Higher supplemental oxygenation levels not better for COVID-19 patients experiencing hypoxia : JAMA

Higher supplemental oxygenation levels are not better for COVID-19 patients experiencing hypoxia suggests a new study published in the JAMA.

Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. A study was done to assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Multicenter randomized clinical trial included 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 European ICUs from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg.

Reference:

Nielsen FM, Klitgaard TL, Siegemund M, et al. Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial. JAMA. Published online March 19, 2024. doi:10.1001/jama.2024.2934

Keywords:

Higher, supplemental oxygenation levels, COVID-19 patients, experiencing hypoxia, JAMA, Nielsen FM, Klitgaard TL, Siegemund M

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Next-generation stool DNA test may improve sensitivity for colorectal cancer detection: NEJM

Colorectal cancer remains a leading cause of cancer-related mortality worldwide, highlighting the crucial need for effective screening strategies. A recent study unveiled the next-generation multitarget stool DNA test which is more effective in colorectal cancer screening. This innovative screening tool combines assessments of DNA molecular markers and hemoglobin levels to enhance specificity and accuracy in detecting colorectal cancer.

This research was conducted by Thomas Imperiale and colleagues on asymptomatic adults aged 40 and above who were undergoing screening colonoscopy and evaluated the performance of the new DNA test. The results revealed positive outcomes, with the test expressing a sensitivity of 93.9% for colorectal cancer and a specificity of 90.6% for advanced neoplasia, which includes colorectal cancer and advanced precancerous lesions.

Also, the next-generation DNA test demonstrated a sensitivity of 43.4% for advanced precancerous lesions by surpassing the performance of commercially available fecal immunochemical tests (FIT). While the FIT showed a sensitivity of 67.3% for colorectal cancer and 23.3% for advanced precancerous lesions, the new DNA test expressed superior performance in detecting both.

Despite the enhanced sensitivity, this next-generation DNA test showed a lower specificity for advanced neoplasia compared to FIT. However, no adverse events were reported during the study, underscoring the safety and feasibility of this innovative screening approach.

This study emphasized the significance of the outcomes in advancing colorectal cancer screening efforts. By highlighting the potential of next-generation DNA testing, there is improvement in early detection of colorectal cancer and precancerous lesions which ultimately saves lives through timely intervention.

Reference:

Imperiale, T. F., Porter, K., Zella, J., Gagrat, Z. D., Olson, M. C., Statz, S., Garces, J., Lavin, P. T., Aguilar, H., Brinberg, D., Berkelhammer, C., Kisiel, J. B., & Limburg, P. J. (2024). Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening. In New England Journal of Medicine (Vol. 390, Issue 11, pp. 984–993). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2310336

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Tirzepatide consistently reduces bodyweight regardless of BMI before treatment, shows new analysis

Tirzepatide, a medication authorised to treat obesity and/or type 2 diabetes, consistently reduces bodyweight regardless of the patient’s body mass index (BMI before treatment), from the range of overweight to class III obesity. The study, to be presented at this year’s European Congress on Obesity (Venice, Italy, 12-15 May) is by Prof Carel Le Roux, University College Dublin, Ireland, and Dr Louis J Aronne, Comprehensive Weight Control Center, Division of Endocrinology, Diabetes & Metabolism, Weill Cornell Medicine, New York, USA, and colleagues from Eli Lilly and Company, the manufacturer of tirzepatide.

Tirzepatide (Mounjaro®) was approved by the US Food and Drug administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound®) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro® label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.

This new analysis examined the impact of baseline body mass index (BMI) category on weight reduction in these trials. The phase 3 SURMOUNT trials examined the efficacy and safety of tirzepatide versus placebo in people with a BMI of 30 kg/m² and above or 27 kg/m² with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomisation) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomisation).

In this post-hoc subgroup analysis, BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m² and above (obesity class III). The authors examined the percent change in body weight from randomisation to week 72 (SURMOUNT-1, -2, and -3) or week 52 (SURMOUNT-4), as well as the proportions of participants achieving the weight reduction targets of 5, 10, and 15%. The analyses included all randomised participants who received 1 or more doses of the study drug (tirzepatide or placebo), excluding data after premature discontinuation of study drug.

