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+ + + ++During the COVID-19 pandemic, many clinical sites shifted towards digital delivery of mental health services. However, there is still much to learn regarding tailoring interventions for trauma-affected populations, including military members, Veterans, and public safety personnel. This study examined perceptions of psychotherapies utilized for trauma-affected populations, as reported by Canadian military members, Veterans, and public safety personnel who completed such interventions and mental health clinicians who provided them. Specifically, we explored the shift to digital health use, what changed with this rapid shift, what needs, problems, and solutions arose, and important future considerations associated with delivering trauma-focused and adjunct treatments digitally. Quantitative survey data were collected from 11 Canadian patients (military members, Veterans, and public safety personnel with post-traumatic stress injury) and 12 Canadian mental health clinicians. Survey questions were adapted from the Alberta Quality Matrix for Health (AQMH) and Unified Theory of Acceptance and Use of Technology (UTAUT) model. As a follow-up, participants were invited to participate in either a semi-structured qualitative interview or focus group to further explore their perspectives on digitally delivered trauma-focused and adjunct therapies. Four clients and 19 clinician participants participated in an interview or focus group. In survey and interview/focus group results, patient and clinician participants reported that digitally delivered trauma and adjunct therapies offered similar treatment effectiveness as in-person delivery while also improving treatment access. Participants indicated unique advantages of digital delivery, including the increased accessibility of treatment, cost effectiveness, and more efficient use of resources. However, some participants struggled with using digital platforms and felt less comfortable working in a digital environment. Further research with a larger, more diverse population is required to corroborate our results and identify other avenues in which psychotherapies utilized for trauma-affected populations can be engaged with and improved upon. +
++Background The COVID-19 pandemic impacted diabetes mellitus clinical outcomes and chronic care globally. However, little is known about its impact in low-resource settings such as sub-Saharan Africa. Hence, to address this, we systematically conducted a scoping review to explore the COVID-19 impact on diabetes outcomes and care in countries of sub-Saharan Africa. Methods We applied our search strategy to PubMed, Web of Science, CINAHL, African Index Medicus, Google Scholar, Cochrane Library, Scopus, Science Direct, ERIC and Embase to obtain relevant articles published from January 2020 to March 2023. Two independent reviewers were involved in the screening of retrieved articles. Data from eligible articles were extracted from quantitative, qualitative and mixed methods studies. Numerical data were summarised using descriptive statistics, while a thematic framework was used to categorise and identify themes for qualitative data. Results We found 42 of the retrieved 360 articles eligible, mainly from South Africa, Ethiopia and Ghana (73.4%). COVID-19 increased the risk of death (OR 1.30,9.0, 95% CI), hospitalisation (OR 3.30,3.73: 95% CI), and severity (OR: 1.30,4.05, 95% CI) in persons with diabetes mellitus. COVID-19 also increased the risk of developing diabetes mellitus in hospitalised cases. The pandemic, on the other hand, was associated with disruptions in patient self-management routine and diabetes mellitus care service delivery. Three major themes emerged, namely, (i) patient-related health management challenges, (ii) diabetes mellitus care service delivery challenges, and (iii) reorganisation of diabetes mellitus care delivery. Conclusion COVID-19 increased mortality and morbidity among people living with diabetes mellitus. In addition, the COVID-19 pandemic worsened diabetes mellitus care management. Sub-Saharan African countries should, therefore, institute appropriate policy considerations for persons with diabetes mellitus during widespread emergencies. +
++Effective monitoring of infectious disease incidence remains a major challenge to public health. Difficulties in estimating the trends in disease incidence arise mainly from the time delay between case diagnosis and the reporting of cases to public health databases. However, predictive models usually assume that public data sets faithfully reflect the state of disease transmission. In this paper, we study the effect of delayed case reporting by comparing data reported by the Johns Hopkins Coronavirus Resource Center (CRC) with that of the raw clinical data collected from the San Antonio Metro Health District (SAMHD), San Antonio, Texas. An insight on the subtle effect that such reporting errors potentially have on predictive modeling is presented. We use an exponential distribution model for the regression analysis of the reporting delay. The proposed model for correcting reporting delays was applied to our recently developed SEYAR (Susceptible, Exposed, Symptomatic, Asymptomatic, Recovered) dynamical model for COVID-19 transmission dynamics. Employing data from SAMHD, we demonstrate that the forecasting ability of the SEYAR model is substantially improved when the rectified reporting obtained from our proposed model is utilized. The methods and findings demonstrated in this work have ample applicability in the forecasting of infectious disease outbreaks. Our findings suggest that failure to consider reporting delays in surveillance data can significantly alter forecasts. +
