Understanding how geographic, demographic and treatment history impact health outcomes of patients with multi-drug-resistant tuberculosis in Pakistan, 2014-2017.

Tuberculosis (TB) is one of the top 10 leading causes of morbidity and mortality worldwide [1]. In 2017, approximately 10 million people were infected with TB and 1.3 million patients faced mortality [1]. Patients with active TB can infect up to 10-15 people over a year. There is a greater risk of transmission in overcrowded areas with limited air ventilation including large family units, prisons and slums [1, 2]. Without proper diagnosis and treatment, roughly 45% of non-HIV positive TB patients face mortality [1]. With the help of global organizations and national TB treatment and control programmes, the global incidence of TB is declining by approximately 2% each year [1]. The World Health Organization (WHO) TB-strategy aims to end the TB epidemic and encourages partners to fund national TB programmes to improve diagnosis and treatment of TB. The goal is to ultimately decrease death rates by 90% and decrease incidence rates by 80% [1]. To achieve these goals, the decline in TB incidence needs to reach approximately 4-5% per year [1]. The WHO 2018 TB report identified multidrug resistant TB (MDR-TB) as the leading factor hindering that goal [1]. The incidence and spread of MDR-TB has drastically increased, where approximately 558 000 new cases of MDR-TB were diagnosed in 2017 causing more than 230 000 deaths globally [1]. MDR-TB is identified by resistance to the two most powerful anti-TB treatment drugs including isoniazid and rifampicin [3]. Patients with MDR-TB are required to start second-line anti-TB drugs (SLDs), which are limited, expensive, less effective and more toxic [1,2]. Therapy duration is one of the major limitations of second-line treatments, which may require up to two years of consistent use. Since TB affects mostly developing countries, long treatment durations and associated costs become a major challenge. In 2015, 15% of new TB cases were reported as MDR-TB, which drastically increased to 24% by 2017 [1]. Even with significant improvements in molecular tests and diagnostic methods, MDR-TB is still on the rise where the success rate of treatments is between 50 and 60% [1]. Additional characteristics including socioeconomic and sociocultural factors need to be considered when targeting and treating patients with MDR-TB.

Bilateral transcutaneous tibial nerve stimulation for chronic constipation.

AIM: Chronic constipation is difficult to treat when symptoms are intractable. Colonic propulsion may be altered by distal neuromodulation but this is conventionally delivered percutaneously. Transcutaneous tibial nerve stimulation is noninvasive and cheap: this study aimed to assess its efficacy in chronic constipation. METHOD: Eighteen patients (median age 46 years, 12 female) with chronic constipation were recruited consecutively. Conservative and behavioural therapy had failed to improve symptoms in all 18. Thirty minutes of daily bilateral transcutaneous tibial nerve stimulation was administered by each patient at home for 6 weeks. The primary outcome measure was a change in the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. Change in Patient Assessment of Constipation Symptoms (PAC-SYM), weekly bowel frequency and visual analogue scale (VAS) score were also measured. RESULTS: Fifteen patients (12 female) completed the trial. The PAC-QoL score improved significantly with treatment [pretreatment, median 2.95, interquartile range (IQR) 1.18; posttreatment, median 2.50, IQR 0.70; P = 0.047]. There was no change in PAC-SYM score (pretreatment, median 2.36, IQR 1.59; posttreatment, median 2.08, IQR 0.92; P = 0.53). Weekly stool frequency improved as did VAS score, but these did not reach statistical significance (P = 0.229 and 0.161). The PAC-QoL and PAC-SYM scores both improved in four (26%) patients. Two patients reported complete cure. There were no adverse events reported. CONCLUSION: Bilateral transcutaneous tibial nerve stimulation appears to be effective in a quarter of patients with chronic constipation. Carefully selected patients with less severe disease may benefit more. This requires further study.

Oral supplementation of Ocimum basilicum has the potential to improves the locomotory, exploratory, anxiolytic behavior and learning in adult male albino mice.