The analysis showed that across SURMOUNT 1-4, tirzepatide treatment resulted in significant body weight reductions relative to placebo, irrespective of the BMI subgroup (see figure full abstract). In addition, more participants randomised to tirzepatide than placebo achieved the body weight reduction targets of 5, 10, and 15%. Across the BMI subgroups, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more vs. 30% with placebo in SURMOUNT-1, up to 93% vs. 43% in SURMOUNT-2, and up to 97% vs. 15% in SURMOUNT-3.

The respective proportions achieving body weight reduction of at least 10% were up to 93% vs. 16% in SURMOUNT-1, up to 76% vs. 14% in SURMOUNT-2, and up to 92% vs. 8% in SURMOUNT-3.

Furthermore, up to 85% of participants achieved weight reduction of at least 15% with tirzepatide vs. 7% with placebo in SURMOUNT-1, up to 60% vs. 3% in SURMOUNT-2, and up to 78% vs. 4% in SURMOUNT-3.

In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight reduction was 21%. After this lead-in period, further weight reductions of ≥5, ≥10, and ≥15% were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide vs. 2%, 2%, and 0% with placebo.

“Regardless of baseline BMI, tirzepatide consistently reduced body weight versus placebo in people with obesity across the SURMOUNT 1-4 trials. Further analyses are needed to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes. Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically-significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above).” said Dr. Aronne.

Prof Le Roux added: “Tirzepatide is one of the most effective treatments we have for the disease of obesity, and not only can we control the disease but we are also able to disrupt the complications of obesity such as type 2 diabetes.”

Reference:

New analysis shows tirzepatide consistently reduces bodyweight regardless of body mass index (BMI) before treatment, European Association for the Study of Obesity, Meeting: European Congress on Obesity (ECO2024).

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Multicomponent intervention may improve health-related quality of life among women with moderate to severe OAB: JAMA

Overactive bladder (OAB) is a common condition affecting women, often leading to decreased quality of life. While cognitive components are recognized in behavioral therapy for OAB, there’s a lack of studies evaluating the effectiveness of multicomponent interventions. A recent clinical trial conducted in Japan evaluated the effectiveness of a multicomponent intervention in improving health-related quality of life (HRQOL) for women with moderate to severe overactive bladder (OAB). The study found that participants who received the multicomponent intervention experienced significantly greater improvements in HRQOL compared to those in the waiting list control group.

This study was published in the journal JAMA Network Open by Satoshi F. and colleagues. clinical trial aimed to address this gap by examining the efficacy of a multicomponent intervention in improving health-related quality of life (HRQOL) for women with moderate to severe OAB.A multicenter, open-label, randomized clinical trial conducted in Japan recruited women aged 20 to 80 years with moderate to severe OAB. Participants were randomized to either four 30-minute weekly sessions of a multicomponent intervention or a waiting list control group. Primary outcomes included changes in HRQOL total scores, OAB symptom score, and frequency volume chart.

The key findings of the study were:

  • 79 women were randomized, with 39 participants in the intervention group and 40 in the waiting list control group.

  • Change in HRQOL total score from baseline to week 13 was significantly higher in the intervention group (23.9 points) compared to the waiting list group (11.3 points), with a significant difference of 12.6 points (P < .001).

  • Superiority of the intervention was confirmed for frequency of micturition and urgency but not for OAB symptom score.

The study demonstrates that a multicomponent intervention improves HRQOL for women with moderate to severe OAB, suggesting the cognitive component may be an effective treatment option. This highlights the importance of considering multicomponent approaches in managing OAB to enhance quality of life for affected individuals.

Reference:

Funada, S., Luo, Y., Uozumi, R., Watanabe, N., Goto, T., Negoro, H., Ueno, K., Ichioka, K., Segawa, T., Akechi, T., Ogawa, O., Akamatsu, S., Kobayashi, T., & Furukawa, T. A. Multicomponent intervention for overactive bladder in women: A randomized clinical trial. JAMA Network Open,2024;7(3):e241784. https://doi.org/10.1001/jamanetworkopen.2024.1784

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Sexual Dysfunction Common after Successful treatment of Ruptured Aneurysms: Study

A recent study published in Neurology India suggests that in cases of aneurysmal subarachnoid hemorrhage, sexual dysfunctions are common even after good clinical outcomes.

