ASSESSMENT OF PRACTICE AT RETAIL PHARMACIES IN PAKISTAN: EXTENT OF COMPLIANCE WITH THE PREVAILING DRUG LAW OF PAKISTAN.

The main objective of this study was to assess the practice at retail pharmacies in Pakistan and to compare the same in rural and urban areas. The maintenance of pharmacy and drug inspectors' visit was also assessed. This cross sectional study was conducted in Abbottabad, Pakistan during October-November, 2012. A sample of 215 drug sellers or drug stores was selected by employing convenient sampling method. With a response rate of 91.6%, 197 drug sellers participated in this study. All the drug sellers were male. Overall, 35% (n = 197) of the drug sellers did not have any professional qualification. A majority of the drug sellers were involved in various malpractices like selling of medicines without prescription (80.7%), prescribing practice (60.9%), prescription intervention (62.4%) and selling of controlled substances (66%) without a license for selling it. These malpractices were significantly higher in rural area than that in urban area.

Comparative Efficacy of Intralesional Chloroquine With Intralesional Meglumine Antimoniate in the Treatment of Cutaneous Leishmaniasis.

BACKGROUND AND AIM: This comparative prospective study was conducted at the Department of Dermatology, Pak Emirates Military Hospital, Rawalpindi, from August 1, 2018, to January 31, 2019 (six months). This study aimed to compare the efficacy of intralesional chloroquine with intralesional meglumine antimoniate in the treatment of cutaneous leishmaniasis. MATERIALS AND METHODS: A total of 64 patients fulfilling the inclusion criteria reporting to the Department of Dermatology, Pak Emirates Military Hospital were included in this study. Informed consent was taken and demographic data including patients' hospital registration number, age, gender, and number of lesions were noted. The subjects were randomly assigned into two groups. In group A, intralesional chloroquine was injected two times per week, and in group B, intralesional meglumine antimoniate was injected two times per week. The efficacy of both treatments was noted after eight weeks of treatment. Frequency and percentages were computed for qualitative variables like gender and number of lesions. Mean±standard deviation was presented for quantitative variables like age. Analysis was done to compare the proportion of both groups. Chi-square test was applied to compare the efficacy of both groups, p≤0.05 was taken as significant. RESULTS: In this study, the mean age of patients was 29.69±08.95 years. There were 63 (98.44%) males and one (1.56%) female. In this study, efficacy was achieved in six (18.8%) patients in group A, while in 17 (53.1%) patients in group B. This difference was statistically significant, i.e., p=0.004. CONCLUSION: This study concluded that intralesional meglumine antimoniate is more effective in treating cutaneous leishmaniasis than intralesional chloroquine.

Real time and accelerated stability studies of Tetanus toxoid manufactured in public sector facilities of Pakistan.

Tetanus is an acute illness represented by comprehensive increased inflexibility and spastic spasms of skeletal muscles. The poor quality tetanus toxoid vaccine can raise the prevalence of neonatal tetanus. WHO has taken numerous steps to assist national regulatory authorities and vaccine manufacturers to ensure its quality and efficacy. It has formulated international principles for stability evaluation of each vaccine, which are available in the form of recommendations and guidelines. The aim of present study was to ensure the stability of tetanus vaccines produced by National Institute of Health, Islamabad, Pakistan by employing standardized methods to ensure constancy of tetanus toxoid at elevated temperature, if during storage/transportation cold chain may not be maintained in hot weather. A total of three batches filled during full-scale production were tested. All Stability studies determination were performed on final products stored at 2-8°C and elevated temperatures in conformance with the ICH Guideline of Stability Testing of Biological Products. These studies gave comparison between real time shelf-life stability and accelerated stability studies. The findings indicate long-term thermo stability and prove that this tetanus vaccine can remain efficient under setting of routine use when suggested measures for storage and handling are followed in true spirit.

Comparative analysis of the severity and progression of cutaneous leishmaniasis caused by Leishmania tropica in untreated and glucantime-treated patients.

