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The Association Between Asymptomatic and Mild Neurocognitive Impairment and Adherence to Antiretroviral Therapy Amongst People Living With Hiv

Thesis Info

Author

Violet Maloba Awori

Department

Internal Medicine (East Africa)

Program

MMed

Institute

Aga Khan University

Institute Type

Private

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2016

Thesis Completion Status

Completed

Subject

Medicine

Language

English

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676728068273

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Background: HIV disease is associated with neurocognitive impairment which is one of the neurological complications of the viral infection. The spectrum of HIV Associated neurocognitive impairment has significantly changed since the advent of ART. The inclusion of the asymptomatic but cognitively impaired population of patients has changed the dynamics of this population, and requires further research to identify the impact it has on the progression of the disease as well as on any other aspects. Poor adherence to ART is one of the main causes of treatment failure and studies done previously point towards the milder forms of Neurocognitive Impairment as being a cause of poor adherence, among other aspects. Primary Objective: To assess the association between the milder forms of neurocognitive impairment and adherence to ART. Methods: The study was a cross-sectional survey, with consecutive sampling, with a total sample size of 218 patients. An association was sought between cognitive status and adherence as measured by objective means, self-reported means and last viral load value as a surrogate marker. The study utilised quantitative primary data on pre-defined baseline characteristics, neurocognitive assessment by MOCA, instrumental activities of daily living by Lawton score and objective and subjective adherence measures by medication possession ratio (MPR) and simplified medication adherence questionnaire (SMAQ) respectively. Univariate and bivariate analysis was conducted to determine the strengths of association between various predictor and the outcome variables. Results: A final sample size of 218 was selected out of all those eligible (500 patients). All study participants underwent a neurocognitive assessment, which revealed 69% minor neurocognitive impairment while 31% had no neurocognitive impairment. No patient was identified with HIV associated dementia on screening. Secondly, all study participants underwent adherence assessment which revealed optimal adherent rates of 66% and 77% by objective (by MPR) and subjective (SMAQ) measures respectively. There were no statistically significant differences in the baseline characteristics (age, gender, education, marital status, living arrangements, employment status, level of income) between the group of participants with cognitive impairment and those without impairment (p-value > 0.05). Similarly, when the same group were compared on characteristics related to their HIV diagnosis and treatment, no statistically significant differences were observed (p-value > 0.05). Discussion: Even though the rate of cognitive impairment in this study was high, it corresponds to some of the studies earlier carried out (CHARTER study = 53%), the majority of which were asymptomatic and Mild Cognitive Disorders, while only
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ارشاد ڈیروی تے عصری شعور

ارشادڈیروی تے عصری شعور

اجوکے سمے دیاں دیاں مشہور اصناف سخن وچوں غزل اک اجیہی صنف سخن اے ، جس دے وچ سب توں ود ھ طبع آزمائی ہو رہی اے ۔ایس صنف وچ نویں نویں تجربے ہو رہے نیں تے نویں سرنانویاں نوںایس صنف راہیں بیان کیتا جا رھا اے ۔غزل دا ہر شعر اپنی تھاں اک مکمل اکائی ہو ندا اے ۔۔اوہدے وچ شاعر اپنی فکر تخیل یاں جذبہ مکمل طور تے بیان کریندا اے ۔ایس پاروں کچھ نقاداں نے ایس نوں ’’منتشر الخیال ‘‘صنف آکھیا اے ۔(۱)کیوں جے ایہدے وچ نظم ونگوں خیالا ں دا ربط تے تسلسل نہیں ہو ندا۔ایس دے باوجود غزل دے سارے شعر قافیہ تے ردیف دے داخلی دھاگے نال اک دوجے نال جڑے ہو ندے نیں ۔ڈاکٹر وزیر آغا دا خیال اے :

’’غزل کا ہر شعر ایک ایسا جزو ہے جو غزل کا حصہ ہو نے کے باوجود اس سے جد ا بھی ہے ۔ہر شعر ایک الگ حیثیت کا حامل ہے لیکن اس کے باوجود وصف غزل کے دھاگے سے منسلک بھی ہیں ۔‘‘(۲)

غزل واسطے سرنانویاں دی کوئی پابندی نہیں ہو ندی ۔ایس لئی ایہدے وچ حسن تے عشق ،جوانی تے بڑھاپا ،زمین تے آسمان ،سماج تے معاشرہ ،ریاست تے سیاست ،علم تے فن یعنی ہر قسم دے خیالات وکھو وکھ شعر اں وچ بیان کیتے جا سکدے نیں ۔پر اوہناں ساریا نوں ایک دوجے نال جوڑ کے رکھن لئی اک مخصوص داخلی رنگ،مخصوص جذبے تے احساس دی لوڑ اے ۔انج تد ای ہو سکداے جدوں شاعر حیاتی دے سبھے خارجی منظراں نو ں اپنی ذات تے فکر دا حصہ بنا لوے ۔اوہناں نوں شعراں دے روپ وچ ڈھالدیاں ہویاں اوہ اپنی ذات توں وکھریاں نہ کرے ۔سگوں اپنی ہڈو ورتی بنا کے پیش کرے ۔شاعر غزل...

