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BackgroundOscillatory positive expiratory pressure (OPEP) devices are intended to facilitate sputum clearance and reduce cough, but there is limited evidence for their effectiveness in COPD, or to guide patient selection. We aimed to assess the impact of OPEP therapy on quality of life and objective measures of cough and sleep disturbance in patients with COPD with regular sputum production.MethodsWe enrolled stable patients with COPD, who reported sputum production every day or most days, into an assessor-blind, parallel-group, randomised controlled trial comparing 3 months of using an Acapella device against usual care (including use of the active cycle of breathing technique). The primary outcome was cough-related quality of life measured using the Leicester Cough Questionnaire (LCQ). Secondary outcomes included fatigue (Functional Assessment of Chronic Illness Therapy, FACIT score) and generic quality of life (EuroQol-5 Dimensions, EQ-5D). In a substudy (n=45), objective monitoring of cough and disturbance/movement during sleep were also available.Results122 participants (61/61 OPEP/control) were recruited, 40% female, 17% smokers, FEV1 38 (25–56)% predicted, and age 62±10 years. 103 completed the study (55/48 OPEP/control). Use of OPEP was associated with an improvement in LCQ compared with controls; MD (95% CI) 1.03 (0.71 to 2.10); (p=0.03), FACIT score 4.68 (1.34 to 8.02); (p<0.001) and EQ-5D 4.00 (0.49 to 19.75); (p=0.04). There was also an improvement in cough frequency −60 (−43 to −95) coughs/24 hours (p<0.001), but no statistically significant effect on sleep disturbance was identified.ConclusionsRegular use of an Acapella device improves symptoms and quality of life in people with COPD who produce sputum daily or most days.Trial registration number ISRCTN44651852.

The paucity of data on glycogen storage diseases (GSDs) from Arabs prompted us to report on hepatic GSD to characterize its clinical and molecular features and outcomes among Saudi children and to evaluate genotype‒phenotype correlations. We retrospectively reviewed the charts of 65 children (37 females) with genetically confirmed hepatic GSD who presented between 2008 and 2020 and were followed up for a median duration of 9 years (range: 0.4-21 years). The most common hepatic GSD in our cohort was GSD Ia (37%), followed by GSD III (20%), GSD Ib (12.3%), and GSDVI (10.8%). Twenty-seven variants were identified (8 novel and 4 from the common ancestor, i.e., \"founder in nature\"). The most common founder variant is P.(Arg83Cys) in the G6PC1 gene (20% of the 65 GSD patients), clustering in Aseer Province. Six patients underwent liver transplantation (due to difficulty controlling hypoglycemia in 5 GSD Ia patients and severe portal hypertension in one GSD IV patient). One patient with GSD type 1b developed hepatic adenoma at the age of 17 years. A patient with GSD IXc developed portal hypertension at the age of 5 years, and one patient with GSD IXa developed cirrhosis. Renal complications developed in 18 patients. An echocardiogram was performed in 16 patients and revealed mild-moderate asymptomatic left ventricular hypertrophy in 5 patients. The majority of the hepatic GSD cases in our cohort manifested a severe phenotype (hepatomegaly, hypoglycemia, ± systemic involvement); only the 7 GSD VI patients manifested a mild phenotype (hepatomegaly without hypoglycemia). No \"genotype‒phenotype correlations\" could be observed when the two common G6PC1 gene variants [p.(Arg83Cys) versus p.(Gln20Arg)] were compared. With the exception of GSD VI, all the hepatic GSD subtypes in Saudi Arabia are associated with a severe phenotype. Identification of the predominant gene variants and their geographic distribution in any population is likely to facilitate rapid molecular analysis by future targeting of that specific mutation.

