Macrolides for better resolution of community-acquired pneumonia: A global meta-analysis of clinical outcomes with focus on microbial aetiology.

OBJECTIVES: This meta-analysis examined the effect of macrolides on resolution of community-acquired pneumonia (CAP) and interpretation of clinical benefit according to microbiology; emphasis is given to data under-reported countries (URCs). METHODS: This meta-analysis included 47 publications published between 1994 and 2022. Publications were analysed for 30-d mortality (58 759 patients) and resolution of CAP (6465 patients). A separate meta-analysis was done for the prevalence of respiratory pathogens in URCs. RESULTS: Mortality after 30 d was reduced by the addition of macrolides (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.82). The OR for CAP resolution when macrolides were added to the treatment regimen was 1.23 (95% CI 1.00-1.52). In the CAP resolution analysis, the most prevalent pathogen was Streptococcus pneumoniae (12.68%; 95% CI 9.36-16.95%). Analysis of the pathogen epidemiology from the URCs included 12 publications. The most prevalent pathogens were S. pneumoniae (24.91%) and Klebsiella pneumoniae (12.90%). CONCLUSION: The addition of macrolides to the treatment regimen led to 35% relative decrease of 30-d mortality and to 23% relative increase in resolution of CAP.

GRADE-ADOLOPMENT of clinical practice guidelines and creation of clinical pathways for the primary care management of chronic respiratory conditions in Pakistan.

INTRODUCTION: In Pakistan, chronic respiratory conditions contribute a large burden of morbidity and mortality. A major reason for this is the lack of availability of local evidence-based clinical practice guidelines (EBCPGs) in Pakistan, particularly at the primary care level. Thus, we developed EBCPGs and created clinical diagnosis and referral pathways for the primary care management of chronic respiratory conditions in Pakistan. METHODS: The source guidelines were selected by two local expert pulmonologists after a thorough literature review on PubMed and Google Scholar from 2010 to December 2021. The source guidelines covered idiopathic pulmonary fibrosis, asthma, chronic obstructive pulmonary disorders, and bronchiectasis. The GRADE-ADOLOPMENT process consists of three key elements: adoption (using recommendations as is or with minor changes), adaptation (effective context-specific changes to recommendations) or additions (including new recommendations to fill a gap in the EBCPG). We employed the GRADE-ADOLOPMENT process to adopt, adapt, adopt with minor changes, or exclude recommendations from a source guideline. Additional recommendations were added to the clinical pathways based on a best-evidence review process. RESULTS: 46 recommendations were excluded mainly due to the unavailability of recommended management in Pakistan and scope beyond the practice of general physicians. Clinical diagnosis and referral pathways were designed for the four chronic respiratory conditions, explicitly delineating the role of primary care practitioners in the diagnosis, basic management, and timely referral of patients. Across the four conditions, 18 recommendations were added (seven for IPF, three for bronchiectasis, four for COPD, and four for asthma). CONCLUSION: The widespread use of the newly created EBCPGs and clinical pathways in the primary healthcare system of Pakistan can help alleviate the morbidity and mortality related to chronic respiratory conditions disease in the country.

Post-COVID-19 sequelae of the respiratory system. A single-centre experience reporting the compromise of the airway, alveolar and vascular components.

The long-term sequelae of COVID-19 have now become more common and appreciable. The SARS-CoV-2 virus can cause a variety of infectious and non-infectious pulmonary complications. The purpose of this study is to raise awareness about post-COVID-19 pulmonary sequelae, both infectious and non-infectious, in this geographical area. A retrospective study was conducted from July 1st 2020 to December 20th 2020. A total of 1200 patients were evaluated, with 83 suffering from post-COVID-19 pulmonary complications. The patients' mean age was 62 years (IQR 55-69), with 63 (75.9%) being male. The most common co-morbid illnesses were hypertension (49, 59%) and diabetes (45, 54.2%). The majority of them (37, 44.6%) had severe COVID-19, followed by critical COVID-19 (33, 39.8%). There was no statistically significant difference in recurrence of respiratory symptoms or duration of current illness between non-severe, severe, and critical COVID-19 patients. Non-infectious complications were observed in the majority of patients (n=76, 91.5%), including organizing pneumonia/ground glass opacities in 71 (88%) patients, fibrosis in 44 (55%), pulmonary embolism in 10 (12.5%), pneumomediastinum in 6 (7.4%) and pneumothorax in 7 (8.6%). Infective complications (25, 30.1%) included aspergillus infection in 10 (12.0%) and bacterial infection in 5 (8.47%), with more gram-negative infections and one patient developing Mycobacterium tuberculosis. Post COVID-19 mortality was 11 (13.3%). The long-term pulmonary sequelae of COVID-19 are not rare. Cryptogenic organizing pneumonia, ground glass opacities, and fibrosis were common post-COVID-19 sequelae in our patients. This necessitates frequent close monitoring of these patients in order to initiate early appropriate management and prevent further morbidity and eventual mortality.

