Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.

Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting.

A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam.

Changes in antimicrobial resistance and outcomes of health care-associated infections.

To describe the change in the epidemiology of health care-associated infections (HAI), resistance and predictors of fatality we conducted a nationwide study in 24 hospitals between 2015 and 2018. The 30-day fatality rate was 22% in 2015 and increased to 25% in 2018. In BSI, a significant increasing trend was observed for Candida and Enterococcus. The highest rate of 30-day fatality was detected among the patients with pneumonia (32%). In pneumonia, Pseudomonas infections increased in 2018. Colistin resistance increased and significantly associated with 30-day fatality in Pseudomonas infections. Among S. aureus methicillin, resistance increased from 31 to 41%.

Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 in vitro.

Ribavirin is a guanosine analog with broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico, and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection, whereas the drug itself did not show any toxic effect over the concentration range tested. In silico analysis suggested that ribavirin has a broad-spectrum impact on SARS-CoV-2, acting at different viral proteins. According to the detailed molecular techniques, ribavirin was shown to decrease the expression of TMPRSS2 at both mRNA and protein levels 48 h after treatment. The suppressive effect of ribavirin in ACE2 protein expression was shown to be dependent on cell types. Finally, proteolytic activity assays showed that ribavirin also showed an inhibitory effect on the TMPRSS2 enzyme. Based on these results, we hypothesized that ribavirin may inhibit the expression of TMPRSS2 by modulating the formation of inhibitory G-quadruplex structures at the TMPRSS2 promoter. As a conclusion, ribavirin is a potential antiviral drug for the treatment against SARS-CoV-2, and it interferes with the effects of TMPRSS2 and ACE2 expression.

Is pulse oximeter a reliable tool for non-critically ill patients with COVID-19?

INTRODUCTION: Guidelines recommend using a pulse oximeter rather than arterial blood gas (ABG) for COVID-19 patients. However, significant differences can be observed between oxygen saturation measured by pulse oximetry (SpO2 ) and arterial oxygen saturation (SaO2 ) in some clinical conditions. We aimed to assess the reliability of the pulse oximeter in patients with COVID-19. METHODS: We retrospectively reviewed ABG analyses and SpO2 levels measured simultaneously with ABG in patients hospitalised in COVID-19 wards. RESULTS: We categorised total 117 patients into two groups, in whom the difference between SpO2 and SaO2 was ≤4% (acceptable difference) and >4% (large difference). A large difference group exhibited higher neutrophil count, C-reactive protein, ferritin, fibrinogen, D-dimer and lower lymphocyte count. Multivariate analyses revealed that increased fibrinogen, increased ferritin and decreased lymphocyte count were independent risk factors for a large difference between SpO2 and SaO2 . The total study group demonstrated the negative bias of 4.02% with the limits of agreement of -9.22% to 1.17%. The bias became significantly higher in patients with higher ferritin, fibrinogen levels and lower lymphocyte count. CONCLUSION: Pulse oximeters may not be sufficient to assess actual oxygen saturation, especially in COVID-19 patients with high ferritin and fibrinogen levels and low lymphocyte count with low SpO2 measurements.

Ceftazidime - Avibactam susceptibility among carbapenem-resistant Enterobacterales in a pilot study in Turkey.

This study aimed to detect carbapenemase genes and to determine the in vitro susceptibility of Ceftazidime-Avibactam (CZA) in Enterobacterales isolates. Carbapenemase genes were detected by polymerase chain reaction. CZA sensitivity of isolates was evaluated with broth microdilution (BMD) and disk diffusion methods. A total of 318 carbapenem-resistant Enterobacterales isolates were included. Most of the isolates (n = 290, 91.2%) were identified as Klebsiella pneumoniae. The most common carbapenemase type was OXA-48 (n = 82, 27.6%). CZA susceptibility was evaluated in 84 isolates with OXA-48 and KPC carbapenemase activity. Both BMD and disk diffusion methods revealed that 95.2% of the isolates were sensitive to CZA; whereas, 4 (4.76%) isolates were resistant to CZA. Among colistin resistant isolates, 96.5% (n = 80) of them were susceptible to CZA. Our study demonstrated high in vitro efficacy of CZA in Enterobacterales isolates producing OXA-48 carbapenemase. High susceptibility rates against colistin resistant isolates which generally are also pan drug resistant, makes CZA a promising therapeutic choice for difficult-to-treat infections. Due to its high correlation with the BMD, disk diffusion method is a suitable and more practical method in detecting CZA in vitro activity.

