Daily Archives: May 25, 2024
Randomized Clinical Trial: Dequalinium chloride demonstrates noninferiority to metronidazole in treating bacterial vaginosis – JAMA Netw Open
25 May, 2024 | 19:55h | UTCThis randomized clinical trial investigated the efficacy of dequalinium chloride compared to metronidazole for treating bacterial vaginosis in premenopausal women. Conducted across multiple centers from July 2021 to August 2022, the study involved 147 participants who were randomly assigned to receive either dequalinium chloride vaginal tablets or oral metronidazole. The primary outcome measured was the clinical cure rate shortly after treatment completion. Results showed that dequalinium chloride achieved a 92.8% cure rate, which was statistically noninferior to metronidazole’s 93.2% rate. Additionally, dequalinium chloride was better tolerated, with fewer adverse events reported compared to metronidazole. These findings suggest that dequalinium chloride is as effective as traditional antibiotic treatments for bacterial vaginosis and could be considered a viable non-antibiotic alternative due to its similar efficacy and enhanced tolerability.
Reference (link to free full-text):
Cohort Study: GLP1 receptor agonist use not associated with significant increase in thyroid cancer risk – The BMJ
25 May, 2024 | 19:51h | UTCA large Scandinavian cohort study investigated the association between glucagon-like peptide 1 (GLP1) receptor agonist use and thyroid cancer risk in Denmark, Norway, and Sweden from 2007 to 2021. The study compared 145,410 patients treated with GLP1 receptor agonists to 291,667 patients treated with dipeptidyl peptidase 4 (DPP4) inhibitors and included an additional analysis with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Results showed no significant increase in thyroid cancer risk among GLP1 users over a mean follow-up of 3.9 years, with a hazard ratio of 0.93 (95% CI, 0.66 to 1.31) compared to DPP4 inhibitor users. The study utilized nationwide cancer registers and employed an active-comparator, new user design to minimize confounding, using Cox regression models adjusted by propensity score weighting. The findings suggest that while small risk increases cannot be definitively ruled out, the use of GLP1 receptor agonists does not substantially elevate thyroid cancer risk.
Reference (link to free full-text):
Cohort Study: Prenatal opioid exposure linked to modest increase in neuropsychiatric disorders – The BMJ
25 May, 2024 | 19:50h | UTCThis nationwide birth cohort study from South Korea investigated the impact of prenatal opioid exposure on the risk of neuropsychiatric disorders among children. The study followed 3,128,571 infants born between 2010 and 2017 until the end of 2020. Researchers found that infants exposed to opioids prenatally showed a slightly increased risk of developing neuropsychiatric disorders, including mood disorders, attention deficit hyperactivity disorder, and intellectual disability. The increased risk was more pronounced with higher opioid doses, longer duration of use, and exposure during the first trimester of pregnancy. However, this association was not significant in sibling comparison cohorts, indicating a modest overall clinical impact. The study emphasizes the need for cautious interpretation due to its observational design and the specific conditions under which risk increases.
Reference (link to free full-text):
APA workgroup update maintains skepticism on pharmacogenomic tools for depression – Am J Psychiatry
25 May, 2024 | 19:47h | UTCA recent review by the American Psychiatric Association (APA) Council of Research Workgroup on Biomarkers and Novel Treatments revisits the use of pharmacogenomic (PGx) tools for selecting depression treatments. The review assesses new clinical trials and meta-analyses conducted from 2017 to 2022. Of the studies analyzed, few demonstrated significant efficacy in treatment response using PGx tools, with many suffering from methodological flaws such as lack of full blinding and insufficient control measures. Despite some trials showing promise, the overall evidence remains insufficient to support the widespread clinical application of PGx tools in managing major depressive disorder. The Workgroup reaffirms the 2018 conclusions and aligns with the U.S. Food and Drug Administration’s stance, recommending that future research should focus on more rigorous study designs and explore other potential benefits of pharmacogenomics, such as predicting rare adverse drug reactions.