Aristotle’s Virtue of Justice as an Ethical Solution to Political Corruption: Analysis and Reflection

This paper attempts to discuss Aristotle’s concept of justice as an ethical solution to political corruption. The goal of this paper is to present corruption as a form of injustice that deprives the majority from a common good. This paper is very important because it provides ethical solution to grand corruption whereby unscrupulous individuals divert funds meant for development of the entire society into private hands. Due to grand corruption the poor masses are deprived of quality basic needs. The paper focuses on corruption as an immoral act through the lens of Aristotle’s ethical and political insights. The virtue of justice in Aristotle’s ethical and political works are spelled out. The methodology used in this paper is analytical and applied. It is analytical because it analyses Aristotle’s understanding of virtue of justice in his moral theory especially in his book entitled Nicomachean Ethics and justice in his political theory. Finally, the paper makes subsequent applications of Aristotle’s virtue of justice in the realm of ethical solutions to the problem of corruption.

Biological, Immunological and Molecular Studies on Caprine Mycoplasma in Balochistan

Mycoplasma species belong to the class Mollicutes, and are well known for inflicting respiratory diseases in animals including goats. Respiratory mycoplasmosis particularly caprine pleuropneumonia or contagious caprine pleuropneumonia (CCPP) is well known to inflict significant economic losses to goat production in many parts of the world including Balochistan, Pakistan. Mycoplasma diseases especially respiratory problems are characterized with fever, nasal discharge, cough, dyspnoea, pleuropneumonia with higher rates of morbidity and mortality. Caprine pleuropneumonia and associated respiratory problems caused by members of the Mycoplasma mycoides cluster members particularly with Mycoplasma mycoides subspecies mycoides large colony (MmmLC), Mycoplasma mycoides subspecies capri (Mmc), and Mycoplasma capricolum subspecies capripneumoniae (Mccp) have been known since long in Balochistan, Pakistan. The studies on the prevalence, isolation, identification, sero-molecular diagnosis, and immuno-prophylactic control for the frequently reported mycoplasma diseases are not well carried out and addressed. The clinico-bacteriological investigation for the isolation and characterization of Mycoplasma species from the nasal swabs of the randomly selected goats from fifteen districts of Balochistan has been found with varying proportions of clinical symptoms among goats with highest (27.2%) for nasal discharge and least (7.2%) for diarrhea. Overall 3.7% prevalence of Mycoplasma species by nasal swab cultures was observed in goats. Highest isolation (78.1%) was observed for single Mycoplasma species than the concurrent isolation (21.9%) of MmmLC with other Mycoplasma species. The highest rate of isolation was observed for Mmc (16%), followed by Mcc (15.9%), Mycoplasma arginini (13.7%) and concurrent infection of MmmLC with M.arginini organisms (12.2 %). Surprisingly Mycoplasma putrefacience (Mp) as 9.2 percent was isolated from the nasal swabs of goats. Statistically highest prevalence of mycoplasma species in goats by the nasal swab culture was observed in Loralai district followed by Pishin, and Quetta as compared to Nasirabad district. The gross-pathologic and bacteriological study for the lungs collected from goats slaughtered at locally organized butcher shops in districts of Balochistan has shown 11% prevalence of pneumonic lesion among goats. Statistically significant difference in prevalence of pneumonic lesions among goats between the districts was observed. Of the pneumonic lesions, highest frequency was noticed for broncho-pneumonia (31.9%) followed by fibrinous-pneumonia (23.5%), while the lowest frequency was noted for congested lungs (7.0%). Overall mycoplasmas were isolated from 4.7% of the lung samples from goats. The highest rate of isolation was 43.6% for MmmLC, 18.5% for Mmc, and 10.9% for Mcc, while lowest prevalence of 1.9% was observed for M. arginini. Statistically significant difference for the isolation of mycoplasma species between the districts was found. The clinico-pathologic and bacteriological study for the pleuropneumonia suspected goats (n=210) from fifteen districts of Balochistan has shown highest frequency of clinical symptoms for nasal discharge (82.4%) followed by cough (47.6%), anorexia (26.7%), pyrexia (20.5%), dyspnoea (19%) and swollen fore-limb