++Background/Objectives COVID-19 continues to pose a significant burden that impacts public health and the healthcare system as the SARS-CoV-2 virus continues to evolve. Regularly updated vaccines are anticipated to boost waning immunity and provide protection against circulating variants. This study evaluated vaccine effectiveness (VE) of mRNA-1273.815, a 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine, at preventing COVID-19-related hospitalizations and any medically attended COVID-19 in adults ≥18 years, overall, and by age and underlying medical conditions. Methods This retrospective cohort study used the Veradigm Network EHR linked to claims data to identify US adults ≥18 years of age who received the mRNA-1273.815 vaccine (exposed) matched 1:1 to individuals who did not receive a 2023-2024 updated COVID-19 vaccine (unexposed). Patients in the unexposed cohort were randomly matched to eligible mRNA-1273.815 recipients. Inverse probability of treatment weighting was used to adjust for differences between the two cohorts. The exposed cohort was vaccinated between September 12, 2023, and December 15, 2023, and individuals in both cohorts were followed up for COVID-19-related hospitalizations and medically attended COVID-19 until December 31, 2023. A Cox regression model was used to estimate the hazard ratio (HR). VE of the mRNA-1273.815 vaccine in preventing COVID-19-related hospitalizations and any medically attended COVID-19 was estimated as 100*(1-HR). Subgroup analyses were performed for adults ≥50, adults ≥65, and individuals with underlying medical conditions associated with severe COVID-19 outcomes. Results Overall, 859,335 matched pairs of mRNA-1273.815 recipients and unexposed adults were identified. The mean age was 63 years, and 80% of the study population was ≥50 years old. 61.5% of the mRNA-1273.815 cohort and 66.4% of the unexposed cohort had an underlying medical condition. Among the overall adult population (≥18 years), VE was 60.2% (53.4-66.0%) against COVID-19-related hospitalization and 33.1% (30.2%-35.9%) against medically attended COVID-19 over a median follow-up of 63 (IQR: 44-78) days. VE estimates by age and underlying medical conditions were similar. Conclusions These results demonstrate the significant protection provided by mRNA-1273.815 against COVID-19-related hospitalizations and any medically attended COVID-19 in adults 18 years and older, regardless of their vaccination history, and support CDC recommendations for vaccination with the 2023-2024 Omicron XBB.1.5-containing COVID-19 vaccine to prevent COVID-19-related outcomes, including hospitalizations. +
++Background: Phase IIb HIPRA-HH-2 study results showed that PHH-1V as first booster dose elicited a strong and sustained neutralising antibody response against various SARS-CoV-2 variants. Here, we report the safety and immunogenicity of a fourth booster dose of PHH-1V against the most prevalent Omicron SARS-CoV-2 variants in Spain. Methods: The HIPRA-HH-2 open-label extension study (NCT05142553) evaluated the safety and immunogenicity of PHH-1V as a fourth booster dose in subjects aged ≥18 years and followed for 6 months. Subjects received a fourth dose of PHH-1V 6-12 months after a previous regime of either two doses of BNT162b2 plus a third dose of PHH-1V (Cohort 1) or three doses of BNT162b2 (Cohort 2). Primary regulatory endpoint evaluated the neutralisation titres (GMT) against Omicron BA.1 on Day 14 of PHH-1V used as fourth dose in Cohort 2 vs the BNT162b2 used as third dose in initial HIPRA-HH-2 study. The immunogenicity of PHH-1V as fourth dose was also investigated by GMTs against Beta, Delta, and Omicron BA.1, BA.4/5 and XBB.1.5 on Days 14, 98 and 182 post-immunisation in the overall study population and in Cohorts 1 and 2 versus baseline. Safety of the fourth dose was also assessed. Findings: From September 2022, 288 subjects received PHH-1V as a fourth dose (Cohort 1 n=106; Cohort 2 n=182). A significant increase in neutralising antibodies against Omicron BA.1 subvariant at Day 14 was observed from the third homologous booster with mRNA vaccine compared to the fourth heterologous booster with PHH-1V (1739.02 vs 4049.01; GMT ratio 0.43 (95% CI: 0.28; 0.65; p-value < 0.0001). PHH-1V used as fourth booster induced a statistically significant increase in neutralising antibody titres 14 days after immunisation for all variants compared with baseline [GMFR on Day 14 (95%CI) was 6.96 (5.23, 9.25) for Beta variant; 6.27 (4.79, 8.22) for Delta variant; 9.21 (5.57, 15.21) for Omicron BA.1 variant; 11.80 (8.29, 16.80) for Omicron BA.4/5 variant and 5.22 (3.97, 6.87) for Omicron XBB.1.5 variant]. Titres remained significantly higher compared with baseline at 3 and 6 months post-vaccination. Cohort comparison revealed no significant differences at 14 , 98 and 182 days post-vaccination. The most frequent adverse events were injection site pain (Cohort 1: 84.0%; Cohort 2: 77.5%) and fatigue (Cohort 1: 17.9%; Cohort 2: 29.1%). No subjects experienced severe COVID-19 infection. Interpretation: The PHH-1V vaccine as a booster induced a potent and sustained neutralising antibody response against previous circulating Beta, Delta variants and Omicron BA.1, BA.4/5, and XBB.1.5 subvariants in subjects previously vaccinated with three doses regardless of previous regimen. These findings suggest that PHH-1V could be an appropriate strategy for upcoming heterologous vaccination campaigns. +