The aim of this project was to determine the effect of 100 mg/ml solvent/kg body weight of Ocimum basilicum leaf extract on neuromuscular co-ordination, exploratory, locomotory and short-term memory formation in male albino mice. Five weeks old, male albino mice were used as the experimental animals in order to demonstrate the effect of O. basilicum's extract on learning and memory. Each male albino mouse was weighted and orally treated either with 100 mg/ml solvent/kg body weight of O. basilicum leaf extract or with commercially available saline solution (Otsuka, Pakistan) for 7 days. Behavioral observations were made by applying a series of neurological tests (Elevated plus maze, Light and dark box, Open field and Rota rod). Dose supplementation continued during neurological testing. It was observed that 100 mg/ml solvent/kg body weight of leaf extract improves neuromuscular co-ordination and male albino mouse performance in open field, light dark box and during novel object test when compared with control group. We concluded that 100 mg/ml solvent/kg body weight of leaf extract has the potential to improve neuromuscular co-ordination, exploratory behavior, object recognition ability and transfer latency in male albino mice and can be safely administrated orally.

Short Versus Regular Periods of Cast Immobilization for Distal Radial Fractures: A Systematic Review and Meta-Analysis.

The current research on the recommended durations for cast immobilization in adults with distal radial fractures (DRFs) lacks a clear consensus or definitive conclusion. The standard practice involves casting immobilization for five to six weeks. The debate revolves around the potential benefits of shorter periods (three to four weeks) without compromising patient outcomes. While previous research has delved into this subject through systematic reviews, our study stands out by conducting a meta-analysis, aiming for a more precise understanding of whether short or regular cast immobilization duration proves more effective for treating DRFs. A systematic search was conducted across PubMed, Embase, and the Cochrane Library databases to identify relevant studies. The focus was on comparing the outcomes of DRFs between short (three to four weeks) and regular (five to six weeks) periods of cast immobilization. The evaluated parameters include the shortened disabilities of the arm, shoulder, and hand questionnaire (quick (q) DASH); patient-rated wrist evaluation (PRWE); visual analog scale (VAS) score after cast removal; total complications; and the occurrence of complex regional pain syndrome (CRPS). Data synthesis employed the random-effects models, presenting the results as mean difference (MD) and weighted odds ratio (OR) with corresponding 95% confidence intervals (CI). We included three randomized controlled trials (RCTs) with 252 patients, of whom 125 (49.6%) were immobilized in a cast for three to four weeks. The average age of participants was 61.20 years, and the follow-up duration was one year. The QDASH scores were significantly lower at 12 weeks (MD -6.72; 95% CI -10.76 to -2.69; p = 0.001), six months (MD -4.46; 95% CI -7.42 to -1.50; p = 0.003), and one year (MD -4.89; 95% CI -7.45 to -2.33; p = 0.0002) in patients treated with short periods compared to those with regular periods. The PRWE scores at six months (MD -2.33; 95% CI -8.10 to 3.43; p=0.43) did not significantly differ between groups. Also, the PRWE scores were significantly lower at one year (MD -4.93; 95% CI -9.03 to -0.82; p = 0.02) in the shorter cast-immobilization-period group. There were no significant differences in VAS score after cast removal, total complications, or CRPS. The meta-analysis of RCTs on DRFs reveals that shorter periods of cast immobilization lead to better patient-reported functional outcomes (qDASH and PRWE). This suggests a potential benefit of reducing the immobilization duration for DRF patients, offering clinicians valuable insights for improved patient care and informed decision-making in clinical practice.

A comparison of two different techniques for the detection of blood parasite, Theileria annulata, in cattle from two districts in Khyber Pukhtoon Khwa Province (Pakistan).

