Effect of haemodialysis practice guideline on dialysis indicators and haemodynamic complications among patients undergoing haemodialysis.

To assess the effect of haemodialysis practice guidelines on dialysis indicators and haemodynamic complications, the comparative study was conducted at the dialysis unit of Sheikh Zayed Hospital, Lahore, Pakistan, and comprised patients undergoing haemodialysis who were divided into intervention group A in which updated haemodialysis practice guidelines were used, and control group B in which routine base dialysis was given. Data was collected using a self-structured tool. Data was analysed using McNemar test and Mann-Whitney U-test with p<0.05. Compared to baseline, there was a significant improvement in post-intervention ratio of effective removal of clearance (K) resulting from the treatment characterised by time (t) in the patient with a specific volume of distribution (V), or Kt/V, median & IQR 0.83(0.355) vs 1.21(0.11) and percentage of urea reduction ratio with median & IQR 49(12) vs. 66.5(18.65) (p<0.05). Intradialytic hypotension was found in 17(56.6%) subjects in group B and in 4(13.4%) in group A (p=0.002). Intradialytic hypertension was found in 8(25.6%) patients in group B and 1(3.4%) in group A (p=0.039). It is recommended that dialysis be performed in accordance with the most recent clinical guidelines in order to improve practices and to increase haemodialysis effectiveness.

A vision for nursing in Pakistan: is the change we need possible?

Adnan Yaqoob, Assistant Professor, Lahore School of Nursing, The University of Lahore, sets out his vision for the future of nursing in Pakistan.

Prevalence of molecular markers of sulfadoxine-pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan.

BACKGROUND: In Pakistan, artesunate (AS) in combination with sulfadoxine-pyrimethamine (SP) is the recommended treatment for uncomplicated Plasmodium falciparum malaria. Monitoring molecular markers of anti-malarial drug resistance is crucial for early detection and containment of parasite resistance to treatment. Currently, no data are available on molecular markers of artemisinin resistance (K13 mutations) in P. falciparum isolates from Pakistan. In this study, the prevalence of mutations associated with SP and artemisinin resistance was estimated in different regions of Pakistan. METHODS: A total of 845 blood samples that were positive for malaria parasites by microscopy or rapid diagnostic test were collected from January 2016 to February 2017 from 16 different sites in Pakistan. Of these samples, 300 were positive for P. falciparum by PCR. Polymorphisms in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by pyrosequencing while polymorphisms in the propeller domain of the pfk13 gene were identified by Sanger sequencing. RESULTS: The prevalence of the PfDHFR 108N and 59R mutations was 100% and 98.8%, respectively, while the prevalence of PfDHFR 50R and 51I mutations was 8.6%. No mutation was observed at PfDHFR position 164. In PfDHPS, the prevalence of mutations at positions 436, 437, and 613 was 9.9%, 45.2%, and 0.4%, respectively. No mutations were found at PfDHPS positions 540 and 581. The prevalence of double PfDHFR mutants (59R + 108N) ranged from 93.8% to 100%, while the prevalence of parasites having the PfDHFR 59R + 108N mutations in addition to the PfDHPS 437G mutation ranged from 9.5% to 83.3% across different regions of Pakistan. Nine non-synonymous and four synonymous mutations were observed in the PfK13 propeller domain, none of which correspond to mutations validated to contribute to artemisinin resistance. CONCLUSION: The absence of the highly resistant PfDHFR/PfDHPS quintuple mutant parasites and the lack of PfK13 mutations associated with artemisinin resistance is consistent with AS + SP being effective in Pakistan.

Prevalence and distribution of human Plasmodium infection in Pakistan.

BACKGROUND: Both Plasmodium vivax and Plasmodium falciparum are prevalent in Pakistan, yet up-to-date data on the epidemiology of malaria in Pakistan are not available. This study was undertaken to determine the current prevalence and distribution of Plasmodium species across the country. METHODS: A malariometric population survey was conducted in 2011 using blood samples collected from 801 febrile patients of all ages in four provinces and the capital city of Islamabad. Microscopically confirmed Plasmodium-positive blood samples were reconfirmed by polymerase chain reaction (PCR). Confirmed parasite-positive samples were subjected to species-specific PCR capable of detecting four species of human malaria. RESULTS: Of the 707 PCR-positive samples, 128 (18%) were P. falciparum, 536 (76%) were P. vivax, and 43 (6%) were mixed P. falciparum and P. vivax. Ninety-four microscopy-positive samples were PCR-negative, and Plasmodium malariae and Plasmodium ovale were not detected. Prevalence of P. vivax ranged from 2.4% in Punjab Province to 10.8% in Sindh Province and prevalence of P. falciparum ranged from 0.1% in Islamabad to 3.8% in Balochistan. CONCLUSIONS: Plasmodium infections in Pakistan are largely attributed to P. vivax but P. falciparum and mixed species infections are also prevalent. In addition, regional variation in the prevalence and species composition of malaria is high.

Home-based cardiac rehabilitation: development, implementation and outcome evaluation in patients with coronary artery diseases in Lahore, Pakistan - a mixed-methods study protocol.