++Estimation of transmission and contact rate parameters among individuals in different age groups is a key point in the mathematical modeling of infectious disease transmission. Several approaches exist for this task but, given the complexity of the problem, the obtained values are always approximate estimations that hold in particular conditions. Our goal is to contribute to this task in the event of an emerging disease. We propose a methodology to estimate the contact rate parameters from the fraction of the incidence reported in each age group at the beginning of the epidemic spread. Working with an age-structured SIR model, we obtain an equation that relates the contact parameters to various epidemiological quantities that could be accessible through different sources. We apply the method to obtain information about the contact structure by age during the COVID-19 epidemic spread in Greater Buenos Aires (Argentina) in 2020. As we have the fractions of reported incidence by age but only rough estimations of other quantities involved in the method, we define several epidemiological scenarios based on various hypotheses. Using the different sets of contact parameters obtained, we evaluate control strategies and analyze the dependence of the results on our assumptions. The proposed method could be useful to obtain a fast first insight of a new emergent disease at the beginning of epidemic spread using the accessible information. +
++We mapped the 2020-2023 daily Covid-19 case data from the World Health Organization (WHO) to the original SIR model of Karmack and McKendrick for multiple pandemic recurrences due to the evolution of the virus to different variants in forty countries worldwide. The aim of the study was to determine how the SIR parameters are changing as the virus evolved into variants. Each peak in cases was analyzed separately for each country and the parameters: reff (pandemic R-parameter), Leff (average number of days an individual is infective) and alpha (the rate of infection for contacts between the set of susceptible persons and the set of infected persons) were computed. Each peak was mapped to circulating variants for each country and the SIR parameters (reff, Leff, alpha) were averaged over each variant using their values in peaks where 70% of the variant sequences identified belonged to a single variant. This analysis showed that on average, compared to the original Wuhan variant (alpha = 0.2), the parameter alpha has increased to alpha = 0.5 for the Omicron variants. The value of reff has decreased from around 3.8 to 2.0 and Leff has decreased from 15 days to 10 days. This is as would be expected of a virus that is coming to equilibrium by evolving to increase its infectivity while reducing the effects of infections on the host. +
++Introduction: COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin. Methods: This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. Results: 10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). Conclusions: Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders. +
++Individuals9 perceptions of disease influence their adherence to preventive measures, shaping the dynamics of disease spread. Despite extensive research on the interaction between disease spread, human behaviors, and interventions, few models have incorporated real-world behavioral data on disease perception, limiting their applicability. This study novelly integrates disease perception, represented by perceived severity, as a critical determinant of behavioral change into a data-driven compartmental model to assess its impact on disease spread. Using survey data, we explore scenarios involving a competition between a COVID-19 wave and a vaccination campaign, where individuals9 behaviors vary based on their perceived severity of the disease. Results demonstrate that behavioral heterogeneities influenced by perceived severity affect epidemic dynamics, with high heterogeneity yielding contrasting effects. Longer adherence to protective measures by groups with high perceived severity provides greater protection to vulnerable individuals, while premature relaxation of behaviors by low perceived severity groups facilitates virus spread. Epidemiological curves reveal that differences in behavior among groups can eliminate a second infection peak, resulting in a higher first peak and overall more severe outcomes. The specific modeling approach for how perceived severity modulates behavior parameters does not strongly impact the model9s outcomes. Sensitivity analyses confirm the robustness of our findings, emphasizing the consistent impact of behavioral heterogeneities across various scenarios. Our study underscores the importance of integrating risk perception into infectious disease transmission models and highlights the necessity of extensive data collection to enhance model accuracy and relevance. +