Millions of people worldwide are affected by cutaneous leishmaniasis (CL), a disease that has a significant impact on morbidity and mortality. Understanding the immune responses responsible for tissue damage or the process of lesion healing plays a pivotal role in shaping optimal treatment strategies. In this study, we investigated immunological phenotypes for three groups: glucantime treated (n = 30) and untreated (n = 30) CL patients infected with Leishmania tropica (L. tropica), and healthy controls (n = 20). T-lymphocytes (CD4+ and CD8+), and B lymphocytes (CD14+ and CD19+) were isolated using antibody-conjugated microbeads and magnetic field isolation to achieve high purity. A higher significant difference was observed between T-lymphocytes (CD4+ and CD8+), and B-lymphocytes (CD14+ and CD19+) cells in CL-infected groups before and after treatment (p < 0.0001). When compared, there was also a significant difference among T-lymphocytes (CD4+ and CD8+), B lymphocytes (CD14+ and CD19+) p < 0.0001, p < 0.0005, and p < 0.0007, respectively between CL-infected individuals (before and after treatment) to controls. Our findings suggest that an increased proportion of these cells seen in treated patients may mediate healing, while it is also possible that they may contribute to tissue injury. Understanding the immune system and lesion size of CL can help develop immunotherapies and comprehend the evolution of this parasitic disease.

Multiparametric approach to assess the disease severity and progression of cutaneous leishmaniasis infection.

The pathophysiology of Cutaneous Leishmaniasis (CL), an infection caused by Leishmania tropica (L. tropica) and Leishmania major (L. major) is primarily determined by inflammation-mediated immune cells. The immune response mainly depends on cells and molecules related to T-cells that influence susceptibility and disease development. Understanding the immunological mechanisms that cause tissue injury or lesion healing is critical for developing appropriate treatment strategies. In the present study, T-cells profile and cell-free mitochondrial DNA (CF mt-DNA) were investigated in CL patients infected with L. tropica (n = 34) and L. major (n = 2) and compared with non-infected healthy controls (n = 20). There was a significant (p<0.0001) difference between CD4+ T-cells among L. tropica and L. major CL-infected groups as compared to control while no significant difference (p = 0.8597) was found in the percentages of CD8+ T-cells. When L. tropica and L. major CL-infected individuals were compared to controls, the levels of IL-4 and expression of CF mt-DNA were significantly higher (p<0.0001). Higher levels of CF mt-DNA were detected in CL patients, irrespective of the infective Leishmania species. We proposed that the levels of CF mt-DNA and IL-4 in CL-infected individuals can be used to determine the disease progression. A better understanding of these biomarkers and evaluation of the immune responses in CL patients might benefit the development of vaccines and immunotherapies.

Comparison Of Oral Dapsone With Intramuscular Meglumine Antimoniate In Cutaneous Leishmaniasis.

BACKGROUND: Many drugs are effective are used as second line treatment for cutaneous leishmaniasis. Dapsone therapy is tolerated well and cost effective. The aim of present study is to determine the efficacy of oral dapsone in comparison with intramuscular meglumine antimoniate in patients with cutaneous leishmaniasis and thus find out an effective second line treatment agent. METHODS: This randomized controlled trial was carried out at dermatology department, of tertiary care centre Rawalpindi, Pakistan from November 2017 to June 2018. Hundred biopsy proven patients of cutaneous leishmaniasis completed the study with 50 patients in two group. Group A received intramuscular meglumine antimoniate (15 mg/kg/day). Group B received oral dapsone2.5 mg /kg/body weight /day (200 mg per day). Efficacy of therapeutic response was noted at the end of treatment. Data was analyzed with statistical analysis program (IBM-SPSS V22). Chi-square test was applied to compare efficacy, p value of ≤0.05 was significant. Stratification of data with respect to age, gender, duration of disease, number of lesions and weight was done to see their effect on treatment efficacy. Post stratification chi-square test for both groups was applied (p≤0.05 considered significant). RESULTS: A total of 100 participants took part in the study. Duration of treatment (p-value <0.001) and the efficacy of the drugs (p-value=0.020) were significant. Meglumine antimoniate therapy group displayed a comparatively fast-paced recovery in (21- 40 days) whereas Dapsone group showed better recovery in (41-60 days) in their lesions. CONCLUSIONS: Dapsone is an effective treatment for cutaneous Leishmaniasis.