Sexual well-being is a fundamental requisite of happiness. The symptoms of sexual dysfunctions (SD) may be subtle or overt. The social stigma attached to this problem in conservative societies has kept this issue under the carpet for long times. Nevertheless, sexual dysfunction adversely affects interpersonal relationships and overall quality of life (QOL).

Male sexual arousal is a matter of central physiologic state with a linear sequence model of desire, arousal, orgasm, and resolution. It involves the process of relevant stimuli, general arousal, incentive motivation, and genital response. Literature suggests that patients with good neurologic recoveries after aneurysm clipping have a higher prevalence of sexual dysfunctions as compared to strokes of other etiologies. This disproportionate higher prevalence of sexual dysfunctions after aSAH may be due to the diffuse, global brain damage associated with SAH. Such an extensive injury is more likely to interfere with higher mental functions. It is mediated by dysfunction in bilaterally distributed, large-scale networks such as those underlying memory, executive function, and sexuality. SSASM evaluates both the physiological and subjective components of male sexual function.

A neglected factor is the location of the aneurysm and extent of SAH. Sexual function depends upon a complex network of peripheral and central pathways involving the autonomic and somatic nerves and the integration of numerous spinal and supra-spinal structures in the central nervous system. Hypothalamic and limbic regions play a pivotal role in this basic function. Brain is the master organ in sexual and positron emission tomography recordings during visual sexual stimulation showed activations in the orbitofrontal cortex, claustrum, anterior cingulate cortex, caudate, putamen, and hypothalamus. The anterior, mesial temporal lobe and basal forebrain structures are key regions for human sexual experience. These areas are intimately related to the Acom complex and the blood spillover from ruptured aneurysm in that region is likely to disrupt neurological functions, which include sexual activity as well.

Theoretically, these sexual dysfunctions may be caused by compression of the hypothalamic–pituitary complex by the aneurysm itself, post-hemorrhagic local tissue tamponade, toxic effects of the extravasated blood products, ischemia caused by vasospasm, raised intracranial pressure, hydrocephalus, or injury to delicate perforators of anterior circulation during surgery. This concept holds significant relevance for surgical procedures undertaken for Acom complex. The perforators arising from Acom supply hypothalamus and the hypothalamic-pituitary axis. Acom aneurysms are the most complex aneurysms of the anterior circulation due to flow dynamics and angioarchitecture of the Acom region. Anatomical structures in vicinity to Acom aneurysms are orbito-frontal cortex, claustrum, anterior cingulate cortex, caudate, putamen, and hypothalamus. The location of aneurysms and the perforators probably play a significant role in causing sexual dysfunctions with hypothalamus being final common pathway that controls sexual function. Sexual dysfunctions seem to be due to some neural abnormalities in these areas with Acom aneurysms having relatively more impact on hypothalamus as compared to aneurysms at other sites.

Researchers from PGI Chandigarh attempted to quantify this important parameter with comparative evaluation of anterior circulation aneurysms in different locations. As the sexual activity is related to hypothalamic pituitary axis and Papez circuit, they concentrated on the differential outcomes in different anterior circulation aneurysms only.

The authors prospectively included 40 male patients of ruptured intracranial aneurysms of anterior circulation (age range: 20–60 years; sexually active preoperatively), managed with craniotomy and clipping. They evaluated the sexual outcome in patients with excellent Glasgow outcome score (GOS) five at a minimum one year of follow-up. Patients with GOS-5 status at follow-up were broadly classified into two groups: Anterior communicating artery aneurysm (Acom), and non-Acom) aneurysms. We valued sexual outcome with Subjective Sexual Arousal Scale for Men  (SSASM) at follow-up, and compared in the two groups.

They found that grossly, 65% (26 of 40) patients of ruptured aneurysms scored below 135, suggesting some form of sexual dysfunctions. Statistically significant worse, mean SSASM score (114.520.44) for Acom aneurysm patients as compared to other aneurysms (129.517.90) highlights the increased sensitivity of midline neural structures to toxic blood products and damage.

The authors observed that spontaneous SAH adversely affects the interpersonal relationships and intimate sexual behavior, especially because of the loss of libido. In a patient with good outcome on traditional scales, maintaining the role of a partner and hence a family gradually becomes important. Only a limited number of patients (not more than 20%) are actually able to maintain the same employment and interpersonal relationships despite having a good scoring on the GOS. One of the limitations in these parameters is it takes into account sexual assessment only of the patient, not his partner. Any sexual activity demands a partner and the future assessments should also incorporate the viewpoint of the partner as the patient himself might be biased about his emotions and performance.