The present study was carried out to determine the prevalence of Theileria annulata in large ruminants from two districts, Peshawar and Kohat, in Khyber Pukhtoon Khwa (Pakistan). Blood samples were collected from 95 cattle. Data on the characteristics of animals and herds were collected through questionnaires. No significant risk factors were found associated with the spread of tropical theileriosis in the study area. Two different parasite detection techniques, PCR amplification and screening of Giemsa stained slides, were compared and it was found that PCR amplification is a more sensitive tool (33.7% parasite detection), as compared to smear scanning (5.2% parasite detection) for the detection of Theileria annulata. 32 out of 95 animals, from both districts, produced the 721-bp fragment specific for Theileria annulata.

A study on the determination of risk factors associated with babesiosis and prevalence of Babesia sp., by PCR amplification, in small ruminants from Southern Punjab (Pakistan).

Babesiosis is a parasitic infection due to the multiplication of tick borne parasite, Babesia sp., in erythrocytes of host, which includes a wide variety of vertebrates including small ruminants causing decreased livestock output and hence economic losses. The objective of the present study was to establish a PCR based method for the detection of Babesia sp. in small ruminant population in Southern Punjab and to determine the risk factors involve in the spread of babesiosis. A total of 107 blood samples were collected from 40 sheep and 67 goats in seven districts of Southern Punjab from randomly selected herds. Data on the characteristics of the animals and the herd were collected through questionnaires. 36 blood samples (34% of total) produced the DNA fragment specific for 18S rRNA gene of Babesia sp., by PCR amplification, of which 20 were sheep and 16 were goats. Samples from all seven district contained Babesia positive samples and prevalence varied between 18 to 68%. It was observed that male animals (P = 0.009) and young animals under one year of age (P = 0.01) were more prone to the parasite. It was observed that herds consist of more than 15 animals (P = 0.007), composed of mixed species of small ruminants (P = 0.022), associated with dogs (P = 0.003) and dogs having ticks on their bodies (P = 0.011) were among the major risk factors for the spread of babesiosis in small ruminants.

Solifenacin for overactive bladder: secondary analysis of data from VENUS based on baseline continence status.

INTRODUCTION AND HYPOTHESIS: VENUS evaluated the efficacy of solifenacin on urgency in patients with overactive bladder (OAB). We hypothesized that solifenacin would be comparably efficacious in continent and incontinent patients. METHODS: VENUS was a 12-week, placebo-controlled trial in patients with OAB. Treatment efficacy was assessed using bladder diaries and patient-reported outcome measures. The primary endpoint was the change in daily urgency episodes. Exploratory subgroup analyses were conducted using baseline continence status. RESULTS: Solifenacin reduced urgency episodes versus placebo in continent (-3.4 vs. -2.3) and incontinent patients (-4.2 vs. -2.9) and incontinence episodes (-2.1 vs. -1.2) in that subgroup; 58% versus 42% of incontinent patients receiving solifenacin versus placebo were continent at study end. In both cohorts, solifenacin- versus placebo-treated patients showed greater improvements in perceptions of urgency severity, symptom bother, and health-related quality of life. CONCLUSION: This post hoc analysis demonstrates the efficacy of solifenacin regardless of baseline continence status.

Metastatic insulinoma presenting 14 years after benign tumour resection: a rare case and management dilemma.

SUMMARY: We present a 60-year-old woman who underwent successful surgical resection (partial pancreatectomy) for a low grade non-functioning pancreatic neuroendocrine tumour (pNET), with no biochemical or radiological features of recurrence on follow-up visits for 5 years. Fourteen years after the initial surgery, she developed spontaneous severe hypoglycaemic episodes which required hospitalisation, with subsequent investigations confirming the diagnosis of a metastatic insulin-secreting pNET (insulinoma). Medical management of her severe spontaneous hypoglycaemic episodes remained challenging, despite optimum use of diazoxide and somatostatin analogue therapy. Based on a discussion at the regional neuroendocrine tumour multidisciplinary team meeting, she underwent an elective hepatic trans-arterial embolization which was unfortunately unsuccessful. She ended up requiring an emergency right hemihepatectomy and left retroperitoneal mass resection which finally stabilised her clinical condition. LEARNING POINTS: Ours is only the seventh case report of a previously benign pNET presenting as a functional insulin secreting metastatic tumour. However, it is the first case report, in which the metastatic functional pNET presented after such a long hiatus (14 years). There is currently no clear consensus regarding the length of follow-up of non-functional pNET which are deemed cured post-surgical resection, with most guidelines advocating a median follow up of 5 years (1). The delayed presentation in our case suggests additional considerations should be made regarding optimal post-operative surveillance duration based on the age of the patient, location of the tumour, lymph node spread and Ki-67 index. Hepatic artery embolization and/or partial hepatectomy remains a treatment option for pNET patients with significant hepatic metastasis.