Paraneoplastic Addisonian pigmentation and acquired ichthyosis as presenting features of multiple myeloma.

Black brown hyperpigmentation of the mucosae, sunexposed skin, palmar creases and frictional sites (Addisonian pigmentation) is characteristic of Addison disease. However, it can also occur as a paraneoplastic manifestation of tumours like bronchogenic carcinoma. Acquired ichthyosis starts later in life and can also be a paraneoplastic presentation. We report a unique combination of paraneoplastic Addisonian pigmentation and acquired ichthyosis as presenting features in a patient with undiagnosed multiple myeloma. To the best of our knowledge this combination of paraneoplastic dermatosis has not been documented before in multiple myeloma. It is concluded that the presence of more than one suspicious dermatosis may be an indicator of being paraneoplastic requiring necessary work-up.

Constitutional and behavioral risk factors for chilblains: a case-control study from Pakistan.

OBJECTIVES: To study constitutional and behavioral risk factors for chilblains in patients at Abbottabad and Sialkot, Pakistan. METHODS: One hundred patients and matched controls completed a single-page, close-ended questionnaire which included demographic data and questions related to possible constitutional and behavioral risk factors for chilblains. Computer program SPSS-10 was used to manage and analyze the data. Risk factors were identified statistically by determining odds ratios and 95% confidence intervals using multivariate analysis. RESULTS: There were an equal number of male and female respondents in each group. Age of the patients and controls ranged from 2 to 80 years with a mean of 24.51 +/- 16.02. Twenty-six patients and 3 controls had a positive family history for chilblains (odds ratio = 9.33); 42 patients and 14 controls reported a history of constipation (odds ratio = 2.69); 32 patients and 8 controls had a history of either numbness or tingling of fingers or toes (odds ratio = 2.93); 55 patients and 45 controls led sedentary lifestyles (odds ratio = 1.27); 85 patients and 58 controls consumed a low number of cups of tea daily (odds ratio = 3.20); 65 patients and 29 controls frequently washed their hands and/or feet (odds ratio = 4.93); and 56 patients and 33 controls had occasional sun exposure during winter months (odds ratio = 2.08). CONCLUSION: Significant risk factors for the development of chilblains for people at Abbottabad and Sialkot included a history of chilblains in first-degree relatives, numbness and tingling sensations of fingers or toes, frequent hand or feet washing, and lower tea consumption during winter months.

Zinc deficiency in patients with persistent viral warts.

OBJECTIVE: To determine the association of low serum zinc levels with persistent, progressive or recurrent viral warts. STUDY DESIGN: A comparative study. PLACE AND DURATION OF STUDY: Dermatology outpatient department of Combined Military Hospital, Abbottabad in collaboration with Department of Chemical Pathology, Army Medical College, Rawalpindi, from June 2006 to May 2007. METHODOLOGY: Seventy five patients having warts of more than six months duration, more than 10 in number, who either not responded to or had recurrence after previous treatments for viral warts and not having other chronic dermatological or systemic illness were included in the study after informed consent. Seventy five age and gender matched healthy individuals were taken as control. Serum zinc analysis was carried out by atomic absorption spectrometry using Perkin elmen (USA) apparatus. Independent sample t-test was used to compare mean zinc levels in microgram/litre with significance at p < 0.05. RESULTS: Age of the patients as well as controls ranged from 12-65 years with a mean of 25.88 + 8.90 years. Serum zinc level was low in 42 (56%) patients and 24 (32%) controls (p=0.003). Among the patients, serum zinc level ranged from 695-1090 micro-gram/litre with a mean of 804.38 + 100.60, whereas the level ranged from 690-1100 microgram/litre with a mean of 836.17 + 91.04 among controls (p 0.044). CONCLUSION: Zinc deficiency is associated with persistent, progressive or recurrent viral warts in the studied patients. Randomized controlled trials with careful dose adjustment of oral zinc sulphate may be helpful to formulate guide lines to manage such patients.

