Efficacy and safety of front-line treatment regimens for Waldenstrom macroglobulinaemia: a systematic review and meta-analysis.

Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.

Dengue in Pregnancy: A Southeast Asian Perspective.

Dengue cases have been rising in recent years. In 2019 alone, over 658,301 of the 5.6 million reported cases originated from Southeast Asia (SEA). Research has also shown detrimental outcomes for pregnant infected women. Despite this, existing literature describing dengue's effects on pregnancy in SEA is insufficient. Through this narrative review, we sought to describe dengue's effects on pregnancy systemically and emphasize the existing gaps in the literature. We extensively searched various journals cited in PubMed and Ovid Medline, national clinical practice guidelines, and governmental reports. Dengue in pregnancy increases the risk of pre-eclampsia, Dengue Hemorrhagic Fever (DHF), fetal distress, preterm delivery, Caesarean delivery, and maternal mortality. Vertical transmission, intrauterine growth restriction, and stillbirth are possible sequelae of dengue in fetuses. We found that trimester-specific physiological impacts of dengue in pregnancy (to both mother and child) and investigations and management methods demanded further research, especially in the SEA region.

Efficacy and safety of different therapies of non-steroidal anti-inflammatory drugs against antibiotic monotherapy in the treatment of uncomplicated lower urinary tract infection: A systematic review.

This systematic review aimed to evaluate the efficacy of different non-steroidal anti-inflammatory drugs therapy (monotherapy or combined with antibiotics) against antibiotics monotherapy to understand the possible role of non-steroidal anti-inflammatory drugs in managing uncomplicated urinary tract infections and reduce overall antibiotic prescription. We searched four databases: PubMed, EMBASE, Scopus, and Cochrane CENTRAL. We included randomized controlled trials, which had included non-pregnant females above 18 years, published from 2010 to 2020 AD in the English language. We assessed risk of bias (ROB) using COCHRANE ROB version 2.0. We synthesized the conclusion from low ROB studies. Among five included studies, four studies compared non-steroidal anti-inflammatory drugs monotherapy against antibiotics monotherapy, and one study compared non-steroidal anti-inflammatory drugs + antibiotic therapy against antibiotic monotherapy. All studies with low ROB showed significantly higher events of symptom resolution by day 7 with antibiotic monotherapy compared to non-steroidal anti-inflammatory drugs monotherapy. Overall, adverse events were not significantly different in two of three low risk of bias studies; however, one study reported significantly higher adverse effects with non-steroidal anti-inflammatory drugs. Non-urinary tract infection-related adverse events were more common than urinary tract infections-related adverse events in both non-steroidal anti-inflammatory drugs and antibiotic groups. Urinary tract infection-related adverse events were higher in the non-steroidal anti-inflammatory drugs group compared to antibiotics. For every 20-60 participants treated, one would develop pyelonephritis additionally in non-steroidal anti-inflammatory drugs compared to antibiotics. Antibiotics were superior to non-steroidal anti-inflammatory drugs for treating uncomplicated lower urinary tract infections. However, further studies regarding the characteristics of patients likely to develop pyelonephritis on non-steroidal anti-inflammatory drugs monotherapy, and the effectiveness and safety of a combination of non-steroidal anti-inflammatory drugs and antibiotics therapy are essential to reduce the burden of antibiotics and their associated problems.

Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements.

Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center ( https://danio-code.zfin.org ) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.

Does technology-enhanced communication improve Helicobacter pylori eradication outcomes?-A meta-analysis.

BACKGROUND: Helicobacter pylori (H. pylori) is a highly prevalent organism that can induce an inflammatory state in the upper gastrointestinal tract and lead to complications such as peptic ulcer and gastric cancer. The treatment regime is complicated, and mild-to-moderate adverse effects are common, making patient compliance a key determinant of successful eradication. One attractive strategy is to leverage on technology-enhanced communication (TEC) strategies. However, the current data on the efficacy of TEC modalities in improving H. pylori eradication are limited. This is the first meta-analysis evaluating its effectiveness to the best of our knowledge. Thus, it is essential to evaluate the current body of evidence to learn the impact of TEC initiatives. METHODS: A literature search was done on PubMed, World of Science, and Embase. A total of 9 studies variably reported on compliance rate, eradication rate, adverse effect rate, symptom relief, patient satisfaction, treatment cost, patient disease awareness, and follow-up rates. RESULTS: This meta-analysis showed that TEC initiatives significantly improve patient compliance (OR 4.52, 95% CI 2.09 - 9.77, p < .01) and eradication rate (OR 1.98, 95% CI 1.34 - 2.93, p < .01) but not adverse effect rate (OR 0.65, 95% CI [0.27 - 1.57], p = .34). Due to the small number of studies and population sample, patient satisfaction, symptom relief, treatment costs, disease awareness, and follow-up rates were assessed qualitatively. CONCLUSION: TEC initiatives effectively improve compliance to the H. pylori eradication regime and increase the eradication rate.