Molecular detection of Babesia microti in dogs and cat blood samples collected from Punjab (Pakistan).

Babesia microti (B. microti) is an intra erythrocytic protozoan that mainly infects red blood cells and causes babesiosis. Its frequent hosts are rodents, ticks and humans. Dog's blood samples (N = 150) were collected from three different districts in Punjab including Multan (N = 49), Islamabad/Rawalpindi (N = 49) and Lahore (N = 52) while 159 cat's blood samples were collected from Lahore (N = 159). Data on the epidemiological characters of all animals (including age, gender, breed, body temperature, deworming, vaccination, mucus membrane status, hydration status, presence of hematuria and tick infestation) was collected through questionnaire. Polymerase chain reaction (PCR) amplified a 238 base pair amplicon specific for 18S rRNA gene of B. microti in two (1.3%) dog and 21 (13.2%) cat blood samples. Amplified PCR products were confirmed by DNA sequencing and the four partial 18S rRNA gene sequences were submitted to the EMBL/GenBank. Among epidemiological factors, high body temperature (P < 0.05) and pale mucous membrane (P < 0.05) were the parameters associated with the presence of B. microti in infected dogs. Females were found to be more infected (P = 0.05) than males and incidence of B. microti infection was higher in cat samples collected during winter months (P = 0.0001) than in summer. In conclusion, we are reporting the prevalence of B. microti in blood samples of cats and dogs from Pakistan for the first time and recommending that this Protozoan parasite should be considered for screening in cats and dogs with compatible clinical signs.

Remotely-sensed land use patterns and the presence of Anopheles larvae (Diptera: Culicidae) in Sukabumi, West Java, Indonesia.

Land use patterns and the occurrence of Anopheles species larvae were studied in Sukabumi District, West Java, Indonesia, from October 2004 to September 2005. Two land use maps derived using remote sensing were used. One map derived from Quickbird satellite images of 150 km2 of the Simpenan and Ciemas subdistricts (106 degrees 27' 53"-106 degrees 38' 38" E and 6 degrees 59' 59"-7 degrees 8' 46" S) in Sukabumi and one using ASTER images covering 4,000 km2 of Sukabumi District from 106 degrees 22' 15"-107 degrees 4' 1" E and 6 degrees 42' 50" - 7 degrees 26' 13" S. There was a total of 11 Anopheles spp. collected from 209 sampling locations in the area covered by the Quickbird image and a total of 15 Anopheles spp. collected from 1,600 sampling locations in the area covered by the ASTER map. For the area covered by the land use maps, ten species were found to have statistically positive relationships between land use class and species presence: Anopheles aconitus, An. annularis, An. barbirostris. An. flavirostris, An. insulaeflorum, An. kochi, An. maculatus, An. subpictus, An. sundaicus, and An. vagus. Quickbird and ASTER satellite images both produced land maps that were adequate for predicting species presence in an area. The land use classes associated with malaria vector breeding were rice paddy (An. aconitus, An. subpictus), plantation located near or adjacent to human settlements (An. maculatus), bush/shrub (An. aconitus, An. maculatus, An. sundaicus), bare land, and water body land use on the coast located < or = 250 m of the beach (An. sundaicus). Understanding the associations of habitat and species in one area, predictions of species presence or absence can be made prior to a ground survey allowing for accurate vector survey and control planning.