Treatment of toxic epidermal necrolysis (TEN) with low dose intravenous immunoglobulin in child.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN, Lyell's disease) are severe, episodic, acute mucocutaneous reaction that may be caused by various factors particularly drugs. Treatment is primarily supportive care and there are no specific therapy regimens. Intravenous immunoglobulin (IVIG) has recently been shown to be a useful and safe therapy in paediatric patients with SJS/TEN, though no such case has so far been reported from Pakistan. The authors report the experience with low dose IVIG (0.1 g/kg/day for four consecutive days for treating a 3 years old boy with toxic epidermal necrolysis with favourable outcome without early complications.

Discriminative value of anorectal manometry in clinical practice.

Guidelines recommend anorectal manometry in patients with fecal incontinence and chronic constipation. However, limited evidence supports the utility of manometric testing. We retrospectively reviewed tracings obtained between November 2005 and May 2008. A total of 298 patients (86% women; average age 52 years) were included. The main indications were incontinence (51%) and constipation (42%). Patients suffering from incontinence were older and had lower resting and squeeze pressure compared to continent patients. However, the discriminative power of manometric pressure data was poor, with low sensitivity and specificity. An abnormal straining pattern suggesting dyssynergic defecation was seen in 43% of constipated patients compared to 13% of patients with fecal incontinence. A concordance between manometric patterns and the balloon expulsion test was seen in 72%. The low sensitivity and specificity of manometric parameters does not support the routine use of anorectal manometry in patients with defecation disorders.

Why dermatology patients are hospitalized? A study from Pakistan.

In most countries, there are no specified protocols or guidelines for admitting dermatology patients and admission criteria depend on assessment and sometimes the whim of the dermatologist. Although the severity and extent of the disease are the commonest reasons for hospitalizing dermatology patients, sometimes other factors also operate to provide comfort to the patient. This study was carried out to determine the reasons for hospitalizing patients on dermatology beds in secondary care hospitals of Pakistan. A questionnaire comprising patients' demographic data, diagnosis, specific reasons for hospitalization and length of hospital stay was sent to dermatologists of 10 secondary care hospitals in the country. The data received in response were processed and analyzed using the SPSS-10 computer program. A total of 310 patients were included in the study. Patient age ranged from 1 to 87, mean 28.87+/-12.32 years. The severity and extent of the disease (n=122; 39.3%), outpatient treatment failure (n=57; 18.4%) and need for further observation and/or investigations (n=51; 16.5%) were the most common reasons for hospitalizing these patients. Hospital stay of the patients ranged from 2 to 30, mean 9.82+/- 6.43 days. Scabies (n=56; 18.1%), chickenpox (n=52; 16.8%) and eczema (n=41; 13.2%) were the most common diagnoses.

A clinicopathological study of urethritis in males.

OBJECTIVE: To determine the etiology and frequency of different types of urethritis in adult males. STUDY DESIGN: A case series. PLACE AND DURATION OF STUDY: The Dermatology Department of PNS Shifa Hospital, Karachi, from June 2004 to December 2007. METHODOLOGY: One hundred male patients having complaints of urethral discharge and dysuria reporting in the skin OPD were included in the study. Patients who had received systemic treatment for their complaints and those who had other systemic infections were excluded. A detailed history including history of sexual contact was taken. Dermatological examination including examination of external genitalia was also performed. All these patients were subjected to complete physical examination, complete urine examination, urethral pus for gram staining and culture, endo-urethral swab with urethral loop for seeing Chlamydia antigen by fluorescent microscopy, cultures for ureaplasma and Wet mount specimen microscopy for trichomonas along with HIV (serum ELISA) test. Non-gonococcal urethritis was diagnosed on the presence of more than five polymorphonuclear leucocytes per high power field in at least five fields of Gram stained urethral smear, in the absence of Gram negative diplococci. RESULTS: The mean age was 29.2 + or - 5.8 years. Seventy (70%) cases were diagnosed as gonococcal urethritis and 30 (30%) cases as non-gonococcal urethritis (NGU). History of illicit sexual exposure was available in 25 (25%) patients. The interval period between initiation of symptoms and reporting of patient in gonococcal urethritis was 4 to 30 days (mean 12.8 days) and 4 days to 2 months (mean 20.7 days) in non-gonococcal urethritis. The patients with gonococcal urethritis presented with purulent discharge in 66 (84%) cases, and dysuria in 49 (70%) cases. In the NGU group, 25 (80%) cases had mucoid discharge and 18 (65%) had dysuria. in 70%, Neisseria gonorrhoeae was isolated, Chlamydia trachomatis in 16%, ureaplasma in 8%, and Trichomonas vaginalis in 4%. No organism could be detected in 2% cases. HIV test was negative in all cases. CONCLUSION: Gonococcal urethritis was the commonest urethritis seen followed by Chlamydia infection in the studied group of adult males.

