been used as a diagnostic tool for diabetes in clinical practice. This study was linked to structural changes in hemoglobin (Hb) in type 2 diabetes patients at higher levels of HbA1C using FTIR spectroscopy.@*METHODS@#Fifty-three diabetic patients from the Bahawal Victoria Hospital, Bahawalpur, Pakistan were categorized as group A (6% < HbA1C < 7%; n = 25) and group B (HbA1C ≥9%; n = 28). Another group (group N) of twenty blood samples was taken from healthy people from the Islamia University Bahawalpur, Pakistan. Data from all groups were collected from January 1, 2018 to March 31, 2019. The structure of Hb was studied by FTIR spectroscopy and impact of glucose on the fine structure of HbA1C was estimated.@*RESULTS@#Hb secondary structure erythrocyte parameters were altered by changing glucose concentrations. From FTIR spectra of all three groups it was found that Hb structure was slightly altered in group A, but significantly changed in group B (P < 0.05). There was an increase in β-sheet structure and a reduction in α-helix structure at elevated levels of HbA1C (group B) in type 2 diabetes.@*CONCLUSION@#We suggest that higher level of glycation reflected by increased HbA1C might be a contributing factor to structural changes in Hb in type 2 diabetic patients. FTIR spectroscopy can be a novel technique to find pathogenesis in type 2 diabetes.
ABSTRACT
Objective: Zinc is a vital trace element and its deficiency in cirrhosis might potentiate the development of hepatic encephalopathy. The objective of this study was to assess the zinc levels in serum of patients having viral cirrhosis and compare it with normal healthy controls
Methods: This study was conducted in Department of Gastroenterology, Liaquat National hospital and medical college, Karachi, Pakistan; from January 2014 to December 2014. Total of 45 patients with the mean age of 52.44+/-8.7 years were included. The three groups of patients were made including Child Pugh Class Score B [Group-1], Child Pugh Class C [Group-2] and healthy controls [Group-3] having 15 patients in each group. Zinc levels in serum were evaluated by the help of atomic absorption spectrometry [Normal range50-150 micro g/dl]
Results: Total of 45 subjects was enrolled in this study. Overall prevalence of zinc deficiency was noted in 13[28.9%] patients. Mean value of zinc levels in group 1, 2 and 3 were 68.09+/-20.85, 50.69+/-15.86 and 92.91+/-17.18 micro g/dL respectively. Highly statistical difference was observed in the mean zinc level between three groups p=0.0001. An inverse correlation was observed between Child Pugh Score and the zinc level in serum r=-0.498
Conclusion: Patients suffering from advanced cirrhosis appeared to have lower serum zinc levels.In patients suffering from viral cirrhosis having hepatic encephalopathy, zinc supplementation might improve clinical outcome
ABSTRACT
Objective: The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus [HCV] NS5B polymerase approved for the treatment of chronic HCV infection with genotypes 1 - 4. The objective of the study was to evaluate the interim results of efficacy and safety of regimens containing Sofosbuvir [Zoval] among Pakistani population with the rapid virologic response [RVR2/4 weeks] with HCV infections
Methods: This is a multicenter open label prospective observational study. Patients suffering from chronic Hepatitis C infection received Sofosbuvir [Zoval] 400 mg plus ribavirin [with or without peg interferon] for 12/24 weeks. The interim results of this study were rapid virological response on week 4. Data was analyzed using SPSS version 21 for descriptive statistics
Results: A total of 573 patients with HCV infection were included in the study. The mean age of patients was 46.07 +/- 11.41 years. Out of 573 patients 535 [93.3%] were treatment naive, 26 [4.5%] were relapser, 7 [1.2%] were non-responders and 5 [1.0%] were partial responders. A rapid virologic response was reported in 563[98.2%] of patients with HCV infection after four weeks of treatment. The treatment was generally well tolerated
Conclusion: Sofosbuvir [Zoval] is effective and well tolerated in combination with ribavirin in HCV infected patients
ABSTRACT
Background: Ninety-five millions of Pakistan's 161 million people, roughly 60% of Pakistan's population live in malaria endemic regions. Despite a well-established malaria control programme, 500,000 malaria infections and 50,000 malaria-attributable deaths occur each year in Pakistan. In Pakistan 15% population lives in high transmission area, 84% in low transmission and 1% in malaria free area, with 64% vivax and 36% Falciparum infections
Objective: The objective of this study was to assess the therapeutic efficacy and safety of Dihydroartemisinin- piperaquine [DP] for the treatment of uncomplicated Plasmodium vivax malaria in subjects