In SSASM analysis, mental satisfaction domain was especially low. It highlighted another point that good outcome aSAH patients with chronic complaints (post aSAH syndrome) typically lacked a structural brain damage correlate. Sexual dysfunction could be part of emotional problems, which many good outcome patients struggle with, including depression. 

This study revealed that sexual performance domain, mental satisfaction domain, and sexual assertiveness domain are more commonly and severely affected in patients who underwent surgery for Acom aneurysm as compared to aneurysm located in other regions of anterior circulation. Sexual health, as a significant outcome measure may be better detailed in cases undergoing aneurysm clipping and guarded outcome should become a part of preoperative counseling for aneurysms around Acom complex. Sexual rehabilitation is an important aspect among survivors of aSAH and needs the requisite evaluation of the partner, conclude the authors

Reference:

Tripathi, Manjul; Wankhade, Lomesh; Mohindra, Sandeep; Kumar, Santosh; Chauhan, Rajeev.

Sexual Dysfunction after Clipping of Ruptured Intracranial Aneurysms. Neurology India 72(1):p 110-116, Jan–Feb 2024.

 DOI: 10.4103/neuroindia.NI_1917_20

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Loss of tooth structure, vertical root fracture and periodontal disease tied to extraction of root canal-treated teeth: Study

Loss of tooth structure, vertical root fracture and periodontal disease tied to extraction of root canal-treated teeth suggests a new study published in the Journal of Endodontics.

This study investigated endodontically treated teeth that were replaced by dental implants at the University of North Carolina (UNC) at Chapel Hill School of Dentistry. The primary objective of this study was to determine the reasons leading to the extraction of endodontically treated teeth and their subsequent replacement with dental implants. The secondary objective was to evaluate the proportion of these teeth that, according to experienced endodontists, could have been preserved. The UNC-Chapel Hill’s dental electronic health records between 2004 and 2019 were probed for implant placement that replaced root canal-treated teeth. Preextraction radiographs and clinical charts were examined to ascertain the primary reason related to the extraction and to compile a profile for each case. In cases in which endodontic failure was the primary reason for extraction, radiographs and clinical findings were evaluated by 2experienced endodontists to assess potential treatment options. Results: Between 2004 and 2019, 29.3% (1564 of 5229) of teeth replaced by dental implants at UNC School of Dentistry had undergone root canal treatment, with the mandibular first molar being the most commonly replaced tooth. The leading reasons for extraction were recurrent caries associated with defective restoration (26.6%), fracture of coronal structure (21.5%), vertical root fracture (20.9%), compromised periodontal condition (13.8%), and endodontic failure (2.4%). Two experienced endodontists evaluated extractions due to endodontic failure and concluded that 61.7% of them could have been candidates for endodontic retreatment. Substantial loss of tooth structure was the leading cause of extraction of root canal-treated teeth, followed by vertical root fracture and periodontal disease. Although endodontic failure constituted a minor portion of the reasons for extraction, a considerable number of teeth were extracted due to vertical root fractures following root canal treatment. A significant proportion of the extracted teeth due to endodontic failure could have been considered as potential candidates for endodontic retreatment.

Reference:

Kim DH, Tawil PZ, Albouy JP, Duqum I. Retrospective Assessment of Endodontically Treated Teeth Replaced by Dental Implants. J Endod. 2024 Mar;50(3):310-315. doi: 10.1016/j.joen.2023.12.002. Epub 2023 Dec 21. PMID: 38141831.

Keywords:

Loss of tooth structure, vertical root fracture, periodontal disease,

Extraction, root canal-treated teeth, Study, Kim DH, Tawil PZ, Albouy JP, Duqum, Dental implants; endodontic microsurgery; endodontically treated teeth; ferrule; tooth fracture; tooth replacement.

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Healthy diet may reduce pace of aging and reduce dementia risk, suggests study

A healthier diet is associated with a reduced dementia risk and slower pace of aging, according to a new study at Columbia University Mailman School of Public Health and The Robert Butler Columbia Aging Center. The findings show that a diet-dementia association was at least partially facilitated by multi-system processes of aging. While literature had suggested that people who followed a healthy diet experienced a slowdown in the processes of biological aging and were less likely to develop dementia, until now the biological mechanism of this protection was not well understood. The findings are published in the Annals of Neurology.

