Prevalence, Clinical Characteristics and Determinants of Unsuccessful Treatment Outcomes Among Pulmonary Tuberculosis Patients: A 5-Year Registry-Based Retrospective Cohort Study

Hind M AlOsaimi,1 Mohammed K Alshammari,2 Ghadah K Almijlad,3 Nawaf M Alotaibi,3 Dhafer A Alqahtani,4 Mohammed M Alshamrani,5 Tariq A Shutur,6 Mansior F Alhazmi,6 Mohammed A Hurubi,6 Kutayd S ALShammari,6 Khalid M Alzahrani,7 Hadeel M Aldaghriri,7 Anood A Alshammari,8 Oudah S Alatawi,8 Reema A Alharbi9 1Department of Pharmacy Services Administration, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia; 2Department of Clinical Pharmacy, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia; 3Department of Clinical Pharmacy, Northern Border University, Rafha, Kingdom of Saudi Arabia; 4Department of Pharmacy, Security Forces Hospital, Riyadh, Kingdom of Saudi Arabia; 5Department of Respiratory Care, Northern Armed Area Forced Hospital, Hafar al Batin, Kingdom of Saudi Arabia; 6Department of Supply and Logistics, Northern Armed Area Forced Hospital, Hafar Al Batin, Kingdom of Saudi Arabia; 7Department of Radiology, Northern Armed Area Forced Hospital, Hafar Al Batin, Kingdom of Saudi Arabia; 8Pharmaceutical Services Department, Northern Area Armed Forces Hospital, King Khalid Military, Hafr Al Batin, Kingdom of Saudi Arabia; 9Department of Medicine, University of Tabuk, Tabuk, Saudi ArabiaCorrespondence: Mohammed K Alshammari, Department of Clinical Pharmacy, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia, Email [email protected]: Despite the existence of effective medications, pulmonary tuberculosis (PTB) remains a significant global public health concern, The evaluation and feedback of national TB control programs are crucial, requiring diligent monitoring of TB treatment outcomes and analysis of the factors influencing these outcomes. This study aims to provide valuable insights into the challenges faced by TB patients, which can inform better strategies for treatment and management in the future.Patients and Methods: We conducted a study in King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia (KSA), from January 1, 2018 to December 31, 2023. The study was a registry-based retrospective cohort study. Patients’ data were sourced from the National Tuberculosis Registry database of Saudi Arabia. Treatment outcomes were determined as either success or failure, considering clinical evaluation, changes in chest X-rays, and the results of subsequent sputum examinations during follow-up. To evaluate the data, SPSS version 28.0 was used.Results: A total of 427 PTB patients participated in the study. The results show successful treatment outcomes among 88.5% of patients. Among the patients, males exhibited a higher likelihood of treatment failure as compared to females (aOR 1.3; 95%Cl 1.2– 1.5, p < 0.001). Patients with positive sputum smear (aOR 1.3; 95%Cl 1.1– 1.3 p < 0.00) and the presence of cough were associated with an increased risk of treatment failure (aOR1.5; 95%Cl 1.1– 1.4, p < 0.001).Conclusion: This study shows that the percentage of unsuccessful treatment outcomes is high, ie, 11.5%, due to patients’ deaths and loss to follow-up. Enhanced supervision and treatment monitoring for tuberculosis patients at high risk of treatment failure can lead to improved treatment success rates in Saudi Arabia.Keywords: tuberculosis, treatment outcomes, retrospective study, Saudi Arabi

Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2)

BACKGROUND Deficiency of adenosine deaminase 2 (DADA2) is a syndrome with pleiotropic manifestations including vasculitis and hematologic compromise. A systematic definition of the relationship between ADA2 mutations and clinical phenotype remains unavailable. OBJECTIVE We tested whether the impact of ADA2 mutations on enzyme function correlates with clinical presentation. METHODS DADA2 patients with severe hematologic manifestations were compared with vasculitis-predominant patients. Enzymatic activity was assessed using expression constructs reflecting all 53 missense, nonsense, insertion and deletion genotypes from 152 patients across the DADA2 spectrum. RESULTS We identified DADA2 patients presenting with pure red cell aplasia (PRCA, n = 5) or bone marrow failure syndrome (BMF, n = 10). Most patients did not exhibit features of vasculitis. Recurrent infection, hepatosplenomegaly and gingivitis were common in patients with BMF, of whom half died from infection. Unlike DADA2 patients with vasculitis, patients with PRCA and BMF proved largely refractory to tumor necrosis factor inhibitors. ADA2 variants associated with vasculitis predominantly reflected missense mutations with at least 3% residual enzymatic activity. By contrast, PRCA and BMF were associated with missense mutations with minimal residual enzyme activity, nonsense variants, and insertions / deletions resulting in complete loss of function. CONCLUSION Functional interrogation of ADA2 mutations reveals an association of subtotal function loss with vasculitis, typically responsive to TNF blockade, whereas more extensive loss is observed in hematologic disease which may be refractory to treatment. These findings establish a genotype-phenotype spectrum in DADA2