Methods: Its an observational study, conducted at Outpatient Department of Liaquat University Hospital Hyderabad, from December 2012 to December 2013. World Health Organization [WHO] standard protocol for efficacy studies [open-labelled clinical trial] was followed. The subjects with fever or history of fever for 48 hours aged between 6 months to 15 years with microscopically confirmed uncomplicated P. vivax infection were included. Total 109 patients fulfilled the inclusion criteria. Out of 109 patients, 103 had completed the study. Patients were treated with Dihydroartemisinin-piperaquine over three days. Clinical and parasitological parameters were monitored over a 42-days follow-up period to evaluate drug therapeutic efficacy
Results: Adequate clinical and parasitological response of treatment [ACPR] for Dihydroartemisininpiperaquine [DP] was seen in 102/103 [99.02%] patients, no early or late clinical failure was seen while late parasitological failure was seen on 21[st] day in one patient. No adverse events were reported
Conclusion: Dihydroartemisinin-piperaquine is safe and effective treatment option for uncomplicated vivax malaria
ABSTRACT
Objective: The objective of the study is to find out, the levels of thyroid hormones in serum of the patients having decompensate cirrhosis and to determine the frequency of signs and symptoms of thyroid dysfunctions in such patients. Study design: Prospective descriptive study. Setting: All medical wards of Civil Hospital and Ojha campus, Dow University of Health Sciences, Karachi, Pakistan. Period: May 2013 to January 2015
Methodology: 76 patients having decompensated liver cirrhosis with various presentations, which were fulfilling the inclusion and exclusion criteria and were admitted in medical wards during the study period, were included in this study. Detailed history and examination of each case was performed. Thyroid hormone levels were performed along with other relative laboratory investigations and the results were obtained
Results: Out of 76 patients 58 patients had low serum T3 levels, whereas 18 had normal T3 levels. 65 patients had normal T4 levels and 11 had low serum T4 levels. The TSH levels were found normal in 74 patients and two patients had raised TSH levels
Conclusion: It is concluded that T3 levels is low in cirrhotic patients but at the same time T4 and TSH levels remains normal in majority of cases and the patients remain euthyroid. As far as the clinical scenario is concern, no significance was found in the frequency of sign and symptoms of thyroid dysfunction. Most of the patients did not show signs and symptoms of hyper and hypothyroids
Subject(s)
Humans , Male , Middle Aged , Female , Adult , Aged , Thyroid Hormones/blood , Prospective StudiesABSTRACT
Colonoscopy is one of the most important modalities to investigate complaints related to lower gastrointestinal tract. Terminal ileum is an essential part of the complete colonoscopic examination. Objectives: To observe the diagnostic yield of ileoscopy in patients undergoing colonoscopy. Design: Retrospective and observational study. Period: January 2010 to May 2014. Setting: Liaquat National Hospital and Medical College. Patients and methods: Patients undergoing colonoscopy fulfilling inclusion and exclusion criteria were enrolled. Terminal ileum was examined and biopsies taken if abnormality present. Statistical analysis was done by SPSS- 18. Result: A total of 1296 patients were included, 884 [68.2%] were male and 412 [31.8%] were female. Age ranged from 15-90 years. The commonest indication was bleeding per rectum [35.6%].1133[87.4%] patients had normal mucosaand163 [12.6%] had abnormal mucosa on ileoscopy. Of these 163 patients, 68 had ulcers, 56 had inflammation, 29 had nodular mucosaand10 had polyp. Histopathological examination showed non-specific inflammation in 139 patients; granulomatous inflammation in 7; reactive lymphoid hyperplasia in 8; 3 had normal result; biopsies were not taken in remaining 6 patients. By using chi-square test we found a significant statistical relationship between macroscopic abnormality of terminal ileum mucosaandage of patients, weight loss, chronic diarrhoea, and abdominal pain. On logistic regression, age group, chronic diarrhoeaandweight loss retained strong relationship with macroscopic abnormality of terminal ileum mucosa. Conclusions: Though a large number of patients [12.6%] had abnormal terminal ileum mucosa, histopathological analysis did notshow any significant yield of ileoscopy. Terminal ileal abnormality was more common in young and middle aged patients and in patients presenting primarily with chronic diarrhoeaandweight loss.