“Much attention to nutrition in dementia research focuses on the way specific nutrients affect the brain” said Daniel Belsky, PhD, associate professor of Epidemiology at Columbia School of Public Health and the Columbia Aging Center, and a senior author of the study. “We tested the hypothesis that healthy diet protects against dementia by slowing down the body’s overall pace of biological aging.”

The researchers used data from the second generation of the Framingham Heart Study, the Offspring Cohort. Originating in 1971, participants in the latter were 60 years of age or older, were free of dementia, and also had available dietary, epigenetic, and follow-up data. The Offspring Cohort were followed-up at nine examinations, approximately every 4 to 7 years. At each follow-up visit, data collection included a physical examination, lifestyle-related questionnaires, blood sampling, and, starting in 1991, neurocognitive testing.

Of 1,644 participants included in the analyses, 140 of the participants developed dementia. To measure the pace of aging, the researchers used an epigenetic clock called DunedinPACE developed by Belsky and colleagues at Duke University and the University of Otago. The clock measures how fast a person’s body is deteriorating as they grow older, “like a speedometer for the biological processes of aging”, explained Belsky.

“We have some strong evidence that a healthy diet can protect against dementia,” said Yian Gu, PhD, associate professor of Neurological Sciences at Columbia University Irving Medical Center and the other senior author of the study, “But the mechanism of this protection is not well understood.” Past research linked both diet and dementia risk to an accelerated pace of biological aging.

“Testing the hypothesis that multi-system biological aging is a mechanism of underlying diet-dementia associations was the logical next step,” explained Belsky. The research determined that higher adherence to the Mediterranean-Dash Intervention for Neurodegenerative Delay diet (MIND) slowed the pace of aging as measured by DunedinPACE and reduced risks for dementia and mortality. Furthermore, slower DunedinPACE accounted for 27 percent of the diet-dementia association and 57 percent of the diet-mortality association.

“Our findings suggest that slower pace of aging mediates part of the relationship of healthy diet with reduced dementia risk, and therefore, monitoring pace of aging may inform dementia prevention,” said first author Aline Thomas, PhD, a Postdoc at the Columbia Department of Neurology and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain. “However, a portion of the diet-dementia association remains unexplained, therefore we believe that continued investigation of brain-specific mechanisms in well-designed mediation studies is warranted.”

“We suggest that additional observational studies be conducted to investigate direct associations of nutrients with brain aging, and if our observations are also confirmed in more diverse populations, monitoring biological aging, may indeed, inform dementia prevention,” noted Belsky. 

Reference:

Aline Thomas PhD, Calen P. Ryan PhD, Avshalom Caspi PhD, Zhonghua Liu PhD, Terrie E. Moffitt PhD, Karen Sugden PhD, Jiayi Zhou MPH, Daniel W. Belsky, Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study, Annals of Neurology, https://doi.org/10.1002/ana.26900. 

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SSRIs use at delivery may increase risk of postpartum hemorrhage in dose dependent manner: Study

Depression during pregnancy poses significant risks to both maternal and fetal health, including an increased risk of suicide and adverse newborn outcomes. While selective serotonin re-uptake inhibitors (SSRIs) are effective in treating depression, their use during pregnancy has been associated with bleeding complications at delivery. A recent study investigated the relationship between SSRIs and bleeding complications during delivery among pregnant women.

This study was published in the European Journal of Obstetrics Gynecology and Reproductive Biology by Malin O. and colleagues. A hospital-based cohort study was conducted at Karolinska University Hospital in Stockholm over a 5-year period from 2007 to 2011. The study included 334 women who delivered vaginally and were exposed to SSRIs at delivery, along with a control group of 31,929 women who delivered vaginally without SSRI exposure.

The SSRI-exposed group was further categorized into moderate (n = 246) or high (n = 88) SSRI dose at delivery. Electronic maternal health records were analyzed to assess bleeding complications at delivery in relation to SSRI dose. The key findings of the study were:

  • The study revealed a dose-dependent increase in the rate of postpartum haemorrhage (≥1000 ml) among women exposed to SSRIs, with rates of 8.4%, 14.6%, and 23.9% in the control group, moderate-dose group, and high-dose group, respectively (p ≤ 0.001).