Pattern of systemic antibiotic use and potential drug interactions: Evaluations through a point prevalence study in Ankara University Hospitals.

Background/aim: Most of the hospitalized patients are on a number of drugs for comorbidities and/or to prevent nosocomial infections. This necessitates a careful consideration of drug interactions not only to avoid possible toxicities but also to reach the highest efficiency with drug treatment. We aimed to investigate drug interactions related to systemic antibiotic use and compare three different databases to check for drug interactions while characterizing the main differences between medical and surgical departments. Materials and methods: This point prevalence study covered data on 927 orders for patients hospitalized between June 3 and 10, 2018 in Ankara University Hospitals. Systemic antibiotic use and related drug interactions were documented using UptoDate, Drugs, and Medscape and comparisons between the departments of medical and surgical sciences were made. Results: The number of orders, or the number of drugs or antibiotics per order were not different between the medical and surgical sciences departments. A total of 1335 antibiotic-related drug interactions of all levels were reported by one, two, or all three databases. UptoDate reported all common and major interactions. Pantoprazole was the most commonly prescribed drug and appeared in 63% of all orders. Among 75 different molecules, ceftriaxone and meropenem were the two most prescribed antibiotics by the surgical and medical departments, respectively. Conclusion: A dramatic variance existed amongst antibiotics prescribed by different departments. This indicated the requirement for a centralized role of an infectious diseases specialist. Especially for the hospitalized patient, prophylactic coverage with at least one antibiotic brought about a number of drug interactions. A precise evaluation of orders in terms of drug interactions by a clinical pharmacist (currently none on duty) will reduce possible drug-related hazards.

Stage I-laparoscopy partial ALPPS procedure for perihilar cholangiocarcinoma.

The treatment for perihilar cholangiocarcinoma (PHC) is a challenge for the surgeon requiring complex resections with a reported perioperative mortality rate between 15% and 48%. In PHC patients with future liver remnant (FLR) less than 30%, it is advised that hepatectomy can be safely performed after the FLR is modified. Associating Liver Partition and Portal vein ligation for Staged Hepatectomy (ALPPS) procedure is criticized heavily due to its high morbidity and mortality rate in this setting. Hereby, we are reporting a modification of ALPPS procedure for PHC. Clinical presentation, preoperative work-up as well as operation and postoperative course of two cases were described in detail. Both patients were jaundiced preoperatively, stage 1 partial-ALPPS procedures were performed laparoscopically, there was sufficient remnant hypertrophy during the interval stage and there was no posthepatectomy liver failure after the second stage (Supporting Information Video). We have followed patients with a mean follow up of 35 months without any recurrence. Here we describe the key technical aspects of this approach that are discussed in three parts: minimally invasive first stage, biliary drainage of both FLR, and deportalized liver at first stage and biliary reconstruction at the second stage. This technique, in selected patients, can extend the indication of ALPPS procedure for PHC with preoperative jaundice.

Regulatory consideration on preparation and clinical use of COVID-19 convalescent plasma.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), spreading from Wuhan to worldwide has been emerged since December 2019. Although scientists and researchers have been racing to develop specific therapeutic agents or vaccines against SARS-CoV-2 since the identification of the agent, either a drug or a vaccine has not been approved to treat or to prevent COVID-19 up to date. On the base of historical experiences, Convalescent Plasma (CP), a passive antibody therapy, has been evaluated as a hopeful and potential therapeutic option since the beginning of the COVID-19 outbreak. Immune plasma had been used previously for the treatment of H1N1 influenza virus, SARS-CoV-1 and MERS-CoV epidemics successfully. In this scope competent authorities are responsible to set up certain principles and criteria for the collection and clinical use of COVID-19 Convalescent Plasma (CCP). This document has been prepared to aid both for the convalescent plasma suppliers and the clinicians. The first part encompasses the supply of CCP and the second part lead the clinical use of CCP for the treatment of patients with severe COVID-19 infection. Turkish Ministry of Health developed a guide on collection and clinical use of CCP and created a web-based monitoring system to follow-up the patients treated with convalescent plasma in universal. This follow-up process is thought to be crucial for the creation and development of current and future treatment modalities. This guide would be a pathfinder for clinicians and/or institutions those eager to conduct CCP treatment more effectively.