Reference (link to abstract – $ for full-text)
Single-Arm Study: Evaluation of transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation – The Lancet
25 May, 2024 | 19:45h | UTCThis article discusses the ALIGN-AR study, a prospective, multicenter, single-arm trial conducted across 20 US sites. The study enrolled 180 high-risk patients suffering from moderate-to-severe or severe symptomatic aortic regurgitation, who were treated with the Trilogy transcatheter heart valve. The average age of participants was 75.5 years, with a roughly equal gender distribution among the 180 participants. The primary safety endpoint of the study was assessed against a prespecified performance goal of 40.5%, with results showing a 27% event rate, which was considered non-inferior (p<0.0001). Additionally, the primary efficacy endpoint, 1-year all-cause mortality, was 7.8%, significantly below the performance goal of 25%, also demonstrating non-inferiority (p<0.0001). The study reported a 95% technical success rate with adverse events such as new pacemaker implantation occurring in 24% of the patients. These findings suggest that the Trilogy transcatheter heart valve is a viable and effective option for high-risk patients, achieving favorable short-term clinical and hemodynamic outcomes. Further follow-up is necessary to determine long-term results and effects on left ventricular remodeling.
Reference (link to abstract – $ for full-text):
Post hoc analysis: Laparoscopic spleen-preserving hilar lymphadenectomy may improve 5-year survival in advanced proximal gastric cancer without greater curvature invasion – JAMA Surg
25 May, 2024 | 19:43h | UTCThis study presents the results of a post hoc secondary analysis from the Fuges-02 randomized clinical trial, investigating the effects of laparoscopic total gastrectomy (LTG) with and without spleen-preserving splenic hilar lymphadenectomy (LSPSHL) in 536 patients with resectable advanced proximal gastric cancer (APGC) lacking greater curvature invasion. Conducted from January 2015 to October 2018 with a minimum follow-up of five years, the study reported a significantly improved 5-year disease-free survival (DFS) rate of 63.9% in the LTG with LSPSHL group compared to 55.1% in the LTG alone group. The overall survival (OS) also favored the LSPSHL group at 66.2% versus 57.4% in the LTG group. Furthermore, the recurrence rate was lower in the LSPSHL group, with a notable reduction in recurrence at the No. 10 lymph node area, indicating a protective benefit from the addition of LSPSHL. The findings suggest a potential therapeutic advantage of incorporating LSPSHL in surgical protocols for APGC without greater curvature invasion, warranting further investigation through multicenter studies.
Reference (link to abstract – $ for full-text):
Phase 1-2 Study: Safety and efficacy of EDIT-101 CRISPR-Cas9 treatment for CEP290-associated retinal degeneration – N Engl J Med
25 May, 2024 | 19:42h | UTCThis study evaluates the safety and effectiveness of EDIT-101, a CRISPR-Cas9 gene-editing therapy, in treating inherited retinal degeneration caused by CEP290 IVS26 variants. Conducted as a phase 1-2, open-label, single-ascending-dose trial, it involved 14 participants (12 adults aged 17-63 and 2 children aged 9 and 14) who received subretinal injections of EDIT-101. Treatment doses varied, with two participants at a low dose, seven at an intermediate dose, and five at a high dose. The primary safety assessment showed no serious adverse events or dose-limiting toxic effects. Notably, 64% of participants exhibited significant improvements in visual acuity, retinal sensitivity to red light, or mobility. Additionally, improvements in vision-related quality of life were documented in six participants. These promising results suggest that EDIT-101 is safe and potentially effective, warranting further investigation into CRISPR-Cas9 gene therapy for similar genetic retinal conditions.
Commentary on X:
Original Article: Gene Editing for CEP290-Associated Retinal Degeneration (BRILLIANCE) https://t.co/LgSs2RGBZv #ARVO2024 @ARVOinfo pic.twitter.com/WztX2OvzXM
— NEJM (@NEJM) May 7, 2024
Reference (link to abstract – $ for full-text):
Cohort Study: Thick liquids not linked to better outcomes in hospitalized patients with dementia—further studies required – JAMA Intern Med
25 May, 2024 | 19:41h | UTC– This matched cohort study evaluated the impact of thick vs. thin liquids on clinical outcomes in 8916 hospitalized patients aged 65 and older with Alzheimer Disease and Related Dementias (ADRD) and oropharyngeal dysphagia. Conducted across 11 diverse hospitals in New York from January 2017 to September 2022, the study utilized propensity score matching to ensure comparability between the two diet groups based on demographic and clinical characteristics.