Triple primary cancers of the larynx, lung and thyroid presenting in one patient.

Patients with multiple malignant primary tumours are often described, based on their chronology of presentation, as simultaneous, synchronous or metachronous tumours. Lung malignancies presenting in association with head and neck tumours are well documented while there have been small series of thyroid synchronous cancers presenting with laryngeal lesions in literature. No cases, to our knowledge, have been reported in literature of a single patient with all three laryngeal, lung and thyroid malignancies. We report one such case of a 71-year-old Chinese man who had undergone a total laryngectomy for a recurrent cancer of the larynx only to be found to have tumours of the lung and thyroid in the post-operative period and he eventually died of post-operative complications. We also discuss screening for lung and thyroid malignancies in patients with head and neck squamous cell carcinoma (SCC).

Empty Nose Syndrome post radical turbinate surgery.

Empty Nose Syndrome (ENS) is a rare and controversial sequelae from previous radical turbinate surgery. We report on a 50-year-old Chinese gentleman with long-standing nasal problems who has had radical turbinate surgery many years prior to presenting at the ENT clinic with mucoid nasal discharge and chronically blocked nose. His nasal cavities were ironically very patent and there were only minor remnants of his turbinates bilaterally. We treated him medically for several years with nasal steroids, antihistamines and leukotriene receptor antagonists and his nasal symptoms have reduced significantly.

Subcutaneous implant breast reconstruction: Time to reconsider?

Improvements in breast surgery techniques such as skin and nipple preserving mastectomy and innovative prosthetics (implants, acellular dermal matrices and meshes) is renewing interest in subcutaneous (pre-pectoral) implant reconstruction. The aim of this paper is to review the current literature in an attempt to provide a rationale that may support a return to subcutaneous implant placement, so minimising the pain and functional problems resulting from submuscular breast reconstruction.

Molecular detection of Anaplasma in apparently healthy Cholistan breed of cattle from the Bahawalpur district, Pakistan.

The present study was designed to report the prevalence of Anaplasma sp. in blood samples of Cholistan breed of cattle from Bahawalpur District and to determine the risk factors associated with the prevalence of this parasite. A total of 148 blood samples were randomly collected from apparently healthy cattle. On the sampling sites, data on the characteristics of the animals (species, gender, age) were collected through questionnaires. 47 blood samples (31.8% of total) produced the 577 base pairs DNA fragment specific for 16S rRNA gene of Anaplasma sp. by PCR amplification. Out of 47 Anaplasma sp. positive PCR products, 9 were found to be Anaplasma marginale by restriction with BssNa1 and 9 were confirmed to be Anaplasma phagocytophilum (A. phagocytophilum) as they amplified 550 bp fragment from the amplified MSP 2 gene of this species. Risk factor analysis indicated that the presence of parasite was not limited to a particular sex or age group of the infected animals. Comparison of hematological profile revealed that Anaplasma sp. positive cattle had significantly reduced levels of mean corpuscular volume (P=0.02) and eosinophils (P=0.02) than in parasite negative animals. While studied serum biochemical profile remain unaffected when compared between the two groups.

Chronic cholestasis in patients on parenteral nutrition: the influence of restoring bowel continuity after mesenteric infarction.