Clinical course of COVID-19 infection in elderly patient with melanoma on nivolumab.

Outbreak of the new type coronavirus infection, known as coronavirus infection 2019 (COVID-19), has begun in December 2019, in Wuhan, China. As of today, 3 April 2020, 972,640 people affected and 50,325 people died from Severe Acute Respiratory Syndrome-Coronavirus 2. There is not any standard treatment for coronavirus infection 2019; however, there are promising data for hydroxychloroquine and some anti-retroviral drugs. Programmed death-1 (PD-1)/programmed death ligand-1 (PDL-1) pathway is an important target for the cancer immunotherapy. However, there is a robust pre-clinical and clinical data regarding inhibitor effect of this pathway on the acute or chronic viral infections. Thus, blockade of this pathway may lead to an anti-viral effect and decrease viral load. Here, we report the clinical course of coronavirus infection 2019 infection of a patient in whom older aged, having multiple co-morbidities, and taking nivolumab for metastatic malignant melanoma. In contrast to her older age, comorbidities, and cancer diagnosis, she was in a good condition, and there was also no pneumonia finding. We think that this good clinical course of coronavirus infection 2019 infection may be related to blockade of PD-1/PDL-1 pathway with nivolumab. It is impossible to say that blockade of PD-1/PDL-1pathway is a treatment option for COVID-19; however, we want to share our experience.

[Management of obstructive sleep apnea during COVID-19 pandemic]. / COVID-19 pandemisi sirasinda obstrüktif uyku apne yönetimi.

Coronavirus disease 2019 (COVID-19) is an infectious disease that causes important mortality and morbidity all over the world caused by SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), which started in China at the end of 2019. It spreads rapidly, mainly through droplets, and especially for all healthcare workers involved in aerosol producing procedures are at high risk. During COVID-19 pandemic , the health systems worldwide, along with the practice of chest diseases daily were affected. In our article, we aimed to give some clinical suggestions related to sleep practices according to current data.

Medical mask or N95 respirator: When and how to use?

COVID-19 pandemic is now a global threat to human health reaching up to 2 million infected people all around the world. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipment, especially masks, has been among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.

Impact of the ST101 clone on fatality among patients with colistin-resistant Klebsiella pneumoniae infection.

Objectives: We describe the molecular characteristics of colistin resistance and its impact on patient mortality. Methods: A prospective cohort study was performed in seven different Turkish hospitals. The genotype of each isolate was determined by MLST and repetitive extragenic palindromic PCR (rep-PCR). Alterations in mgrB were detected by sequencing. Upregulation of pmrCAB, phoQ and pmrK was quantified by RT-PCR. mcr-1 and the genes encoding OXA-48, NDM-1 and KPC were amplified by PCR. Results: A total of 115 patients diagnosed with colistin-resistant K. pneumoniae (ColR-Kp) infection were included. Patients were predominantly males (55%) with a median age of 63 (IQR 46-74) and the 30 day mortality rate was 61%. ST101 was the most common ST and accounted for 68 (59%) of the ColR-Kp. The 30 day mortality rate in patients with these isolates was 72%. In ST101, 94% (64/68) of the isolates had an altered mgrB gene, whereas the alteration occurred in 40% (19/47) of non-ST101 isolates. The OXA-48 and NDM-1 carbapenemases were found in 93 (81%) and 22 (19%) of the total 115 isolates, respectively. In multivariate analysis for the prediction of 30 day mortality, ST101 (OR 3.4, CI 1.46-8.15, P = 0.005) and ICU stay (OR 7.4, CI 2.23-29.61, P = 0.002) were found to be significantly associated covariates. Conclusions: Besides ICU stay, ST101 was found to be a significant independent predictor of patient mortality among those infected with ColR-Kp. A significant association was detected between ST101 and OXA-48. ST101 may become a global threat in the dissemination of colistin resistance and the increased morbidity and mortality of K. pneumoniae infection.