– The study found no significant difference in mortality rates between the thick and thin liquid groups (hazard ratio, 0.92; 95% CI, 0.75-1.14; P = .46). Patients on a thick liquid diet were less likely to require intubation (odds ratio [OR], 0.66; 95% CI, 0.54-0.80) but exhibited a higher incidence of respiratory complications such as pneumonia (OR, 1.73; 95% CI, 1.56-1.91).
– The findings suggest that while thick liquids may reduce the need for intubation, they may increase the risk of respiratory complications. These results underscore the necessity for future prospective studies to more definitively ascertain the effectiveness of thick liquids in improving clinical outcomes for this patient population.
Reference (link to abstract – $ for full-text):
Makhnevich, A. et al. (2024). Thick Liquids and Clinical Outcomes in Hospitalized Patients With Alzheimer Disease and Related Dementias and Dysphagia. JAMA Intern Med. Published online May 6, 2024. doi:10.1001/jamainternmed.2024.0736
Cohort Study: Efficacy of first-line color doppler ultrasound in diagnosing giant cell arteritis – Ann Intern Med
25 May, 2024 | 19:39h | UTCThis prospective multicenter study aimed to evaluate the efficacy of using color Doppler ultrasound of the temporal arteries as the first-line diagnostic tool for Giant Cell Arteritis (GCA) in 165 elderly patients with high clinical suspicion of the disease. The study followed participants over two years, comparing ultrasound results with temporal artery biopsy (TAB) and physician-based clinical diagnosis including other imaging tests. Key findings indicate that ultrasound confirmed GCA in 44% of cases, which was higher compared to TAB (17%) and clinical expertise (21%). The study showed that using ultrasound first can avoid the need for further invasive tests like TAB in patients with positive ultrasound results. The limitations of the study include its small sample size, unblinded test results, and the absence of a universally accepted objective diagnostic standard. However, it highlights the potential of ultrasound in the early and non-invasive diagnosis of GCA, potentially reducing the risk of severe complications by expediting treatment initiation.
Reference (link to abstract – $ for full-text):
Retrospective Analysis: 7% of outpatients in Massachusetts experience adverse events, predominantly drug-related – Ann Intern Med
25 May, 2024 | 19:37h | UTCThis retrospective study reviewed electronic health records from 11 outpatient sites in Massachusetts during 2018 to assess the incidence and nature of adverse events (AEs) in 3,103 patients. AEs were identified in 7.0% of the patients, translating to 8.6 events per 100 patients annually. Adverse drug events were the most frequent type of AE, constituting 63.8% of events, followed by healthcare-associated infections (14.8%) and surgical or procedural events (14.2%). The severity of these events was notable, with 17.4% being serious and 2.1% life-threatening, though none were fatal. Notably, 23.2% of these events were deemed preventable. The risk of experiencing at least one AE varied significantly by age and race, with higher rates observed among older adults and Black patients compared to other demographics. The study highlights the pressing need for targeted interventions to reduce AEs in outpatient settings.
Reference (link to abstract – $ for full-text):
RCT: Thrombectomy improves outcomes in acute stroke with large infarcts – N Engl J Med
25 May, 2024 | 19:35h | UTCStudy Design and Population: This randomized clinical trial investigated the efficacy of thrombectomy in combination with standard medical care versus medical care alone in patients with acute stroke and large infarcts. Participants included 333 patients with proximal cerebral vessel occlusion in the anterior circulation, presenting within 6.5 hours of symptom onset. They were randomized in a 1:1 ratio to either undergo thrombectomy or receive only medical care. An Alberta Stroke Program Early Computed Tomographic Score of ≤5 was used to define large infarcts.
Main Findings: The primary outcome, assessed by the modified Rankin scale score at 90 days, showed a median score of 4 in the thrombectomy group compared to 6 in the control group, indicating better functional outcomes with thrombectomy (generalized odds ratio, 1.63; 95% CI, 1.29 to 2.06; P<0.001). Mortality at 90 days was significantly lower in the thrombectomy group (36.1%) compared to the control group (55.5%) with an adjusted relative risk of 0.65. However, thrombectomy was associated with a higher rate of symptomatic intracerebral hemorrhage (9.6% vs. 5.7% in the control group).