  • There was a dose-dependent increase in the rate of postpartum anaemia, affecting 7.0%, 9.3%, and 15.9% of women in the respective groups (p = 0.001).

  • Mean blood loss also showed a dose-dependent pattern, with values of 406 ml, 483 ml, and 482 ml in the control group, moderate-dose group, and high-dose group, respectively (p ≤ 0.001).

  • Women exposed to SSRIs delivered earlier but did not have a higher prevalence of pre-eclampsia compared to the control group.

The findings of this study underscore the importance of carefully weighing the risks and benefits of SSRI use during pregnancy, particularly concerning bleeding complications at delivery. Clinicians should consider the dose dependency of SSRIs when managing depression in pregnant women, implementing individualized treatment plans to minimize adverse maternal and neonatal outcomes. Further research is warranted to elucidate the underlying mechanisms and optimize strategies for mitigating these risks while ensuring effective management of maternal mental health during pregnancy.

Reference:

Öndemark, M., Nordström, L., & Lindqvist, P. G. Dose-dependent increase in risk of bleeding and bleeding complications in relation to SSRI use at delivery. European Journal of Obstetrics, Gynecology, and Reproductive Biology,2024;296:265–269. https://doi.org/10.1016/j.ejogrb.2024.02.051

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Pneumococcal Conjugate Vaccines Shows Potential in Reducing Viral Respiratory Tract Infections: Study

Pneumococcal disease poses a significant health burden worldwide, and PCVs have been instrumental in reducing its incidence. Emerging evidence suggests that PCVs may also have indirect effects on viral RTIs by modulating pneumococcal-viral interactions.

Recent studies suggest that pneumococcal conjugate vaccines (PCVs) may not only prevent pneumococcal disease but also have an impact on viral respiratory tract infections (RTIs) through pneumococcal-viral interactions. To evaluate the broader effects of PCVs, a systematic review of interventional and observational studies from 2000 to 2022 was conducted. This study was published in The Journal Of Infectious Diseases by Ingrid T. and colleagues.

The systematic review analyzed 16 studies from 2000 to 2022, focusing on the vaccine efficacy/adjusted effectiveness (VE) and overall impact of PCV7, PCV9, PCV10, or PCV13 against viral RTIs. Studies included both interventional and observational designs, with a particular emphasis on pediatric populations.

Key Findings:

  • PCVs showed varying degrees of efficacy against viral RTIs in children, particularly against influenza, with VE ranging from 41% to 86%.

  • A randomized controlled trial demonstrated the efficacy of PCV9 against various viral RTIs, including human seasonal coronavirus, parainfluenza, and human metapneumovirus.

  • Limited data on PCV effectiveness in adults showed consistency with pediatric findings, although evidence was sparse.

  • PCV13 exhibited VE ranging from 4% to 25% against viral lower RTIs, 32% to 35% against COVID-19 outcomes, and 24% to 51% against human seasonal coronavirus.

  • No significant protection was observed against adenovirus or rhinovirus in either children or adults.

PCVs demonstrated efficacy against select viral RTIs, with the most robust evidence seen in influenza prevention among children. While limited, data in adults align with pediatric findings, suggesting a potential broader impact of PCVs beyond pneumococcal disease. This highlights the importance of considering the full spectrum of PCV effects in public health evaluations.

Reference:

Sepúlveda-Pachón, I. T., Dunne, E. M., Hanquet, G., Baay, M., Menon, S., Jodar, L., Gessner, B. D., & Theilacker, C. Effect of pneumococcal conjugate vaccines on viral respiratory infections: a systematic literature review. The Journal of Infectious Diseases,2024, https://doi.org/10.1093/infdis/jiae125

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Pooled saliva testing efficient, cost-sparing approach to identify newborns with asymptomatic CMV: Study

Israel: A recent study published in Nature Medicine demonstrates the benefits and wide feasibility of pooled saliva testing as a cost-sparing, efficient, and sensitive approach for universal screening of congenital cytomegalovirus (cCMV) infection.

The study emphasizes the significance of early detection through this method, especially for asymptomatic cases, highlighting its potential to revolutionize cCMV screening worldwide and improve long-term outcomes for affected infants by enabling timely interventions.