ABSTRACT
Objectives: To observe the frequency of QTc [corrected QT] interval prolongation in patients with chronic liver disease in our population
Study design: A cross-sectional analytical study
Place and duration: Department of Gastroenterology, Liaquat National Hospital and Medical College, Karachi from May 2009 to October 2009
Methodology: A non- probability, purposive sampling is used in already diagnosed cirrhotic patients. Patients between 25-70 years were included. These patients were divided into three groups according to their Child-Pugh [C.P.] classification [class A, class B and class C]. An electrocardiogram [ECG] of all patients was obtained and QT intervals corrected for heart rate [QTc] were calculated. Analysis of data was done by SPSS 17
Results: 121 cirrhotic patients were inducted in this study. 10 patients belonged to C.P. class A, 49 to C.P. class B, and 62 to C.P. class C. Prolonged QTc interval was observed in 48 [39.7%] patients while in 73 [60.3%] patients QTc interval was normal. Occurrence of prolonged QTc interval was greater in C.P. class-C [50%] followed by C.P. class-B [30.6%], p value 0.045 and 0.016 respectively
Conclusion: Significant number of cirrhotic patients had prolonged QTc interval and this prolongation of QTc interval was directly associated with more advanced liver disease
ABSTRACT
Objective: To discover the frequency and presence of multiple antimicrobial resistant strains of Pseudomonas aeruginosa [P.aeruginosa] in patients with Post tuberculosis bronchiectasis in Baluchistan
Design: A prospective descriptive study
Place and duration: this study was done in Pulmonology and tuberculosis outpatient department [OPD] of Fatimah Jinnah Chest Hospital and Rehan Hospital Quetta Pakistan from 1st October 2011 to 1st April 2012
Methodology: The samples were obtained from post tuberculosis patients [n=60, Age = 40+ years] suspected of bronchiectasis who were subjected to spirometry test, Mueller Hinton sensitivity testing, oxidase test and disk-diffusion method to find out frequency and multiple drug resistance of P. aeruginosa
Results: Our results confirmed the association of chronic P. aeruginosa infection with poor lung function. It is not clear whether P. aeruginosa caused the accelerated decline in lung function or it was just a marker of those whose lung function was already declining rapidly. The antibiotic susceptibility testing confirmed the presence of resistant strains of the P. aeruginosa most of which were mucoid strains. It proved that a single antibiotic therapy is not a good treatment for patients with P. aeruginosa infection in airways
Conclusion: Bronchiectasis is more frequently encountered in middle-aged and elderly persons and resistant strains of P. aeruginosa are highly prevalent in these patients
ABSTRACT
A Cross sectional study conducted in Cardiology Unit, Hayatabad Medical Complex from August 2011 to February 2012. In a total of 250 patients with non ST elevation MI were enrolled in study. Neutrophil to lymphocyte ratio [NLR] was determined. Those with high NLR were followed over two week period to detect in hospital mortality; Atrial Fibrillation and ST segment Deviation. Association of cellular response with the incidence of post-MI mortality/complications was assessed by multiple logistic regression analyses. There were 250 patients comprising of 154 [61.60%] males and 96 [38.40%] females. The overall mean age was 51.57 +/- 12.5 years. The frequency of high neutrophil to lymphocyte ratio was present in 78 [31.20%] patients. The In hospital mortality and atrial fibrillation rate was in 10.26% and 11.54% cases respectively while ST segment deviation was in 57.69% patients. Patients with Non ST Segment elevation Myocardial Infarction with high Neutrophil to lymphocyte ratio, is a good predictor of In hospital mortality, atrial fibrillation and ST segment deviation. Thus a single CBC analysis may help to identify Non- STEMI patients at risk for mortality and complications.