(1) Background and Objectives: Pneumonia is a major cause of morbidity and mortality worldwide, including in Saudi Arabia, and the prevalence and etiology of the disease varies depending on the setting. The development of effective strategies can help reduce the adverse impact of this disease. Therefore, this systematic review was conducted to explore the prevalence and etiology of community-acquired and hospital-acquired pneumonia in Saudi Arabia, as well as their antimicrobial susceptibility. (2) Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations were followed for this systematic review. Several databases were used to perform a thorough literature search, and papers were then assessed for eligibility by two independent reviewers. The Newcastle-Ottawa Scale (NOS) was used to extract the data from the relevant research and evaluate its quality. (3) Results: This systematic review included 28 studies that highlighted the fact that gram-negative bacteria, particularly Acinetobacter spp. and Pseudomonas aeruginosa, were the common cause of hospital-acquired pneumonia, while Staphylococcus aureus and Streptococcus spp. were responsible for community-acquired pneumonia in children. The study also found that bacterial isolates responsible for pneumonia showed high resistance rates against several antibiotics, including cephalosporins and carbapenems. (4) Conclusions: In conclusion, the study found that different bacteria are responsible for community- and hospital-acquired pneumonia in Saudi Arabia. Antibiotic resistance rates were high for several commonly used antibiotics, highlighting the need for rational antibiotic use to prevent further resistance. Moreover, there is a need to conduct more regular multicenter studies to assess etiology, resistance, and susceptibility patterns of pneumonia-causing pathogens in Saudi Arabia.

Dietary nitrate supplementation, which improves skeletal muscle oxygen utilisation, vascular endothelial function and exercise capacity in people with chronic obstructive pulmonary disease, may benefit other lung conditions. In a double-blind, placebo-controlled, crossover study, in 19 adults with Group 3 pulmonary hypertension who desaturated during exercise, 140 mL of nitrate-rich beetroot juice improved endurance shuttle walk time compared with nitrate-depleted beetroot juice placebo (median (IQR) ESWT NR-BRJ 197 (140–273) s vs PL-BRJ 174 (107–229) s; median difference (MD) (95% CI) 30 (6.19 to 91.07) s, p=0.0281), endothelial function, flow-mediated dilatation (+3.40±5.47% vs −1.33±4.78; MD (95% CI) 4.73 (1.44 to 8.02), p=0.007) and lowered mean arterial blood pressure (−3.9 (−7.4 to −0.4) mm Hg, p=0.028).

IntroductionOscillating positive expiratory pressure (OPEP) devices are intended to facilitate sputum clearance in chronic obstructive pulmonary disease (COPD), but there is uncertainty as to their place in treatment pathways. We aimed to review the existing literature to establish the evidence base for their use.MethodsA systematic search of records up to March 2020 was performed on PubMed, CINAHL, Medline (Ovid), Cochrane and Embase to retrieve clinical trials that evaluated the efficacy of OPEP devices in patients with COPD. Two independent reviewers retrieved the titles, abstracts and full texts, and completed the data extraction.ResultsFollowing full-text review of 77 articles, eight (six randomised control trials and 2 cross-over studies) were eligible for inclusion. Pooled analysis showed low-grade evidence that the use of OPEP devices was associated with decreased COPD symptoms and exacerbations (OR 0.37, 95% CI 0.19 to 0.72), and enhanced exercise capacity; 6 min walk distance (mean difference (95% CI), 49.8 m (14.2 m to 85.5 m); p=0.009]). However, studies were mostly short term with the majority having a high risk of bias. The average acceptance, completion and drop-out rates were 82%, 91% and 8%, respectively.ConclusionThe use of OPEP devices can have a positive impact in COPD, but confidence in effect sizes is low and there is a need for further, higher quality studies to examine their long-term efficacy in COPD as well as to identify specific patient phenotypes that are more likely to respond.PROSPERO registration numberCRD 42016041835.

Heterozygous pathogenic variants in SLC12A2 are reported in patients with nonsyndromic hearing loss. Recently, homozygous loss-of-function variants have been reported in two patients with syndromic intellectual disability, with or without hearing loss. However, the clinical and molecular spectrum of SLC12A2 disease has yet to be characterized and confirmed. Using whole-exome sequencing, we detected a homozygous splicing variant in four patients from two independent families with severe developmental delay, microcephaly, respiratory abnormalities, and subtle dysmorphic features, with or without congenital hearing loss. We also reviewed the reported cases with pathogenic variants associated with autosomal dominant and recessive forms of the SLC12A2 disease. About 50% of the cases have syndromic and nonsyndromic congenital hearing loss. All patients harboring the recessive forms of the disease presented with severe global developmental delay. Interestingly, all reported variants are located in the c-terminal domain, suggesting a critical role of this domain for the proper function of the encoded co-transporter protein. In conclusion, our study provides an additional confirmation of the autosomal recessive SLC12A2 disease.

Background Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias. Methods The study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay. Results Thirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels. Conclusion Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.