Diagnosis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Turkish Expert Opinion (TEO-2).

One of the most problematic issues in hematological malignancies is the diagnosis of invasive fungal diseases. Especially, the difficulty of mycological diagnosis and the necessity of immediate intervention in molds have led to the adoption of "surrogate markers" that do not verify but rather strongly suggest fungal infection. The markers commonly used are galactomannan (GM), beta-glucan, and imaging methods. Although there are numerous studies on these diagnostic approaches, none of these markers serve as a support for the clinician, as is the case in human immunodeficiency virus (HIV) or cytomegalovirus (CMV) infections. This paper has been prepared to explain the diagnostic tests. As molecular tests have not been standardized and are not used routinely in the clinics, they will not be mentioned here.

Treatment initiation rates of patients with positive anti-hepatitis C virus results in tertiary hospitals in Turkey.

INTRODUCTION: The aim of this national, multicenter, cross-sectional, retrospective chart review study was to determine the proportion of patients in Turkey who received hepatitis C virus (HCV) treatment after receiving positive anti-HCV results during HCV screening. METHODOLOGY: Data related to patients' demographics, laboratory results, time interval from obtaining a positive anti-HCV result to treatment initiation, specialty of the physician requesting anti-HCV screening, and type of hospital were analyzed. RESULTS: Among 1,000 patients who received a positive anti-HCV result, 50.3% were male and 78.5% were screened for HCV-RNA. Among HCV-RNA screened patients, 54.8% (n = 430) had a positive result. Among patients who tested positive for HCV-RNA, 72.8% received HCV treatment in line with their positive anti-HCV results. The median time from obtaining a positive anti-HCV result to initiation of HCV treatment was 91.0 days (interquartile range 42.0 to 178.5). Non-surgical branches requested HCV-RNA testing more frequently than surgical branches (p < 0.001). The rate of access to HCV treatment was higher among patients screened in university hospitals than among patients screened in training and research hospitals (p < 0.001). CONCLUSIONS: Our results indicate a higher rate of treatment initiation among patients with HCV infection than is described in the published literature. Furthermore, the time from screening to treatment initiation was considerably shorter compared with other international studies. However, since HCV-RNA testing was not requested in a significant portion of patients with a positive anti-HCV test result, there might be a large patient population with HCV who do not receive treatment.

Herpes Zoster Burden of Disease and Clinical Management in Turkey: A Comprehensive Literature Review.

INTRODUCTION: Herpes zoster (HZ), or shingles, is caused by the reactivation of varicella zoster virus (VZV) and typically presents as an acute, painful dermatomal rash, but can lead to long-term, distressing complications such as postherpetic neuralgia (PHN). Increasing trends in HZ cases are evident globally among the aging population; however, reviews investigating the epidemiology and clinical management of HZ in Turkey are lacking. Therefore, a literature review of local studies in Turkey was conducted to identify the data available and identify gaps in the literature. METHODS: Literature searches were carried out in PubMed and local journals to retrieve published articles that reported surveillance data, seroepidemiology, patient outcomes, or clinical management related to HZ or VZV in Turkey until April 30, 2022. Studies included primary data reports, case studies, secondary data reviews, and epidemiological studies in healthy or at-risk populations; HZ was the primary focus of the review. RESULTS: No studies reported VZV or HZ epidemiological data at a national level. One large retrospective study in Istanbul reported that HZ incidence rates significantly increased in adults 18-44 years of age between 2011 and 2019. Four single-center studies reported the proportion of dermatological patients with HZ at 0.43-1.56%. PHN was the most common reported complication, occurring in 8-58.9% of patients with HZ. However, out of 39 identified case reports, HZ ophthalmicus was the most frequently reported complication. Two studies highlighted poor disease awareness and risk perception of HZ among Turkish citizens. CONCLUSION: Overall, there were limited comprehensive epidemiological data on HZ in Turkey. However, the abundance of case studies on HZ complications indicates a strong disease presence and diverse clinical management in Turkey. Further research will be important to understand the impact of HZ, increase disease awareness, and support the introduction of new preventative strategies.