ABSTRACT
To observe the clinical and bio-chemical profile of patients having normal coronary angiogram following an abnormal stress test. This was a single center retrospective, descriptive study. Coronary angiograms done from July 2009 to December 2011 were retrieved and reviewed for normal coronary arteries. Clinical and bio-chemical profile of the patients having normal coronary angiogram was retrieved from hospital record. Patients, whose computerized data could not be retrieved from department database, were excluded from the study. Out of 8425 angiograms reviewed, 816[9.7%] were having normal coronary arteries. Mean age was 4 +/- 27.4 years. Females were 66.7%. Clinical and biochemical profile for normal coronary angiograms was as follows: smokers 59%, family history of premature coronary artery disease 41%, hyperlipidemia18.5% and hypertension 14%. Diabetes was present only in 2.1%. Among females: 11% were current users of oral contraceptives pills, 3.4% were post menopausal and 0.87% pregnant. Mean BMI was 25.4 +/- 5.2 and total cholesterol and triglyceride were 278 +/- 31mg/dl and 180 +/- 28mg/dl respectively. Normal coronary angiogram is infrequently observed in catheterization laboratories and mostly found in younger to middle aged females. Smoking is very common in such patients. Hyperlipidemia, hypertension, diabetes mellitus are not frequently present in these patients.
ABSTRACT
Objectives: To assess the validity /strength of clinical diagnosis of Malaria on the basis of IMNCI algorithm by slide microscopy [gold standard] and to compare the effectiveness of Rapid Diagnostic Test [RDT ]against slide microscopy
Methods: It is a descriptive cross sectional study of 6 month duration conducted at Pediatric Outpatient Department LUH Hyderabad from June-Dec. 2010. Sample of 400[the minimum required sample was 385 with malaria prevalence 5% [0.05] with margin of error of 3% [0.03, frequency vary from 2-8 % among different studies]] febrile children under 5 years classified as Suspected Clinical Malaria according to algorithm of IMNCI were included; The operational definition for Suspected Clinical Malaria was; fever for more than 2 days with no runny nose, no measel rash and no other cause of fever. Hyderabad was considered as low risk area. Rapid diagnostic test [RDT] and slide microscopy were done, and only confirmed cases were treated according to current guidelines given by National Malaria Program/updated IMNCI
Results: Total 2000 patients under 5 years presented with fever and were evaluated. From 2000 cases 20% [400] were diagnosed as suspected clinical Malaria according to IMNCI algorithm; and only 40 cases [10%] have shown positive results for malaria parasite on slide microscopy and 38 cases on RDT. Regarding the plasmodium species 70% were vivax and 30% were falciparum. As regards the effectiveness, RDT has shown 95% sensitivity for the detection of plasmodium antigens in the febrile clinically suspected cases of malaria
Conclusion: Prompt and accurate diagnosis of malaria is needed for implementation of appropriate treatment to reduce unnecessary anti-malarial prescription. RDT is as effective as slide microscopy for the diagnosis of malaria especially in resource poor countries
ABSTRACT
This study involves the design and characterization of Nateglinide [NAT] microspheres to enhance patient compliance. Ionic gelation technique was used to prepare Nateglinide Microspheres by using rate controlling polymers Carbopol-940 and Hydroxypropylmethyl cellulose [HPMC]. Shape and surface were evaluated with Scanning electron microscopy [SEM]. Percentage Yield, Particle size analysis, Encapsulating Efficiency, Micromeritic analysis, Fourier Transform Infra-Red Spectroscopy [FTIR], Differential Scanning Colorimetry [DSC] were done for characterization of Microspheres. Drug release studies were performed at pH 1.2 and 7.2 using USP dissolution type-2 apparatus and release rates were analyzed by the application of different pharmacokinetic models. The size of microspheres was found to be varied from 781 Micro m to 853 Micro m. Rheological studies proved excellent flow behavior while percentage yield was found to be varied from 72% to 79%. Absence of drug-polymers interactions was confirmed from FTIR and DSC results. The microspheres prepared with sodium alginate showed cracks while microspheres obtained from blend of Carbopol-940 plus sodium alginate were smooth and spherical. Maximum entrapment efficiency [71.4%] was achieved for Microspheres with Carbopol-940. The greater retardation in drug release was observed for microspheres containing Carbopol-940 and release pattern followed Higuchi kinetics model and negligible drug release was observed at pH 1.2