Comparison Of Efficacy Of Permethrin 5% Cream With Crotamiton 10% Cream In Patients With Scabies.

BACKGROUND: Scabies is a common dermatological presentation in Pakistan. Permethrin and Crotamiton both are used widely for treating scabies. As there is no local study available regarding comparison of efficacy of Permethrin and Crotamiton in patients of scabies, current study was undertaken. The objective of the study was to compare the efficacy of 5% Permethrin with 10% Crotamiton in patients of scabies. METHODS: A Randomized control trial was conducted at Dermatology Department, Military Hospital, Rawalpindi. One hundred and sixty patients with scabies (diagnosis made by scraping the burrows to extract mite, larva or eggs and to see under light microscope) were randomly assigned either to Permethrin or Crotamiton group. Patients were followed over for 4 weeks to determine the effectiveness of either treatment. RESULTS: A total of 160 patients were included in the study with a mean age of 45.49±17.047 years and ranging from 13-65 years. One hundred and one patients (63.1%) were male and remaining 59 patients (26.9%) were female. Treatment was effective in 81.3% patients being treated with 5% Permethrin and 53.8% in 10% Crotamiton group. Comparison of treatment showed superiority of 5% Permethrin over 10% Crotamiton (p=0.001). There was no effect of age and gender on this outcome difference. CONCLUSIONS: Our study concludes that 5% Permethrin cream is significantly superior to 10% Crotamiton cream in treating patients of scabies (81.3% vs. 53.8%, p=0.001).

Drug induced linear IgA disease with unusual features: Koebner phenomenon, local insulin sensitivity and annular blister of the nipples.

Linear IgA disease is an autoimmune subepidermal bullous disease in which linear IgA deposits are found at the basement membrane zone. It is classically idiopathic but may be drug induced. We report on a patient with drug induced linear IgA disease who exhibited certain unusual and interesting clinical features including isomorphic Koebner response, annular blister of the nipples and local insulin sensitivity. To the best of our knowledge, these clinical features have not yet been reported in linear IgA disease.

Localized lesions in secondary syphilis.

The clinical manifestations of secondary syphilis are variable and can mimic many skin diseases, mostly being generalized and symmetrical in distribution. Localized lesions of secondary syphilis are rarely seen in dermatology clinics. We report an unusual presentation wherein a patient had localized lesions over face and soles only. There is a need for increased awareness on the part of physicians to recognize new patterns of syphilitic infection, together with a willingness to consider the diagnosis of syphilis in patients with unusual clinical features.

Comparison of 30% salicylic acid with Jessner's solution for superficial chemical peeling in epidermal melasma.

OBJECTIVE: To compare the efficacy and safety of Jessner's solution with 30% salicylic acid as superficial chemical peeling agents in treating epidermal melasma in Asian skin. STUDY DESIGN: Double blind, randomized, interventional comparative study. PLACE AND DURATION OF STUDY: Department of Dermatology, Combined Military Hospital, Malir Cantt, Karachi, from January to December 2004. PATIENTS AND METHODS: Sixty consenting patients with epidermal melasma were randomly divided into two groups. Group A was treated with Jessner's solution and Group B with 30% salicylic acid. Baseline Melasma Area Severity Index (MASI) score was noted and peeling started at 2-weekly intervals. Sunscreen in morning and moisturizer at night were prescribed in all patients. MASI score and adverse effects were recorded biweekly. Treatment was stopped at 12 weeks and patients were followed-up at 4 weekly intervals for further 12 weeks. Final MASI score and adverse effects were noted at the end of follow-up period. Mean MASI scores were compared using paired sample t-test and one-way ANOVA. RESULTS: Difference in baseline, treatment end and follow-up end MASI scores was not statistically significant between the two groups (p 0.54, 0.26, and 0.55 respectively). On the other hand, within group analysis of difference between pre and posttreatment MASI score was highly significant in both groups (p<0.0001). Adverse effects were mild and comparable in both groups. CONCLUSION: Jessner's solution and 30% salicylic acid are equally effective and safe peeling agents for use in epidermal melasma in Asian skin.