Residual symptoms and the quality of life in individuals recovered from COVID-19 infection: A survey from Pakistan.

BACKGROUND: There remains scarcity of literature regarding the patient's health status post-COVID-19 infection. This study analyzes the prevalence of residual symptoms and quality of life (QoL) after COVID-19. METHODS: An anonymous online survey was administrated in Pakistan from November 2020 to April 2021 in COVID-19 survivors. The questionnaire used the 12-Item Short Form Health Survey (SF-12) to assess mental and physical QoL. Multivariate linear regression was used to explore factors associated with mental and physical QoL scores. RESULTS: A total of 331 COVID-19 survivors participated in our survey. Around 42.0% of the cohort reported within 1-3 months of diagnosis of COVID-19. The common residual symptoms were body aches (39.9%), low mood (32.6%), and cough (30.2%). Better physical QoL was associated with being male (adjusted beta: 3.328) and having no residual symptoms (6.955). However, suffering from nausea/vomiting during initial COVID-19 infection (-4.026), being admitted to the ICU during COVID-19 infection (-9.164), and suffering from residual body aches (-5.209) and low mood (-2.959) was associated with poorer QoL. Better mental QoL was associated with being asymptomatic during initial COVID-19 infection (6.149) and post-COVID (6.685), while experiencing low mood post-COVID was associated with poorer mental QoL (-8.253 [-10.914, -5.592]). CONCLUSION: Despite presumed "recovery" from COVID-19, patients still face a wide range of residual symptoms months after initial infection, which contributes towards poorer QoL. Healthcare professionals must remain alert to the long-lasting effects of COVID-19 infection and aim to address them appropriately to improve patients' QoL.

The effect of ivermectin on non-severe and severe COVID-19 disease and gender-based difference of its effectiveness.

The COVID-19 pandemic has led to mortality and morbidity since December 2019. Many possible treatment options have been advised till date. The role of ivermectin in the treatment of COVID-19 disease remains controversial. The aim of our study was to evaluate the effect of ivermectin in hospitalized patients with non-severe and severe COVID-19 disease. We conducted a retrospective cohort study that compared outcomes in 2 groups of COVID-19 patients hospitalized at the largest tertiary care center of Pakistan. The study group was given ivermectin along with standard treatment of covid-19 disease; the comparison group was not. Data on mortality, inflammatory markers such as C-reactive protein (CRP) and ferritin, length of hospital stay and baseline characteristics were collected from Aga Khan University's database from October 2020 till February 2021. Statistical analysis was done to determine the effectiveness of ivermectin in non-severe and severe COVID-19. Comparison of effectiveness of Ivermectin in both the genders was also conducted. The cohort included 188 patients out of which 90 were treated with ivermectin. Mortality and length of hospitalization was not found to be significantly different in the study group compared with the control group (5.6% vs 5.1%; p=0.87 and 5 days vs 4 days; p=0.27). Analysis of secondary outcomes did not yield statistically significant results, apart from ferritin levels which were significantly less in patients treated with ivermectin (547.1 vs 756.7; p=0.03). The ferritin and CRP levels in affected males were higher than in females on admission and discharge. Our findings suggest ivermectin does not significantly affect all-cause mortality, length of hospitalization and CRP levels in hospitalized COVID-19 patients. Large scale randomized controlled trials (RCTs) are required to further evaluate the role of ivermectin in covid-19 disease.