Implications for Practice: The findings suggest that thrombectomy, when added to standard medical care, can significantly improve functional outcomes and reduce mortality in patients with large infarct strokes. However, the increased risk of symptomatic intracerebral hemorrhage must be considered when deciding on this intervention. These results support the broader use of thrombectomy in clinical settings with similar patient profiles but underscore the need for careful risk-benefit analysis due to the potential for serious hemorrhagic complications.
Reference (link to abstract – $ for full-text):
RCT: Ponatinib shows superior MRD-negative complete remission rates compared to Imatinib in newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia – JAMA
25 May, 2024 | 19:03h | UTCThis global phase 3 randomized clinical trial investigated the efficacy and safety of ponatinib versus imatinib in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). The study, conducted across 77 sites, enrolled 245 patients who were randomized in a 2:1 ratio to receive either ponatinib (30 mg/d) or imatinib (600 mg/d) alongside reduced-intensity chemotherapy. The primary endpoint of the trial was minimal residual disease–negative (MRD-negative) complete remission, assessed at the end of cycle 3. Results showed that ponatinib achieved a significantly higher MRD-negative complete remission rate of 34.4% compared to 16.7% with imatinib. Additionally, the safety profile between the two drugs was comparable, with arterial occlusive events being rare and similar across groups. These findings suggest ponatinib as a potentially preferable frontline therapy in this patient population due to its superior efficacy in achieving MRD-negative status without compromising safety.
Reference (link to abstract – $ for full-text):
RCT: Impact of single PSA screening invitation on 15-year prostate cancer mortality – JAMA
25 May, 2024 | 19:01h | UTCStudy Design and Population: This study is a secondary analysis of the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), which focused on the long-term effects of prostate-specific antigen (PSA) screening on prostate cancer mortality. It involved 415,357 men aged 50 to 69 years from 573 primary care practices across England and Wales. Participants were randomized to either receive a single invitation for a PSA screening or to a control group receiving standard practice without invitation. The follow-up period concluded on March 31, 2021, after a median duration of 15 years.
Main Findings: The intervention group, which received one PSA screening invitation, showed a prostate cancer mortality rate of 0.69% compared to 0.78% in the control group, translating to a rate ratio of 0.92 and demonstrating a statistically significant but modest reduction in death from prostate cancer. Additionally, the screening led to increased detection rates of low-grade and localized prostate cancer. However, there were no significant differences in detection of more advanced cancer stages between the two groups. All-cause mortality rates were similar across both groups.
Implications for Practice: While the introduction of a single PSA screening invitation was associated with a slight decrease in prostate cancer mortality over 15 years, the absolute reduction was small. These findings suggest that while PSA screening can detect cancer earlier, its impact on long-term survival is limited and should be weighed against the potential for overdiagnosis and overtreatment. Future strategies in prostate cancer screening might need to focus more on risk stratification and personalized screening approaches to maximize benefits and minimize unnecessary interventions.
Reference (link to abstract – $ for full-text):
RCT: Early minimally invasive surgery may improve outcomes in selected patients with intracerebral hemorrhage – N Engl J Med
25 May, 2024 | 18:58h | UTCStudy Design and Population: This multicenter randomized clinical trial investigated the efficacy of early minimally invasive surgical removal of intracerebral hemorrhage compared to medical management alone. The trial enrolled 300 patients within 24 hours of symptom onset, who had either lobar or anterior basal ganglia hemorrhages, with hematoma volumes ranging from 30 to 80 ml. An adaptation rule was applied partway through the trial, resulting in the exclusive enrollment of patients with lobar hemorrhages after 175 patients were initially enrolled.
Main Findings: Patients in the surgery group achieved a significantly higher mean score on the utility-weighted modified Rankin scale at 180 days (0.458) compared to the control group (0.374), with a difference of 0.084 and a posterior probability of superiority of 0.981. Notably, the benefit of surgery was pronounced among patients with lobar hemorrhages (mean difference 0.127), whereas no benefit was observed in patients with anterior basal ganglia hemorrhages. Additionally, the surgery group experienced a lower 30-day mortality rate (9.3%) compared to the control group (18.0%).