joints (15.2%). The pneumonic lesions were present as 87.1% and statistically non-significant difference was observed in the occurrence of pneumonic lesions between the districts. Highest frequency of gross lesions was observed for pneumonia (87.1%), followed by lung adhesions (27.1%), and hydrothorax (8.6%). Pneumonic lesions further showed highest frequency for lobar pneumonia (29.5%), followed by fibrinous pneumonia (27.9%), and broncho-pneumonia (20.2%). Mycoplasma were positive in 31% of the samples (n=1890) from different body sites of the pleuropneumonia suspected goats. Overall, 34.23% mycoplasma isolates were recovered and characterized. The highest isolation was observed for MmmLC (43.74%), followed by Mcc (13.45%), Mmc (11.59%), and Mycoplasma arginini (7.11%). Of the pleuropneumonia suspected goats, the highest isolation of mycoplasmas was observed from the lung tissues (27.1%), followed by nose (25.3%), while, the lowest isolation was observed from intestine (1.7%). Significant difference in the isolation of mycoplasmas from different body sites of the goats was observed. The odds ratio value analysis showed higher isolation of mycoplasmas from the lung tissues followed by nose, trachea, liver, spleen, and fore- limbs joint fluid than the intestine samples. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and denaturing gradient gel electrophoresis (DGGE) were used for the identification of Mycoplasma species isolated from goats in Balochistan. Of the mycoplasma isolates (n=1120) previously characterized by the classical biochemical and growth inhibition tests, highest number (78%) was identified by the Mycoplasma mycoides cluster PCR, followed by Mycoplasma mycoides sub-cluster PCR (63.3%), and Mp PCR (6.3%), while none of the isolate was identified as Mccp by the Mccp-specific PCR. Among the mycoplasma isolates highest percentage was observed for MmmLC (44.8%), followed by Mmc (18.5%), and Mcc (14.7%), while the lowest was found for Acholeplasma (2.5%), followed by Mp (6.3%), and Mycoplasma arginini (13.1%). The Mycoplasma mycoides sub-cluster PCR results for MmmLC/Mmc were also validated by specific RFLP. Of the 20 mycoplasma isolates, 8 (44.4%) were specifically identified as MmmLC, 10 (55.5%) for MmmLC with unknown type of microorganism profile, while two of the mycoplasma isolates could not be analyzed by DGGE at Veterinary Laboratories Agencies (VLA), Weybridge, United Kingdom. Whole genomic DNA was extracted directly from 5760 nasal swabs (randomly selected field goats), 4522 lung tissues (goats slaughtered in butcher shops) and 210 lung tissues (pleuropneumonia suspected goats) from the goats from fifteen districts of Balochistan to highlight the prevalence of Mycoplasma species in goats using PCR reactions. The PCR results for the nasal swabs samples showed highest prevalence for Mycoplasma mycoides cluster (6.6%), followed by Mycoplasma mycoides sub-cluster (5.6%), and Mcc (1%), whereas the lowest prevalence was noted for Mp (0.7%). The PCR results for the lung tissue samples (goats slaughtered in butcher shops) has shown highest prevalence for Mycoplasma mycoides cluster (11.7%), followed by Mycoplasma mycoides sub-cluster (10.2%), and Mcc (1.6%), while the lowest prevalence was observed for Mp (0.8%). The lung samples (pleuropneumonia suspected goats) showed highest prevalence for Mycoplasma mycoides cluster (76.7%), followed by Mycoplasma mycoides sub-cluster (56.2%), and Mcc (19%), while the lowest prevalence for Mp (5.2%) was observed. Statistically highly significant difference was observed for the prevalence of Mycoplasma species in all the samples by PCRs. The PCR results for the Mycoplasma mycoides cluster and Mccp organisms were validated by specific RFLP for MmmLC/Mmc and Mccp organisms. Only 1.4% prevalence of Mccp was observed in lung tissue samples from pleuropneumonia suspected goats by the Mccp- specific PCR. Latex agglutination test (LAT) and indirect haemaggluitination (IHA) assay were standardized and used to highlight the sero-prevalence of MmmLC infection in goats in Quetta, Pishin and Loralai districts of Balochistan. Of the 50 serum samples from the healthy goats (negative for Mycoplasma mycoides cluster and Mp by PCRs and mycoplasma culture), 90% and 74% specificity was observed by LAT and IHA (titer <1:64 considered negative titer) respectively with statistically significant difference. Further, of the 59 serum samples from the pleuropneumonia suspected goats (positive for MmmLC by the PCRs and mycoplasma culture), 92% and 70% sensitivity was calculated by LAT and IHA (the cut-off value