Persistence of post-COVID lung parenchymal abnormalities during the three-month follow-up.

INTRODUCTION: COVID-19-associated pulmonary sequalae have been increasingly reported after recovery from acute infection. Therefore, we aim to explore the charactersitics of persistent lung parenchymal abnormalities in patients with COVID-19. MATERIAL AND METHODS: An observational study was conducted in patients with post-COVID lung parenchymal abnormalities from April till September 2020. Patients ≥18 years of age with COVID-19 who were diagnosed as post-COVID lung parenchymal abnormality based on respiratory symptoms and HRCT chest imaging after the recovery of acute infection. Data was recorded on a structured pro forma, and descriptive analysis was performed using Stata version 12.1. RESULTS: A total of 30 patients with post-COVID lung parenchymal abnormalities were identified. The mean age of patients was 59.1 (SD 12.6), and 27 (90.0%) were males. Four HRCT patterns of lung parenchymal abnormalities were seen; organizing pneumonia in 10 (33.3%), nonspecific interstitial pneumonitis in 17 (56.7%), usual interstitial pneumonitis in 12 (40.0%) and probable usual interstitial pneumonitis in 14 (46.7%). Diffuse involvement was found in 15 (50.0%) patients, while peripheral predominance in 15 (50.0%), and other significant findings were seen in 8 (26.7%) patients. All individuals were treated with corticosteroids. The case fatality rate was 16.7%. Amongst the survivors, 32.0% recovered completely, 36.0% improved, while 32.0% of the patients had static or progressive disease. CONCLUSION: This is the first study from Southeast Asia that identified post-COVID lung parenchymal abnormalities in patients who had no pre-existing lung disease highlighting the importance of timely recognition and treatment of this entity that might lead to fatal outcome.

Role of ivermectin in patients hospitalized with COVID-19: a systematic review of literature.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected almost every country in the world since De-cember 2019. Despite the efforts of the human race to combat the virus, we are still looking for an evidence-based permanent cure for the disease. Ivermectin has recently emerged as one of the therapies having a beneficial effect on COVID-19. Ivermectin, owing to its properties, continues to be a possible treatment against the COVID-19 disease. Already being a mainstream drug with minimal adverse effects, it garners valid consideration. It's use in hospitalized patients, randomized controlled trials, and observational studies has also supported its implementation. In this article, we have reviewed recent studies and explored the effectiveness of ivermectin in hospitalized COVID-19 patients.

Acceptance of COVID-19 Vaccine in Pakistan: A Nationwide Cross-Sectional Study.

Introduction The coronavirus disease 2019 (COVID-19) vaccine is available across various countries worldwide, with public-private partnerships ensuring all individuals are vaccinated through a phased approach. Irrespective of the geographical spread, several myths pertaining to the COVID-19 vaccine have stemmed, ultimately limiting the national administration of vaccines and rollouts. This study assessed the acceptance of the COVID-19 vaccine among the general public in Pakistan. Methods A pre-validated questionnaire was administered from January 2021 to February 2021 to assess the public attitude and acceptance of the COVID-19 vaccine. Logistic regression analyses were run to identify factors associated with the acceptance among the population. Results A total of 936 responses were elicited, where 15% perceived their risk of being infected at 20-30% with an overall 70% agreeing to be vaccinated if recommended. Multivariate analysis identified higher acceptance in the male gender, healthcare workers, and students. Of all, 66% respondents chose healthcare workers and public officials, whereas 15.6% chose scientific literature, and 12.9% chose social media as the most reliable source of COVID-19 information. Conclusion Given the relatively greater trust in healthcare providers for information regarding COVID-19, healthcare workers ought to be on the frontline for vaccine campaigns and public outreach efforts, with governmental efforts in addition to the promotion of scientific materials for population-level understanding.

National Registry of Interstitial Lung Disease from Pakistan.