Implications for Practice: The results suggest that early minimally invasive surgery for intracerebral hemorrhage, particularly for lobar hemorrhages, offers significant functional benefits over medical management alone. These findings support the selective use of this surgical approach in clinical settings, potentially leading to improved patient outcomes. Further studies could explore the differential impact of hemorrhage location on surgical outcomes to refine treatment guidelines.
Reference (link to abstract – $ for full-text):
RCT: Omission of axillary dissection noninferior to complete dissection in clinically node-negative breast cancer with sentinel-node metastases – N Engl J Med
25 May, 2024 | 18:57h | UTCStudy Design and Population: This noninferiority trial explored the effects of omitting completion axillary-lymph-node dissection in patients with clinically node-negative primary T1 to T3 breast cancer who had one or two sentinel-node macrometastases. A total of 2766 patients were enrolled and randomized 1:1 to either undergo sentinel-node biopsy only or completion dissection. Patients received adjuvant treatment and radiation therapy as per national guidelines, focusing on recurrence-free survival as a secondary end point.
Main Findings: The study reported that the 5-year recurrence-free survival rates were 89.7% in the sentinel-node biopsy-only group and 88.7% in the dissection group, with a country-adjusted hazard ratio for recurrence or death at 0.89 (95% CI, 0.66 to 1.19), significantly below the noninferiority margin (P<0.001). This outcome demonstrates the noninferiority of the less invasive sentinel-node biopsy approach compared to the traditional dissection method in managing sentinel-node macrometastases.
Implications for Practice: The findings suggest that for clinically node-negative breast cancer patients with sentinel-node macrometastases, omitting axillary-lymph-node dissection could be considered a viable treatment option, potentially reducing the surgical burden without compromising recurrence-free survival outcomes. This could lead to adjustments in surgical practice and patient care strategies, emphasizing a less invasive approach while maintaining clinical efficacy.
Reference (link to abstract – $ for full-text):
Cohort Study: APOE4 Homozygosity as a Distinct Genetic Form of Alzheimer’s Disease with Early Biomarker Changes – Nat Med
25 May, 2024 | 18:55h | UTCThis cohort study investigated the impact of APOE4 homozygosity on Alzheimer’s disease (AD) by analyzing clinical, pathological, and biomarker data. The study utilized data from the National Alzheimer’s Coordinating Center and five additional large cohorts, comprising a total of 3,297 individuals for the pathological study and 10,039 for the clinical study. Results demonstrated that APOE4 homozygotes exhibited almost universal AD pathology and had significantly higher levels of AD biomarkers from age 55, compared to APOE3 homozygotes. By age 65, nearly all APOE4 homozygotes showed abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans, indicating a high biological penetrance of AD. These individuals also exhibited an earlier onset of symptoms, around age 65.1, and the progression and predictability of biomarker changes paralleled those observed in autosomal dominant AD and Down syndrome. However, in the dementia stage, amyloid and tau positron emission tomography scans showed no differences across haplotypes. The study concludes that APOE4 homozygosity represents a genetically distinct form of AD, underscoring the importance of tailored prevention strategies and treatments.
Reference (link to abstract – $ for full-text):
Cohort Study: First-trimester screening protocol achieves higher detection rates for preterm preeclampsia in nulliparous women – Hypertension
25 May, 2024 | 18:53h | UTCThis study aimed to evaluate the effectiveness of the Fetal Medicine Foundation’s (FMF) first-trimester screening protocol for predicting preterm preeclampsia in nulliparous women. A prospective multicenter cohort study was conducted involving 7554 nulliparous women, recruited at 11 to 14 weeks of pregnancy. Screening included assessing maternal characteristics, mean arterial blood pressure, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), and uterine artery pulsatility index. The risk assessment was performed by a third party, blinded to pregnancy outcomes, using receiver operating characteristic curves. Of the participants, 7325 remained eligible beyond 20 weeks of gestation. Among these, 65 (0.9%) developed preterm preeclampsia and 22 (0.3%) early-onset preeclampsia. The FMF screening test achieved a detection rate of 63.1% for preterm and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. In comparison, using criteria from the American College of Obstetricians and Gynecologists, the detection rates were 61.5% and 59.1%, respectively, but at a higher false-positive rate of 34.3%. The findings suggest that the FMF screening test is a more accurate and efficient method for predicting preterm preeclampsia in the first trimester among nulliparous women.