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection

Patterns of psychotropic medication use in inpatient and outpatient psychiatric settings in Saudi Arabia

Fahad D Alosaimi,1 Abdulhadi Alhabbad,2 Mohammed F Abalhassan,3 Ebtihaj O Fallata,4 Nasser M Alzain,5 Mohammad Zayed Alassiry,6 Bander Abdullah Haddad71Department of Psychiatry, King Saud University, Riyadh, 2Department of Psychiatry, Prince Mohammed Medical City, Aljouf, 3Department of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, 4Department of Psychiatry, Mental Health Hospital, Jeddah, 5Department of Psychiatry, Al-Amal Complex for Mental Health, Dammam, 6Medical Services Department, Abha Psychiatric Hospital, Abha, 7Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard, Riyadh,&nbsp;Saudi ArabiaObjective: To study the pattern of psychotropic medication use and compare this pattern between inpatient and outpatient psychiatric settings in Saudi Arabia.Method: This cross-sectional observational study was conducted between July 2012 and June&nbsp;2014 on patients seeking psychiatric advice at major hospitals in five main regions of Saudi Arabia. Male (n=651) and female (n=594) patients who signed the informed consent form and were currently or had been previously using psychotropic medications, irrespective of the patient&rsquo;s type of psychiatric diagnosis and duration of the disease, were included. A total of 1,246 patients were found to be suitable in the inclusion criteria of whom 464 were inpatients while 782 were outpatients.Results: Several studied demographic factors have shown that compared with outpatients, inpatients were more likely to be male (P=0.004), unmarried (P&lt;0.001), have less number of children (1&ndash;3; P=0.002), unemployed (P=0.001), have a lower family income (&lt;3,000 SR; P&lt;0.001), live in rural communities (P&lt;0.001), have a lower body mass index (P=0.001), and are smokers (P&lt;0.001); however, there were no differences with regard to age or educational levels. The current frequency of use of psychotropic medications in overall patients was antipsychotics (76.6%), antidepressants (41.4%), mood stabilizers (27.9%), and antianxiety (6.2%). However, compared to outpatients, the current use of medications for inpatients was more frequent (93.8% vs 89.9%, P=0.019) with inpatients more likely to be treated with multiple medications (2.1 vs 1.8 medications). A similar trend was observed in the case of antipsychotics, high potency first-generation antipsychotics, second-generation antipsychotics, mood stabilizers, and antianxiety medicines where inpatients were more frequently treated with these medications for all psychiatric diagnoses when compared with outpatients. On the contrary, in the case of antidepressant treatment, an opposite trend was observed with more number of treated outpatients in comparison to inpatients. Among elderly patients, 75.9% received antipsychotics, mainly second-generation formulations (67.2%), whereas only 41% received antidepressants and 13.8% received mood stabilizers.Conclusion: Based upon the present study data, it is concluded that among all the psychotropic medications, antipsychotics were heavily used and the frequency was found to be significantly high in the case of inpatients compared with outpatients. Such a practice may lead to multiple negative consequences among the Saudi psychiatric patient population. Further, extensive use of sodium valproate in the case of bipolar disorder, and also among females either in childbearing age or during pregnancy is also the cause of concern and warrants logical use. Overall, this study may help in assessing the burden of psychiatric illness within specific patient demographics and might be effectively used to strategically plan health resources allocation, generate new treatment hypothesis, or be used as a source of evidence that could further integrate other observational studies.Keywords: psychotropic, inpatient, outpatient, antipsychotics, antidepressants, mood stabilizers, Saudi Arabi