for the antibody titer ≥1:64 taken as positive) respectively with statistically significant difference. IHA and LAT has shown 18.5%, 14.3%, 13.5% and 21.9%, 18% 16.1% sero-prevalence to MmmLC in goats from Quetta, Pishin and Loralai districts in Balochistan respectively. Statistically non-significant difference by IHA, and LAT was observed in the sero-prevalence among the three districts. Statistically significant difference in the overall sero-prevalence to MmmLC by IHA (15.5%) and LAT (18.7%) was observed in three districts in Balochistan. Mycoplasma species such as MmmLC, Mmc, Mcc, Mp, Mycoplasma arginini (Marg) isolated from the pleuropneumonia suspected goats from districts of Balochistan and Mmc (PG- 3, vaccinal strain) were used by intra-nasal spray and intra-tracheal routes to reproduce experimental mycoplasma disease in goats. Only goats in groups A and B infected with MmmLC by nasal spray and intra-tracheal routes has shown moderate to severe respiratory disease characterized with pyrexia (up to 41.5oC), nasal discharge, cough, swollen and painful fore-limb joints and lameness with 100% mortality before the end of experiment. Gross-pathology revealed lung congestion, fibrinous pleuropneumonia, lung adhesions, and hydrothorax in the necropsied goats. A low grade respiratory disease characterized with slight nasal discharge and slight lameness was seen in few goats infected with Mmc, Mcc, and Mp field isolates with no mortality. The Mmc (PG-3, vaccinal strain) was also found ineffective in causing a clinical respiratory disease in the experimental goats. Of the total samples (n=420) from different body sites of the experimentally infected goats (n=42) with Mycoplasma species from 14 groups (A-N), 16.2 % mycoplasma isolates were re-isolated. Of these 79.4% (MmmLC), 4.4% (for each of Mmc and Mp), 5.9% for each of Mcc and M.arginini) were identified by the classical biochemical, growth inhibition tests and Mycoplasma mycoides cluster, Mycoplasma mycoides sub-cluster, and Mp specific PCR tests. Sero-conversion against MmmLC was seen only in goats from group A by LAT and IHA. Different concentrations of formalin and saponin inactivated MmmLC vaccines containing 2, 1, 0.5, 0.25, 0.125, 0.06 and 0.03 mg/ml protein and adjuvated with saponin (1mg/ml) or aluminum hydroxide gel (5mg/ml) were prepared, used and evaluated for efficacy in 17 groups of goats (5 goats/group). Saponin and formalin were found suitably mycoplasmacidal in 0.5 mg/ml and 0.125% concentrations at 37oC within 12 hours post-exposure respectively. Saponin is found with comparatively higher efficacy than aluminum hydroxide gel adjuvated MmmLC vaccines. Comparatively higher mean antibody titers up to (log2) of 9.5 for saponated vaccines as compared to (log2) of 6.2 for aluminum hydroxide gel based vaccine and (log2) of 4.2 for Mmc vaccine (CASVAB) were observed on 42 days post-vaccinations. The challenge and protection experiment also showed complete protection in mortality, clinical mycoplasma disease, and gross-pathological lesion only in goats for group nos. 1, 2, 3, and 4 inoculated with saponated MmmLC vaccine with 2, 1, 0.5 and 0.25 mg/ml protein for 3 weeks post-challenge period. There was a prompt and sharp increase in (log2) mean antibody titers for the MmmLC saponated vaccines as compared to the aluminum hydroxide gel based vaccines up to 3 weeks post-challenge. The antibody titers in saponated MmmLC vaccinated goats were seen with little decline but nonetheless were suitably maintained as compared to aluminum hydroxide gel based vaccines. Overall the studies carried out in this thesis have shown alarming status of MmmLC as compared to other isolated Mycoplasma species among goats. The vaccine prepared so far against MmmLC is found safe, immunogenic and protective in experimental goats but further needs trials in the field goats. Although Mccp the sole causative agent of CCPP was not isolated from the goats in Balochistan but its molecular detection by Mycoplasma mycoides cluster PCR and confirmation by Mccp-specific PCR-RFLP from the pleuropneumonia suspected goats from areas closer to Afghanistan is highly alarming and needs attempts to isolate the fastidious bacterium for further molecular epidemiological studies and preparation of an effective vaccine against CCPP, an OIE listed highly contagious and infectious disease of goats. It is anticipated that the research out comes presented in this thesis would greatly benefit the researchers, veterinarians and all those directly or indirectly involved in controlling the mycoplasma inflicted diseases." xml:lang="en_US