Introduction Interstitial lung disease (ILD) is a heterogeneous group of over 200 parenchymal lung diseases with a myriad of etiologies. Interstitial lung disease registries from around the world show varying prevalence and incidence of these diseases. The aim of this study was to determine the epidemiology and characteristics of ILD in Pakistan. Methods This web-based registry, which is the first multicenter registry of ILD from Pakistan, recruited patients from 10 centers of five major cities between January 2016 and March 2019. Results A total of 744 patients were enrolled in the registry. The five most frequent ILDs were idiopathic pulmonary fibrosis (IPF) 34.4%, hypersensitivity pneumonitis (HP) - 17.7%, idiopathic nonspecific interstitial pneumonitis (iNSIP) - 16.8%, connective tissue disease-associated ILD (CTD-ILD) - 16.3%, and sarcoidosis - 9.1%. Conclusion Idiopathic pulmonary fibrosis is the most prevalent ILD in Pakistan, followed by HP and iNSIP. An ongoing prospective registry with longitudinal follow-up will help us further elaborate on the clinical characteristics, treatment, and survival outcome of patients with ILD.

Eosinophilic lung disease as a sequela of MSSA pneumonia.

Eosinophilic lung diseases are a rare group of lung disorders with multiple known and unknown aetiologies and the diagnosis is often challenging. We present a case of a young man who was admitted with pneumonia due to methicillin-sensitive Staphylococcus aureus and was discharged on antibiotics. He presented to the emergency department approximately 2 weeks after discharge with high-grade fever, cough and shortness of breath associated with serum and bronchoalveolar lavage eosinophilia. He was then treated with steroids with complete resolution of disease process.

Sarcoidosis presenting as vocal cord palsy: an unusual presentation and literature review.

We report the case of a 60-year-old woman, presenting with left vocal cord paralysis (VCP). Diagnostic evaluation revealed sarcoidosis to be the underlying pathology. Computed tomography (CT) scans exhibited enlarged subcarinal, pretracheal, and prevascular lymph nodes as the possible mechanism of left VCP through compression of the left recurrent laryngeal nerve. Initial treatment with oral prednisolone and azathioprine led to remission of symptoms; however, tapering of dosage led to relapse of cough without any signs of VCP. The dosage of prednisolone was further boosted, leading to complete remission. A review of literature reveals 20 cases have been reported to date, with all but one involving the left vocal cord. This is the first reported case, with a relapse of the disease without a relapse of VCP, indicating the rarity of sarcoidosis-associated VCP.

Factors predicting in-hospital mortality among patients admitted with community acquired pneumonia at a tertiary care hospital Karachi, Pakistan.

INTRODUCTION: Community Acquired Pneumonia (CAP) is associated with significant morbidity and mortality globally, but unfortunately there is limited data available from South East Asia. OBJECTIVE: To determine the risk factors associated with in-hospital mortality in patients with CAP in a tertiary care hospital of Pakistan. METHODS: A retrospective study was conducted on adult patients admitted with a diagnosis of CAP from January 2011 till December 2016. Their clinical records were reviewed and a multivariable analysis was done to determine the factors associated with in-hospital mortality. RESULTS: A total of 1100 files were reviewed, of which 509 were included in the analysis. The mean age was 63.6 ± 16.5 years and 302 (52.16%) were males. The most Common isolated pathogen was Staphylococcus aureus (23%). Overall mortality was 10.8%. On univariate analysis factors associated with mortality were old age patients (P = 0.02); history of pneumonia in last 12 months (P = 0.008); CURB 65 score ≥ 3 (P < 0.001) and high dependency units as initial site of care (P < 0.001). On multivariable analysis CURB65 ≥ 3 score; high dependency unit as initial site of care; bedridden status; presence of bilateral infiltrates on chest X-ray and hemoglobin of 10.4 g/dL or less at the time of admission were key determinants of in-hospital mortality. CONCLUSION: We found CURB65 ≥ 3 score; high dependency unit as initial site of care; bedridden status; bilateral infiltrates on chest X-ray and low hemoglobin (10.4 g/dL or less) at the time of admission as independent risk factors of in-hospital mortality. Staphylococcus aureus was the most common organism isolated in patients.

Accuracy of genotype MTBDRplus line probe assay in patients with tuberculous pleural effusion: comparison with clinical and culture based diagnosis.