BACKGROUND/OBJECTIVES: Patients with a short bowel and receiving parenteral nutrition (PN) have an increased risk of chronic cholestasis (CC). Restoration of bowel continuity after a mesenteric infarction results in PN requirements being reduced or stopped. This study aimed to determine the prevalence of CC and whether restoring bowel continuity reduced the risk of CC. SUBJECTS/METHODS: A retrospective review of patients with a short bowel owing to mesenteric infarction from 2000 to 2012. CC was defined as two of bilirubin, alkaline phosphatase and gamma-glutamyl transferase being 1.5 times the upper limit of normal for >6 months. RESULTS: We identified 104 (55 females, median age 54 years) patients. Seventy-three (70%) patients had restoration of bowel continuity; of these, 25 (34%) had abnormal liver biochemistry (liver function test (LFT)), with 15 (21%) having CC. Following restoration of bowel continuity, 8 (53%) of 15 patients with CC and 10 (100%) of 10 patients with abnormal LFT but not CC had a return of liver function within normal range within a year. Univariate analysis showed restoring bowel continuity (P=0.002) and cessation of PN (P=0.006) were associated with a reduction in prevalence of CC. Multivariate analysis showed that cessation of PN was a significant factor in reducing CC (P=0.02). CONCLUSIONS: The prevalence of CC is 29% for patients with a short bowel receiving PN following a mesenteric infarction. CC resolves in 53% after continuity is restored, and this is most likely due to stopping or reducing the PN.

A report on the molecular detection and seasonal prevalence of Trypanosoma brucei in Dromedary Camels from Dera Ghazi Khan District in Southern Punjab (Pakistan).

The present study was designed for molecular detection of Trypanosoma brucei through PCR, by using kinetoplast DNA (kDNA) maxicircle primers, on seasonal basis and to demonstrate the effect of this parasite on complete blood count and selected parameters of serum biochemistry in camels from Southern Punjab (Pakistan). A total of 291 camel blood samples (61 male, 230 females) were collected from Dera Ghazi Khan District in Pakistan during March 2012 till February 2013 for Trypanosoma brucei detection by blood smear screening, micro hemato centrifugation and Polymerase chain reaction techniques. Twenty eight out of 291 blood samples (9.62%) produced a 164 bp DNA fragment specific for T. brucei. Only 6 blood samples (2.06%) were found parasite positive by microscopic examination and 13 (4.46%) were positive for microhematocrit centrifugation technique. Seasonal PCR based prevalence of trypanosomiasis was 6.9%, 13.7%, 9.7% and 8.1% during spring, summer, autumn and winter seasons respectively. T. brucei prevalence was not restricted to a particular age group or and gender of the studied animals (P > 0.05). A significant increase in WBC (P = 0.001), neutrophils (P = 0.004), ALT (P = 0.028) and decreased RBC (P < 0.000), hemoglobin (P < 0.000) and packed cell volume (P < 0.000) were detected in parasite positive as compared to the parasite negative blood samples. In conclusion, PCR is a more reliable and sensitive technique than conventional microscopic blood screening and microhematocrit centrifugation for the detection of T. brucei in camel blood. We recommend the use of PCR for the effective prophylactic detection of T. brucei in livestock in order to reduce economic losses.

PCR based detection of Theileria lestoquardi in apparently healthy sheep and goats from two districts in Khyber Pukhtoon Khwa (Pakistan).

The present study was carried out to determine the prevalence of Theileria lestoquardi from two districts of Khyber Pukhtoon Khwa (Kohat and Peshawar) in Pakistan and also to report the risk factors associated with the spread of ovine theileriosis. A total of 165 blood samples were collected from sheep (N = 44) and goats (N = 121) from randomly selected herds. Data on the characteristics of animals and the herds were collected through questionnaires. Five (3%) out of total 165 samples produced 730 base pairs DNA fragment, through PCR amplification of 18S SSU rRNA gene, specific for T. lestoquardi. All positive samples were from district Kohat while samples from Peshawar were found negative for this parasite. Statistical analysis indicated a significant association (P = 0.005) between sampling site and prevalence of T. lestoquardi. It was observed that presence of tick on the ruminant (P = 0.0007) and the dogs associated with the herd (P = 0.001) were highly significant risk factor for the spread of ovine theileriosis. It was also observed that mixed herds (containing both sheep and goats) were more prone to the parasite. We have concluded that PCR is a sensitive and reliable diagnostic tool for detection of T. lestoquardi in blood samples of small ruminants and can be used for the prophylactic screening and treatment of this blood parasite in order to increase the live stock production in Pakistan.