Transcobalamin II (TC II) deficiency is a rare autosomal recessive disorder that typically manifests in early infancy. Symptoms include failure to thrive, vomiting, weakness, and pancytopenia. If left undiagnosed and untreated, it can be life-threatening. TC II is crucial for transporting cobalamin (vitamin B12), which plays a vital role in homocysteine and methylmalonic acid metabolism. It serves as a cofactor in neurotransmitter synthesis and protein methylation processes. In this study, we reviewed the clinical presentation, treatment approaches, and long-term outcomes of four patients with confirmed TC II deficiency. All subjects were born to consanguineous parents and exhibited symptoms between birth and four months of age. All patients presented with hematological abnormalities, elevated methylmalonic acid (MMA), and increased total homocysteine (tHcy) levels. Whole Exome Sequencing (WES) confirmed TC II deficiency in all cases, revealing diverse mutation spectra, primarily frameshift mutations (leu320Valfs*51, and IIe330Hisfs*9). No clear genotype-phenotype correlations were observed. The majority of patients were treated with intramuscular hydroxocobalamin (OH-Cbl), resulting in clinical and biochemical improvements. This study underscores the importance of early detection and appropriate management of TC II deficiency to prevent permanent morbidity and potentially fatal outcomes. Regular monitoring of clinical and neurological status, as well as MMA and tHcy levels, is essential to ensure adequate therapy. Intramuscular treatment is the preferred route to prevent neurological deficits and optimal markers normalization.

Objective: The aim of this systematic review was to summarize the literature regarding the clinical performance of zirconia crowns for primary teeth. Materials and Methods: Four electronic databases, Ovid, PubMed, Scopus, and Web of Science were searched. Clinical, observational, and laboratory studies were included. Studies that assessed the performance of zirconia crowns for primary teeth using outcomes such as gingival and periodontal health, parental satisfaction, color stability, crown retention, contour, fracture resistance, marginal integrity, surface roughness, and recurrent caries were included. Risk of bias was assessed using different assessment tools depending on the type of the assessed study. Results: Out of the 2400 retrieved records, 73 full-text records were assessed for eligibility. Thirty-six studies were included for qualitative analysis. The included studies reported that zirconia crowns for primary teeth were associated with better gingival and periodontal health, good retention, high fracture resistance, color stability, high parental acceptance, good marginal adaptation, smooth cosmetic surface, and no recurrent caries. Conclusion: Zirconia crowns are promising alternative to other restorative materials and crowns in the field of pediatric dentistry. They showed higher properties and performance in different clinical aspects and great parental satisfaction.

Background: Despite the advancements in chronic obstructive pulmonary disease (COPD) treatment, complications related to COPD exacerbation remain challenging. One associated factor is substance use/misuse among adults with COPD. Fewer studies, however, examined the prevalence and association between COPD and substance use and misuse. In addition, limited knowledge existed about the moderation effects of serious psychological distress and gender among adults with COPD and substance use/misuse. We aimed, therefore, to measure such prevalence, association, and moderation from nationally representative samples in the United States. Method: Data were drawn from the 2015–2019 National Survey on Drug Use and Health. Weighted logistic regressions were used to measure the associations of last-month tobacco (cigarettes, cigars, pipe, and smokeless tobacco products), other licit and illicit substance use (alcohol, marijuana, cocaine, crack, heroin, hallucinogens, and inhalants), and substance misuse (pain relievers, tranquilizers, stimulants, and sedatives) among adults with COPD. Serious psychological distress and gender were tested as moderators in the association between COPD and substance use/misuse. Results: The findings revealed that adults with COPD [Weighted N = 53,115,718) revealed greater odds of cigarettes [adjusted odds ratio (aOR) = 2.48 (95%CI = 1.80–3.42)) and smokeless tobacco (aOR = 3.65 (95%CI = 1.75–7.65)). However, they were less likely to use alcohol (aOR = 0.61 (95%CI = 0.45–0.84)). Adults with COPD who had serious psychological distress were more likely to use pipe tobacco and alcohol; however, they were less likely to use hallucinogens and inhalants. Finally, males compared to females with COPD were less likely to use smokeless tobacco. Conclusion: Adults with COPD in the United States were more likely to use tobacco products and less likely to use alcohol. In addition, serious psychological distress and gender were moderators in associations between COPD and substance use but not in substance misuse. Future studies should longitudinally assess the factors that may contribute to the initiation and progression of substance use and misuse among adults with COPD.