Background: Pleural tuberculosis (TB) diagnosis is challenging due to paucibacillary disease. Diagnostic accuracy of GenoType MTBDRplus Line Probe Assay (MTBDRplus) has been evaluated in this study for pleural TB diagnosis.Objective: To evaluate diagnostic accuracy of MTBDRplus for pleural TB diagnosis compared to clinical and microbiological diagnosis.Methods: This prospective study was conducted at the Aga Khan University, Pakistan. Pleural fluid from 203 suspected pleural TB patients was collected and tested for smear, culture and MTBDRplus. Diagnostic accuracy of MTBDRplus was determined using clinical diagnosis and culture as the gold standard.Results: Out of 203 TB suspect patients, MTBDRplus, culture and smear were positive in 14 (6. 9%), 27 (13.3%) and 4 (1.9%) cases, respectively. A total of 106/203 patients (27 culture positive and 79 culture negative) successfully completed TB treatment. Considering clinical diagnosis as gold standard, sensitivity of MTBDRplus was 13.2%; 95% CI (7.4-21.2%) and specificity was 100%; 95% CI (96.1-100%). The sensitivity and specificity of MTBDRplus in culture positive samples were 44.4%; 95% CI (25.5-64.7%) and 98.9%; 95% CI (95.9-99.9%), respectively. Excluding indeterminate results, MTBDRplus accurately detected isoniazid sensitivity in 5/6 and rifampicin sensitivity in 6/6 cases.Conclusion: MTBDRplus had a low sensitivity of 13.2% in clinically diagnosed and 44% in culture-confirmed pleural TB patients and therefore could not be included in most diagnostic algorithms. Due to a higher sensitivity than smear, MTBDRplus may have a role in tuberculous pleural effusion diagnosis if it is positive pending culture results and pleural biopsy.

Large mediastinal mass in a 15-year-old boy.

Hyperimmunoglobulin E syndrome is a rare multisystem inherited disorder characterised by high serum IgE levels, skin disorder causing eczema, dermatitis, recurrent staphylococcal infections and pulmonary infections and various skeletal and connective tissue abnormalities. Common presentation is with recurrent skin and sinopulmonary infections. Several features unrelated to immune system such as characteristic facial features, hyperextensibility of joints, multiple bone fractures and craniosynostosis have been described in the literature. We describe a rare presentation of this disease with invasive aspergillosis presenting as mediastinal mass with extension to mediastinal structures and pulmonary vasculature.

Granulomatosis with polyangiitis: a 17 year experience from a tertiary care hospital in Pakistan.

OBJECTIVE: Granulomatosis with Polyangiitis (GPA) is an autoimmune, multi-system, small and medium vessel vasculitis with granulomatous inflammation. Aim of this study was to assess the clinical and radiological presentations of patients with GPA amongst the Pakistani population. It is a single centre retrospective single observation study. RESULTS: Study was conducted at the Aga Khan University Hospital, Karachi with records were reviewed from January 2000 to December 2017. Definitive diagnosis was made using a combination of serological anti-neutrophil cytoplasmic antibody (ANCA) testing along with the clinical and radiological presentation. A total of 51 patients met the diagnostic criteria in the time frame of the study. There were 23 males and 28 females with mean age of 44.0 ± 17.8 years on presentation. Arthritis was the most common symptom present in 41.2% of the cases followed by cough in 32.0%. Sixteen patients showed pulmonary infiltrates on chest X-ray. C-ANCA was positive in all of the patients compared with 21.6% p-ANCA positivity. A total of 13 biopsies were done. The median Birmingham Vasculitis Activity Score was 12. We report a 17.6% mortality rate with 5 deaths occurring due to respiratory failure. GPA is a diagnostic challenge leading to late diagnosis which can contribute to significant morbidity and mortality specially in the Third World.

Neurological involvement associated with Plasmodium vivax malaria from Pakistan.

Plasmodium vivax is the most common specie causing malaria outside Africa with approximately 13.8 million reported cases worldwide. We report case of P. vivax infection with cerebral involvement. A nine year old boy presented with high grade fever accompanied by projectile vomiting and abnormal behavior later he developed seizures, shock, and unconsciousness. P. vivax monoinfection was diagnosed based on peripheral smears and PCR. After antimalarial therapy, patient made full recovery. Current case highlights increasing trend of cerebral complications caused by P. vivax.