Low incidence of venous thrombosis but high incidence of arterial thrombotic complications among critically ill COVID-19 patients in Singapore.

BACKGROUND: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. METHOD AND RESULTS: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). CONCLUSIONS: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

Robotic Versus Conventional Laparoscopic Surgery for Colorectal Cancer: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

BACKGROUND: Minimally invasive surgery has been considered as an alternative to open surgery by surgeons for colorectal cancer. However, the efficacy and safety profiles of robotic and conventional laparoscopic surgery for colorectal cancer remain unclear in the literature. The primary aim of this review was to determine whether robotic-assisted laparoscopic surgery (RAS) has better clinical outcomes for colorectal cancer patients than conventional laparoscopic surgery (CLS). METHODS: All randomized clinical trials (RCTs) and observational studies were systematically searched in the databases of CENTRAL, EMBASE and PubMed from their inception until January 2018. Case reports, case series and non-systematic reviews were excluded. RESULTS: Seventy-three studies (6 RCTs and 67 observational studies) were eligible (n = 169,236) for inclusion in the data synthesis. In comparison with the CLS arm, RAS cohort was associated with a significant reduction in the incidence of conversion to open surgery (ρ < 0.001, I2 = 65%; REM: OR 0.40; 95% CI 0.30,0.53), all-cause mortality (ρ < 0.001, I2 = 7%; FEM: OR 0.48; 95% CI 0.36,0.64) and wound infection (ρ < 0.001, I2 = 0%; FEM: OR 1.24; 95% CI 1.11,1.39). Patients who received RAS had a significantly shorter duration of hospitalization (ρ < 0.001, I2 = 94%; REM: MD - 0.77; 95% CI 1.12, - 0.41; day), time to oral diet (ρ < 0.001, I2 = 60%; REM: MD - 0.43; 95% CI - 0.64, - 0.21; day) and lesser intraoperative blood loss (ρ = 0.01, I2 = 88%; REM: MD - 18.05; 95% CI - 32.24, - 3.85; ml). However, RAS cohort was noted to require a significant longer duration of operative time (ρ < 0.001, I2 = 93%; REM: MD 38.19; 95% CI 28.78,47.60; min). CONCLUSIONS: This meta-analysis suggests that RAS provides better clinical outcomes for colorectal cancer patients as compared to the CLS at the expense of longer duration of operative time. However, the inconclusive trial sequential analysis and an overall low level of evidence in this review warrant future adequately powered RCTs to draw firm conclusion.

A Review on Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris (PRP) is an idiopathic, papulosquamous inflammatory dermatosis. It is characterized by hyperkeratotic follicular papules coalescing into orange-red scaly plaques, islands of sparing, and palmoplantar keratoderma. PRP can be subdivided into six clinical subtypes according to Griffiths' classification, based on age of onset, disease extent, prognosis, and other associated features. The sixth subtype of PRP occurs in individuals affected by HIV infection, and retroviral screening in all de novo cases of PRP is advised. Other reported associations include various infections, autoimmunity, drugs, and malignancies, although the true significance of these is still unclear. The genetic basis for familial cases, most commonly categorized under the fifth subtype, has been mapped to gain of function mutations in the caspase recruitment domain family, member 14 (CARD14) gene. Treatment of PRP remains a challenge to this day due to a paucity of high-quality evidence. Therapeutic regimens have been guided mostly by case reports and case series, with the mainstay of treatment being oral retinoids. Recently, biologics have emerged as a promising treatment for PRP. We present a review of the clinicopathologic features, pathogenesis, associated disorders, and treatment of PRP, with an emphasis and critical appraisal of the existing literature on the latter.

Depression and its psychosocial correlates among older Asian immigrants in North America: a critical review of two decades' research.

OBJECTIVE: This article critically reviews two decades of empirically based depression studies on older Asian immigrants (OAIs) in North America published in English. The Psychosocial Model of Late-Life Depression is proposed as the conceptual roadmap to help interpret the findings across studies. METHODS: Using multiple bibliographic databases, this review systematically summarized and evaluated findings in 24 studies in terms of: (a) the prevalence and severity of depression; (b) demographic, psychosocial, cultural, and health risk factors of depression; and (c) methodological approaches and designs. RESULTS: The results showed that depression is prevalent among OAIs and is linked to gender, recency of immigration, English proficiency, acculturation, service barriers, health status, relationship with children and family, and social support. However, considerable variability in the results, the sample sizes, and the use of measurements were also found across studies. DISCUSSION: Recommendations for future research and the provision of clinical and community services are discussed within the psychosocial model.