INTRODUCTION: Cardiac rehabilitation (CR) is an important strategy to bring cardiac patients back to a normal life after a cardiac event. The benefits of CR as part of secondary prevention are widely known among people who have undergone myocardial infarction or revascularisation. As evidenced by several systematic reviews and meta-analyses, home-based CR (HBCR) has similar or greater effects on health-related quality of life, health outcomes, physical activity, anxiety and unplanned visits to the emergency department as compared with centre-based CR. The purpose of this study is to develop a contextual HBCR intervention and evaluate its effects on quality of life, health behaviours, bio-physiological parameters and emergency hospital visits of patients with coronary artery diseases in Lahore, Pakistan. METHODS AND ANALYSIS: This study will employ a mixed-method exploratory sequential research design. The researchers will invite 15-20 cardiac patients and 12-15 healthcare providers for semi-structured interviews in the qualitative phase of the study. Once the intervention is developed and validated through the qualitative phase, the outcomes will be evaluated through a single-blinded randomised control trial in the quantitative phase. A total of 118 patients with acute coronary syndrome will be recruited through a screening checklist and randomly allocated into the control and intervention groups (59 patients in each group). The inductive coding approach will be used for the thematic analysis of qualitative data, whereas the quantitative data will be analysed through descriptive and inferential statistics using SPSS to see the difference within the groups, between groups and between three intervals. ETHICS AND DISSEMINATION: The Ethical Review Committee of Aga Khan University and Mayo Hospital Lahore under the registration number 2023-8282-24191 and No/75749MH have approved this study protocol, respectively. The results of this study will be disseminated to participating patients (in the Urdu language), healthcare professionals and the public by publishing the manuscript in an open-access peer-reviewed journal and presenting it at different conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ACTRN12623000049673p).

Assessment of Microscopic Detection of Malaria with Nested Polymerase Chain Reaction in War-Torn Federally Administered Tribal Areas of Pakistan.

INTRODUCTION: Diagnostic accuracy of malaria is critical for early treatment, control, and elimination of malaria, especially in war-affected malaria-endemic areas. Microscopic detection of Plasmodium species has been the gold standard in remote malaria-endemic regions. However, the diagnostic accuracy is still questioned, especially in discriminating mixed and submicroscopic parasitic levels. This study was designed to evaluate the diagnostic performance of microscopic examination against nested PCR analysis in war-torn malaria-endemic Federally Administered Tribal Areas (FATA) of Pakistan. METHODS: Venous blood samples were collected from symptomatic patients for microscopic examination and nested PCR analysis from January 2016-December 2016 from five Agencies (Bajaur, Mohmand, Khyber, Orakzai and Kurram Agency) and four Frontier Regions (Peshawar, Kohat, Bannu, and Dera Ismail Khan Frontier Region) of FATA. Malaria-positive isolates were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes) for speciation. RESULTS: Among enrolled participants, 762 were found positive for malaria parasite on microscopic examination of the blood film. Plasmodium vivax was found in 623, Plasmodium falciparum in 132 and 7 were diagnosed with mixed infection (P. vivax and P. falciparum coinfection). Nested PCR detected Plasmodium infection in 679 samples (523 P. vivax, 121 P. falciparum, and 35 mixed infections). Compared with microscopy, the sensitivity of nested PCR was 98.94%, and specificity was 98.27%, while the sensitivity and specificity of slide microscopy 89.34% and 87.99% respectively. CONCLUSION: The conventional microscopy method has low sensitivity to detect the mixed infection as compared to nested PCR. High sensitivity and specificity observed in nested PCR make this molecular tool a useful technique for monitoring, controlling, and eliminating malaria-endemic regions.

Surveillance of molecular markers of antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Federally Administered Tribal Area (FATA), Pakistan.

This molecular epidemiological study was designed to determine the antimalarial drug resistance pattern, and the genetic diversity of malaria isolates collected from a war-altered Federally Administered Tribal Area (FATA), in Pakistan. Clinical isolates were collected from Bajaur, Mohmand, Khyber, Orakzai and Kurram agencies of FATA region between May 2017 and May 2018, and they underwent DNA extraction and amplification. The investigation of gene polymorphisms in drug resistance genes (dhfr, dhps, crt, and mdr1) of Plasmodium falciparum and Plasmodium vivax was carried out by pyrosequencing and Sanger sequencing, respectively. Out of 679 PCR-confirmed malaria samples, 523 (77%) were P. vivax, 121 (18%) P. falciparum, and 35 (5%) had mixed-species infections. All P. falciparum isolates had pfdhfr double mutants (C59R+S108N), while pfdhfr/pfdhps triple mutants (C59R+S108N+A437G) were detected in 11.5% of the samples. About 97.4% of P. falciparum isolates contained pfcrt K76T mutation, while pfmdr1 N86Y and Y184F mutations were present in 18.2% and 10.2% of the samples. P. vivax pvdhfr S58R mutation was present in 24.9% of isolates and the S117N mutation in 36.2%, while no mutation in the pvdhps gene was found. Pvmdr1 F1076L mutation was found in nearly all samples, as it was observed in 98.9% of isolates. No significant anti-folate and chloroquine resistance was observed in P. vivax; however, mutations associated with antifolate-resistance were found, and the chloroquine-resistant gene has been observed in 100% of P. falciparum isolates. Chloroquine and sulphadoxine-pyrimethamine resistance were found to be high in P. falciparum and low in P. vivax. Chloroquine could still be used for P. vivax infection but need to be tested in vivo, whereas a replacement of the artemisinin combination therapy for P. falciparum appears to be justified.