Papulonecrotic tuberculids associated with uveitis.

Papulonecrotic tuberculids represent an immunological expression of an internal focus of tuberculosis in an individual with a moderate or high degree of immunity. It responds to anti-tuberculosis treatment and is characterized by an eruption of necrotizing papules occurring in symmetrical crops, particularly affecting the elbows, knees, buttocks and face. A case of papulonecrotic tuberculids associated with immune mediated unilateral uveitis is reported in which all investigations were negative for tuberculosis except a strongly positive tuberculin test. There was an excellent response to anti-tuberculosis treatment. The association of immune mediated uveitis with papulonecrotic tuberculids has not been described before.

Onset of adult varicella in relation to rural or urban origin and its complications.

OBJECTIVES: To determine area of origin of adult varicella patients, whether rural or urban, to compare the mean interval between leaving the area of origin and onset of varicella in adults of rural origin in comparison with those of urban origin and to observe its complications. STUDY DESIGN: A cross-sectional study. PLACE AND DURATION OF STUDY: Combined Military Hospital, Abbottabad, from January to December 2006. PATIENTS AND METHODS: All patients over the age of 18 years, presenting with acute illness clinically, suggestive of varicella were included in the study. A specially designed proforma was filled for each patient separately, which included demographic features as well as area of origin, whether rural or urban, and the age at which they left the area of origin. These patients were examined, treated and assessed clinically on regular basis for the progress of the disease as well as for its possible local or systemic complications. Data analysis was done by using statistical programme SPSS-10. RESULTS: Out of 9155 adult patients, 156 (1.70%) had varicella, including 128 (82.1%) males and 28 (17.9%) females. Origin was rural in 125 (80.1%) and urban in 31 (19.9%) patients. Mean interval between leaving area of origin and developing varicella in those of rural origin was 01.79+/-01.78 years and that in patients of urban origin was 03.37+/-05.72 years (p+/-0.009). None of the patients developed any complication of the disease. CONCLUSION: Varicella in adults is generally a benign illness. It is more common among adult males of rural origin and the interval between leaving the area of origin and onset of varicella in these patients is significantly less as compared to that in adults of urban origin.

Clinical study of papular urticaria.

OBJECTIVE: To determine the clinical features and demographic profile of the patients having papular urticaria. STUDY DESIGN: A case-series. PLACE AND DURATION OF STUDY: Dermatology Department of Combined Military Hospital, Abbottabad from January to December 2006. PATIENTS AND METHODS: Individuals of all age groups and either gender either suspected of or having definite history of insect bite were included in the study. A specially-designed proforma was filled for each patient separately. The proforma included demographic features, information regarding clothing and sleeping habits, personal or family history of atopy and clinical patterns of the lesions. Computer programme SPSS 10 was used to manage and analyze the data. RESULTS: Out of 280 patients, 201 (71.8%) were children upto 12 years of age, 178 (63.6%) were males, 91 (32.5%) had atopy, 194 (69.3%) were non-locals, 212 (75.7%) came from urban/peri-urban areas and 173 (61.8%) presented during May-August. Lesions were present over exposed parts of the body in 36 (12.9%), arranged in groups in 152 (54.3%) and were papular urticaria in 185 (66.1%) patients. CONCLUSION: Children, adult males, non-locals and those belonging to urban/peri-urban areas are more vulnerable to papular urticaria in a particular region. Papular and urticarial lesions arranged in groups over both exposed as well as covered body parts of a single patient is the most common clinical pattern.