Reference (link to abstract – $ for full-text):
RCT: Laparoscopic hemihepatectomy for primary or metastatic cancer offers faster recovery and improved quality of life compared to open surgery – J Clin Oncol
25 May, 2024 | 18:52h | UTCStudy Design and Population: This study was a multicenter, randomized controlled, patient-blinded, superiority trial involving adult patients undergoing major liver resection (hemihepatectomy) primarily for cancer. Conducted across 16 European hospitals from November 2013 to December 2018, it included 352 patients who were randomized, with 332 completing the surgery—166 each in the laparoscopic and open surgery groups.
Main Findings: The primary outcome, time to functional recovery, was significantly shorter for the laparoscopic group, averaging 4 days compared to 5 days for the open surgery group (P < .001). Quality of life assessments showed higher scores for global health status and body image in the laparoscopic group. Although major complication rates were similar between the two groups, the laparoscopic approach demonstrated a notable advantage in the secondary cancer-specific outcome of time to adjuvant systemic therapy, which was significantly shorter compared to the open surgery group.
Implications for Practice: The findings suggest that laparoscopic hemihepatectomy not only enhances functional recovery and quality of life but also accelerates the initiation of adjuvant therapy in cancer patients without compromising safety or oncological outcomes. This evidence supports the broader adoption of laparoscopic techniques in major liver resections, particularly for cancer-related surgeries, to improve postoperative recovery and patient well-being.
Reference (link to abstract – $ for full-text):
Guidelines on the use of intravenous albumin in various clinical settings – CHEST
25 May, 2024 | 18:49h | UTCThe International Collaboration for Transfusion Medicine Guidelines provides comprehensive guidelines on the use of intravenous albumin across various clinical settings, including critical care, cardiovascular surgery, kidney replacement therapy, and complications of cirrhosis. The guideline emphasizes that there are few evidence-based indications supporting the routine use of albumin to improve patient outcomes. Key findings include:
1 – Critical Care: Limited recommendations for using albumin in adult, pediatric, and neonatal critical care, primarily advising against its routine use for volume replacement or managing hypoalbuminemia due to low or very low certainty of evidence.
2 – Cardiovascular Surgery: No recommendations for using albumin to prime cardiovascular bypass circuits or for volume replacement due to moderate to very low certainty of evidence.
3 – Kidney Replacement Therapy: Albumin is not suggested for preventing or managing intradialytic hypotension or improving ultrafiltration due to very low certainty of evidence.
4 – Cirrhosis Complications: Some conditional recommendations for using albumin in specific scenarios like large-volume paracentesis and spontaneous bacterial peritonitis due to low certainty of evidence; however, it is generally not suggested for other complications of cirrhosis.
Overall, the guidelines advise a cautious approach to albumin use, highlighting the need for more robust evidence to support its broader application in clinical practice.
Reference (link to free full-text):
Cohort Study: Impact of decreasing eGFR on serious adverse drug reactions in CKD patients – Am J Kidney Dis
25 May, 2024 | 18:48h | UTCThis prospective cohort study, part of the French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), involved 3,033 outpatients with moderate to advanced chronic kidney disease (CKD). The study aimed to explore the correlation between estimated glomerular filtration rate (eGFR) and the incidence of serious adverse drug reactions (ADRs). Over a median follow-up of 4.7 years, 360 patients experienced 488 serious ADRs, predominantly kidney and urinary disorders, and hemorrhages, constituting 70% of cases. The study identified antithrombotics and renin-angiotensin system inhibitors as the most common medication classes leading to these ADRs. A significant finding was that a decrease in eGFR is associated with a higher risk of serious ADRs, specifically acute kidney injury and bleeding, which were largely preventable or potentially preventable. The outcomes highlight the critical need for careful drug prescription and monitoring in CKD patients to mitigate serious ADRs.
Reference (link to free full-text):