Clinical characteristics and factors associated with mortality in idiopathic pulmonary fibrosis: An experience from a tertiary care center in Pakistan.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) that predominantly affects older adults. IPF has the highest mortality burden of all ILDs. Data on mortality in patients with IPF is limited in developing countries. OBJECTIVES: To identify factors associated with mortality in patients with IPF at a tertiary care center in Pakistan. METHODS: A retrospective chart review was conducted at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan from January 2005 to December 2015. Patients were assessed for smoking status, clinical onset of disease, pulmonary hypertension, disease severity based on spirometry and hypoxemia. RESULTS: A total of 239 cases were reviewed, of which 103 were non-survivors. A total of 45 (18%) were current smokers and 71 (29.7%) were ex-smokers. Smoking was more common in non-survivors (56.3% P ≤ .01). Pulmonary hypertension was present in 18.8% of patients. 95.4% of patients who had received pirfenidone treatment were alive at the time of study. On multivariate analysis, pirfenidone treatment (OR 0.03; 95% CI 0.01-0.08), current smoking (OR 2.60; 95% CI 1.04-6.58), age older than 60 years (OR 2.63; 95% CI 1.04-6.58) and hypoxemia (OR 3.29; 95% CI 1.58-6.84) were the factors associated with mortality. CONCLUSION: Smoking, age greater than 60 years and hypoxemia were identified as factors that increased the odds of mortality in IPF patients, whereas pirfenidone was found to lower the odds of mortality.

Association of hypercapnia on admission with increased length of hospital stay and severity in patients admitted with community-acquired pneumonia: a prospective observational study from Pakistan.

OBJECTIVE: To determine whether the presence of hypercapnia on admission in adult patients admitted to a university-based hospital in Karachi, Pakistan with community-acquired pneumonia (CAP) correlates with an increased length of hospital stay and severity compared with no hypercapnia on admission. STUDY DESIGN: A prospective observational study. SETTINGS: Tertiary care hospital in Karachi, Pakistan. METHODS: Patients who met the inclusion criteria were enrolled in the study. The severity of pneumonia was assessed by CURB-65 and PSI scores. An arterial blood gas analysis was obtained within 24 hours of admission. Based on arterial PaCO2 levels, patients were divided into three groups: hypocapnic (PaCO2 <35 mm Hg), hypercapnic (PaCO2 >45 mm Hg) and normocapnic (PaCO2 <35-45 mm Hg). OUTCOMES: The primary outcome was the association of hypercapnia on admission with mean length of hospital stay. Secondary outcomes were the need for mechanical ventilation, ICU admission and in-hospital mortality. RESULTS: A total of 295 patients of mean age 60.20±17.0 years (157 (53.22%) men) were enrolled over a 1-year period. Hypocapnia was found in 181 (61.35%) and hypercapnia in 57 (19.32%) patients. Hypercapnic patients had a longer hospital stay (mean 9.27±7.57 days), increased requirement for non-invasive mechanical ventilation (NIMV) on admission (n=45 (78.94%)) and longer mean time to clinical stability (4.39±2.0 days) compared with the other groups. Overall mortality was 41 (13.89%), but there was no statistically significant difference in mortality (p=0.35) and ICU admission (p=0.37) between the three groups. On multivariable analysis, increased length of hospital stay was associated with NIMV use, ICU admission, hypercapnia and normocapnia. CONCLUSION: Hypercapnia on admission is associated with severity of CAP, longer time to clinical stability, increased length of hospital stay and need for NIMV. It should be considered as an important criterion to label the severity of the illness and also a determinant of patients who will require a higher level of hospital care. However, further validation is required.

Coinfection with Lichtheimia corymbifera and Aspergillus flavus in an Immune-Competent Patient Mimicking as Pulmonary-Renal Syndrome.

Lichtheimia corymbifera and Aspergillus flavus pulmonary coinfection has been rarely reported in immune-competent patients. We report case of a young male who presented with clinical features of pulmonary-renal syndrome and was later diagnosed to have bilateral polymicrobial fungal lung infection.