Subject(s)
Phenylalanine/analogs & derivatives , Microspheres , Acrylic Resins , Polymers , Methylcellulose/analogs & derivativesABSTRACT
To determine the frequency of H. pylori infection in dyspeptic patients undergoing endoscopy at a tertiary care center in Karachi. Patients undergoing endoscopy at Liaquat National Hospital, Karachi. Cross sectional descriptive study. Department of Gastroenterology, Liaquat National Hospital, Karachi. May 2008-October 2008. All adult patients with symptoms of dyspepsia for more than 1 month duration were included. Patients with upper gastrointestinal bleed, anemia or weight loss were excluded. Upper gastrointestinal endoscopy was performed in all patients and biopsy specimens two each from antrum and body and one from fundus were taken for histology. A total of 123 dyspeptic patients were included in the study. 76 [61.8%] patients were males and 47 [38.2%] were females. H pylori was detected in mucosa of 49 [39.8%] patients. The mean age of the patients was 41.41 +/- 13.15 Years [95%CI; 39.06 to 43.75]. Rate of H.pylori infection was not found statistical significant with age, gender, duration of symptoms and BMI. The prevalence of H pylori infection in dyspeptic patients was lower than reported in previous studies from other centers in Pakistan. Other environmental factors should be evaluated in every patient especially who is negative for H. pylori in our setup
ABSTRACT
Bouveret's syndrome is defined as gastric outlet obstruction caused by duodenal impaction of a large gallstone which passes into the duodenal bulb through a cholecystogastric or cholecystoduodenal fistula. This is a report of a 62 years old female who presented with complaint of persistent vomiting and upper abdominal pain for the last 5 days. Ultrasound abdomen was suggestive of pneumobilia. CT scan of upper abdomen showed cholecystoduodenal fistula and complete obstruction of third part of duodenum by a large stone, which was reported as Bouveret's syndrome. She underwent emergency gastroscopy. The stone was retrieved by Dormia basket, crushed with lithotripter and extracted endoscopically. Complete intestinal obstruction was relieved endoscopically
ABSTRACT
N-butyl-2-cyanoacrylate is widely used to sclerose bleeding gastric varices. We report the case of a 65-year-old lady, known case of cirrhosis secondary to hepatitis C infection, who presented to the emergency department with coffee ground vomiting and melena for four days. Gastroscopy showed non-bleeding small esophageal varices, mild portal hypertensive gastropathy and a large gastric fundal varix. Injection sclerotherapy was completed successfully and haemostasis was secured. During the procedure, she was hemodynamically stable with an oxygen saturation of 98%. Immediately after the procedure, she went into cardiopulmonary arrest; cardiopulmonary resuscitation [CPR] was started, but she could not be revived. A provisional diagnosis of pulmonary embolism was made. X-ray chest showed linear hyperdense shadows in both pulmonary arteries and in some of their branches, which were not seen on pre-procedural chest X-ray. The patient died of massive pulmonary embolism as confirmed on X-ray chest
ABSTRACT
To determine the frequency of factors leading to post endoscopic retrograde cholangiopancreatography [ERCP] pancreatitis. Case series. Department of Gastroenterology, Liaquat National Hospital, Karachi, from November 2007 to October 2008. Fifty [50] patients of diagnosed cases of post-ERCP pancreatitis were included in this study. The collected data included age, gender, previous post-ERCP pancreatitis, recurrent pancreatitis, recurrent abdominal pain, number of attempts of common bile duct [CBD] cannulation, difficult CBD cannulation, precut sphincterotomy, biliary sphincterotomy, pancreatic duct contrast injections, primary diagnosis, device used, therapeutic procedure undertaken and the pancreatic enzymes level. Results were described as frequency percentages. Out of 50 patients, 32 [64%] were females. The average age of the patients was 52.23 +/- 13.4 years. Frequency of common factors regarding post-ERCP pancreatitis were age 2 60, [n = 38, 76%] patients, female gender [n = 32, 64%], precut sphincterotomy [n = 34, 68%], pancreatic duct contrast injections [n = 27, 54%], biliary sphincterotomy [n = 25, 50%]. Higher number of attempts of CBD cannulation and difficult CBD cannulation were recognized as factors for post ERCP pancreatitis. Other factors like previous history, post-ERCP pancreatitis, recurrent pancreatitis, and recurrent abdominal pain were not found in this study. Age, female gender, precut papillotomy, pancreatic duct contrast injections and biliary sphincterotomy were common factors for post-ERCP pancreatitis. Risk stratification will allow endoscopists to better identify patients who are at risk and permit detailed informed consent in high-risk groups or to adapt the measures to prevent the complications and reduce the risk related with the procedure