The Present and Future Aspects of Life-Long Pertussis Prevention: Narrative Review with Regional Perspectives for Türkiye.

Pertussis, caused by Bordetella pertussis, remains one of the most widespread, contagious, and vaccine-preventable diseases. It results in notable morbidity and mortality as well as severe medical, social, and economic burden. Despite high global vaccine coverage, pertussis continues to be a significant epidemiologic problem, with outbreak episodes every few years just as in the pre-vaccination era. In Türkiye, there is a lack of comprehensive data on the current burden of pertussis in different age and risk groups, leading to underdiagnosis and underreporting of the disease, especially in adults who are often not considered at risk. Available data from Türkiye also reveal inadequate levels of protective antibodies in preterm newborns, emphasizing the need for additional preventive measures. Authors stated that improving physician awareness of pertussis symptoms in patients with prolonged cough, increasing access to routine pertussis tests, and conducting surveillance studies would aid in accurate diagnosis and reporting in Türkiye. As the Turkish Ministry of Health Antenatal Care Management Guide suggests routine second and third pregnancy check-up visits at weeks 18-24 and 28-32 correspondingly, this period can be considered the ideal vaccination time for Türkiye. Introducing a booster dose of Tdap at around 10 years of age or during national military service would reduce transmission and protect susceptible individuals. Identifying individuals at high risk of severe pertussis and prioritizing them for a booster dose is also crucial in Türkiye. Enhancing surveillance systems, increasing healthcare professionals' awareness through training, and organizing catch-up visits for missed vaccinations during the COVID-19 pandemic are mentioned as additional strategies to improve pertussis prevention in Türkiye. This review focuses on the global and regional burden of pertussis and obstacles to effective prevention and evaluates existing strategies to achieve lifelong pertussis prevention. Literature and current strategies were also discussed from a Turkish national standpoint.

Recovery from Respiratory Failure in Patients with Coronavirus Disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can cause hypoxic respiratory failure; long-term oxygen therapy (LTOT) duration is unknown. MATERIAL AND METHODS: The aim was to investigate which patients would need LTOT after COVID-19 pneumonia. This single-center, prospective study was conducted at the Ankara University Faculty of Medicine, Department of Chest Diseases, between May 2021 and December 2021. The 70 patients hospitalized for COVID-19 pneumonia and discharged with LTOT due to hypoxemic respiratory failure were included. Patients were divided into 2 groups as group I (LTOT requirement <3 months) and group II (LTOT requirement continued ≥3 months). RESULTS: The mean age was 64.4 ± 13.5 years, and 44 (62.9%) of them were male. The most frequently encountered comorbidities were cardiovascular disease (57.1%) and lung disease (22.9%). While PaO2 levels increased in both groups during the follow-up period, this increment was significantly higher in group I (PaO2: 66.6 ± 9.9 mm Hg, P < .001). The factors affecting the LTOT requirement were evaluated using binary logistic regression. On multivariate analyses of lymphocytes, ferritin, C-reactive protein, PaO2, SaO2, subpleural reticulation, and number of lobes affected (≥3 lobes), the SaO2 level and presence of subpleural reticulation were significantly different between the 2 groups [odds ratio (OR) (95% CI): 0.853 (0.749-0.971), P = .016] and [OR (95% CI): 0.171 (0.042-0.733), P = .017], respectively. CONCLUSION: A significant proportion of patients who develop respiratory failure due to COVID-19 recover within the first 3 months. Factors determining the LTOT requirement for more than 3 months were SaO2 and the presence of subpleural reticulation.