In a recent study, Professors Dana G. Wolf from Hadassah Hebrew University Medical Center and the Lautenberg Center for General and Tumor Immunology, and Moran Yassour from the Hebrew University, along with their teams and the Hadassah Neonatology team headed by Professor Smadar Eventov-Friedman, have successfully introduced pooled saliva polymerase chain reaction (PCR) tests for the universal screening of congenital cytomegalovirus (cCMV) infection. This new method helps detect and intervene early in the most common congenital infection, known for causing hearing loss and developmental problems.

Each year, tens of thousands of newborns are affected by cCMV infection, making it a leading cause of childhood neurologic deficits with lifelong implications. The global burden of cCMV is significant, and the absence of a universal screening method has posed challenges in promptly identifying and addressing cases. Current screening methods focus on high-risk cases, but this misses many asymptomatic infants. With a birth prevalence of 3.4 per 1,000 in the studied population, the successful implementation of pooled saliva tests, as demonstrated by the study, signifies a crucial advancement in early detection. The challenge lies in developing a reliable and efficient testing strategy due to the absence of a high-throughput screening test that can identify all infected neonates. This breakthrough has the potential to transform the lives of numerous infants annually, offering a more efficient and accessible means of identifying cCMV cases, particularly those that may present asymptomatically at birth and would otherwise go unnoticed.

The study, conducted in the two Hadassah Medical Center hospitals in Jerusalem from April 2022 through April 2023, involved the screening of 15,805 infants, constituting an impressive 93.6% of all live newborns. The implementation of pooled saliva tests emerged as a routine screening method during this 13-month period, showcasing its efficacy and reliability.

Researchers explored a sample pooling approach for congenital cytomegalovirus (cCMV) detection, where a group of samples is tested together. If the pooled sample is negative, all individual samples are considered negative; if positive, they are re-tested individually. The study aimed to leverage the low birth prevalence of cCMV (average 6.4 per 1000) for efficient screening. They predicted a 99.5% sensitivity for an 8-sample pool based on viral loads. Over 15,000 infants were screened using this method, achieving an empirical efficiency of 6, reducing required tests by 83%, with minimal sensitivity loss. cCMV was identified in 54 neonates, of whom more than half were asymptomatic at birth and would have been otherwise missed.

“Congenital cytomegalovirus (cCMV) is the most common intrauterine infection. We were driven by the unmet clinical need to identify all infants with cCMV, including those who are asymptomatic at birth, so that early treatment and monitoring could be delivered to a large proportion of infants who are otherwise not diagnosed.” Commented Professor Wolf. “This project was facilitated by the newly available pooled diagnostic approach and the interdisciplinary collaborations which we had established during the COVID-19 pandemic, which made universal screening of cCMV possible. Our findings project on the wide feasibility and benefits of saliva sample pooling to enhance universal neonatal screening for cCMV. Data derived from the implemented universal screening will serve to define the true burden of cCMV and assess future vaccines”

The study supports the use of pooled-saliva testing as a cost-effective and sensitive method for universal screening of congenital cytomegalovirus (cCMV). The pooling setup is easily integrable into medical laboratories, and parental acceptance was high. The research emphasizes the clinical importance of universal screening for early diagnosis, monitoring, and potential treatment of cCMV. While limited to two hospitals, the study suggests that universal screening is crucial to uncover undiagnosed cases, though prevalence estimates may vary across populations. Large-scale implementation needs consideration of potential case misses. Data from universal screening will help define cCMV burden, risk factors, and outcomes, emphasizing the need for further assessment in different subpopulations due to varying prevalence by race, ethnicity, and maternal seroprevalence.

Professor Moran Yassour commented, “This collaboration, born during the COVID-19 pandemic, has seamlessly extended its impact to address new medical challenges. Our transformative pooled-testing approach shifts from testing around 10% of newborns to universal testing of approximately 95%. While adjusting facility infrastructure may pose challenges, it’s a worthwhile, one-time investment with immense benefits for all newborns and their families worldwide.”

The successful implementation of pooled saliva tests represents a significant stride in the field of universal newborn screening for cCMV, offering a promising avenue for early detection and intervention. The research team anticipates that this approach will pave the way for enhanced global efforts in combating the impact of cCMV on newborns.

Reference:

Merav, L., Ofek Shlomai, N., Oiknine-Djian, E. et al. Implementation of pooled saliva tests for universal screening of cCMV infection. Nat Med (2024). https://doi.org/10.1038/s41591-024-02873-3.

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