Subject(s)
Humans , Male , Female , PancreatitisABSTRACT
Anticoagulant effect of clopidogrel is of utmost importance in coronary artery disease, especially in prevention of coronary stent thrombosis. Recently, many new local brands of clopidogrel have been launched, with unknown efficacy. This study was conducted with the aim to compare two locally prepared clopidogrel brands, in terms of the effect of a loading dose of 600 mg on inhibition of platelet aggregation in patients with coronary artery disease. This was a double blind randomised study. Sample population consisting of 35 patients, were admitted at Lady Reading Hospital, Peshawar, for the management of coronary artery disease. Baseline platelet aggregation of all these patients was measured. These patients were divided in two groups randomly. Group-A consisting of 18 patients was given brand 'A' clopidogrel 600 mg, while Group-B consisting of 17 patients was give brand 'B' of clopidogrel 600 mg. The platelet aggregation of both groups was then measured at baseline, and at 2, 4, and 6 hours after taking the loading dose of 600 mg. Platelet aggregation time at baseline in Group-A was 2.61 +/- 2.28 sec. and in Group-B it was 2.24 +/- 1.52 sec. [p=0.57]. After 2 hours of clopidogrel administration in Group-A the platelet aggregation time was 1.44 +/- 1.58 sec. and in Group-B it was 1.53 +/- 1.107 sec. [p=0.85]. Platelet aggregation time after 4 hours in Group-A was 0.28 +/- 0.57 sec. and in Group-B 1.06 +/- 1.03 sec. [p=0.009], and after 6 hours it was 0.00 +/- 0.00 sec. in Group-A and in Group-B it was 0.59 +/- 0.71 sec. [p=0.001]. The two brands of clopidogrel had a significant difference in their effect on inhibition of platelet aggregation. Different brands of clopidogrel may not be equally effective
Subject(s)
Humans , Female , Male , Platelet Aggregation Inhibitors , Coronary Artery Disease , Double-Blind Method , Randomized Controlled Trials as TopicABSTRACT
Renal artery stenosis [RAS] is a common finding in patients undergoing coronary angiography. We designed this study to look for the frequency and any predictors of renal artery stenosis in patients with coronary artery disease [CAD]. A total of 201 consecutive patients with CAD confirmed by coronary angiography underwent an abdominal aortogram in the same sitting to screen for RAS. Patient demographics and co-morbidities were analysed for any association with RAS. Forty-one of the patients were female [20.4%]; ninety patients were hypertensive [44.8%]; 49 patients [24.4%] were smokers; 19 patients [9.5%] had renal insufficiency; 88 patients [43.8%] had high cholesterol levels; 44 patients [21.9%] were diabetic. Thirty-two patients [15.9%] had single coronary artery disease, 59 patients [29.4%] had two vessel disease, and 110 patients [54.7%] had three vessel disease. Significant renal artery stenosis [>/= 0.50% stenosis] was present in 26 patients [12.9%]. Among the variables studied, only female gender was found to be associated with a higher frequency of renal artery stenosis [24.39% vs 10.0%, p=0.01]. The frequency of renal artery stenosis in patients with coronary artery disease is 12.9%. Female gender is associated with a higher frequency of renal artery stenosis in patients with CAD
Subject(s)
Humans , Female , Male , Coronary Artery Disease/pathology , Coronary AngiographyABSTRACT
To find out the frequency of complications of acute appendicitis. A retrospective study was conducted at surgical unit-I and III, Chandka Medical College Hospital, Larkana. Case records of patients who were admitted with complications of appendicitis from June 2004 to May 2007 were examined and data analysed. Most common complications of appendicitis were appendicular mass [38.3%] followed by appendicular perforation and peritonitis [37.5%], appendicular abscess [10%], gangrene of appendix [11.6%] and intestinal obstruction [2.5%]. Majority [66.6%] of the cases were operated while 33.3% were treated by conservative measures. Appendicular mass and perforation were the main complications of untreated acute appendicitis. Complications of appendicitis usually result due to delay in diagnosis and treatment