+Effects of Unsupervised Inspiratory Muscle Training on Ventilation Variability in Post-covid-19 Patients. - Conditions: COVID-19
Interventions: Device: Experimental Group
Sponsors: Universidade Federal do Rio Grande do Norte
Recruiting
A Phase IV Vaccine Study Under the National Cohort Study of Effectiveness and Safety of SARS-CoV-2 (COVID-19) Vaccines. - Conditions: SARS CoV 2 Infection
Interventions: Biological: Johnson & Johnson
Sponsors: Jens D Lundgren, MD; Ministry of the Interior and Health, Denmark
Completed
Detoxification From the Lipid Tract - Conditions: COVID-19 Vaccine Adverse Reaction
Interventions: Device: electroencephalogram biofeedback; Device: electrical brain stimulation; Device: ultra-low frequency transcranial magnetic stimulation; Drug: Sertraline Hydrochloride; Drug: Clonazepam; Drug: Alprazolam; Drug: Metoprolol; Drug: Olanzapine; Drug: Pravastatin Sodium 20 MG; Drug: Sacubitril Valsartan Sodium Hydrate
Sponsors: Pachankis, Yang I., M.D.; First Affiliated Hospital of Chongqing Medical University
Completed
Covid-19 and Influenza Oral Vaccine Study - Conditions: covid19 Infection; Influenza, Human
Interventions: Biological: Covid-19 vaccine; Biological: Influenza vaccine
Sponsors: Vaxine Pty Ltd; Australian Respiratory and Sleep Medicine Institute Ltd
Not yet recruiting
A Study of an Investigational mRNA-1273.815 COVID-19 Vaccine in Previously Vaccinated Adults - Conditions: SARS-CoV-2
Interventions: Biological: Investigational mRNA-1273.815; Biological: Licensed Spikevax Vaccine
Sponsors: ModernaTX, Inc.
Not yet recruiting
A Study of the Efficacy of Troxerutin in Preventing Thrombotic Events in COVID-19 Patients - Conditions: COVID 19 Associated Coagulopathy
Interventions: Drug: Troxerutin; Drug: Placebo; Drug: placebo + low molecular weight heparin; Drug: troxerutin + low molecular weight heparin
Sponsors: Westlake University; Shaoxing Central Hospital
Recruiting
The Use of Isatidis Root and Forsythia Oral Liquid for the Treatment of Mild Cases of COVID-19: A Trial Clinical Study - Conditions: Treatment of Mild Cases of COVID-19
Interventions: Drug: Langenlianqiao; Drug: LianhuaQingWen; Other: placebo control group
Sponsors: Central South University
Completed
Fascial Tissue Response To Manual Therapy: Implications In Long Covid Rehabilitation - Conditions: COVID-19
Interventions: Other: Guidebook; Other: Guidebook and Myofascial Reorganization® (RMF).
Sponsors: University of the State of Santa Catarina; Larissa Sinhorim
Recruiting
Effect of Probiotic Strain Lactobacillus Paracasei PS23 on Brain Fog in People With Long COVID - Conditions: Long COVID; Brain Fog; Cognitive Change
Interventions: Dietary Supplement: Lactobacillus paracasei PS23; Dietary Supplement: microcrystalline cellulose
Sponsors: Taipei Veterans General Hospital, Taiwan
Not yet recruiting
Evaluation of the Impact of Rehabilitation Strategies and Early Discharge After Respiratory Failure - Conditions: Acute Respiratory Failure
Interventions: Behavioral: Standard of Care; Behavioral: Rehabilitation
Sponsors: Hospital Israelita Albert Einstein
Not yet recruiting
Inside Israel’s Bombing Campaign in Gaza - The Israeli journalist Yuval Abraham on his investigations of the I.D.F.’s use of A.I.-backed targeting systems and the dire cost to Palestinian civilians. - link
Is This Israel’s Forever War? - Foreign-policy analysts whose careers were shaped by the war on terror see troubling parallels. - link
Jessica Tisch, the Ex-N.Y.P.D. Official Trying to Tame New York’s Trash - The city has lived in filth for decades. Can Jessica Tisch, a scion of one of the country’s richest families, finally clean up the streets? - link
Battling Under a Canopy of Russian and Ukrainian Drones - The commander of one of Ukraine’s most skilled units sent his men on a dangerous mission that required them to elude a swarm of aerial threats. - link
Maggie Rogers’s Journey from Viral Fame to Religious Studies - The singer-songwriter’s sudden celebrity made her a kind of minister without training. So she went and got some. - link
+Plus, how to think about building your legacy. +
++On the Money is a monthly advice column. If you want advice on spending, saving, or investing — or any of the complicated emotions that may come up as you prepare to make big financial decisions — you can submit your questions on this form. +
++Curious about what a financial expert would suggest about planning for the future. Seems like there is a lot of uncertainty — and as a millennial, lots of income difference within my generation. What happens if they raise the retirement age to 70? What if something else changes before millennials are able to retire? +
++I don’t know if you know much about Dale Carnegie, but in addition to writing the famous self-help book How to Win Friends and Influence People, he also wrote a slightly less popular book called How to Stop Worrying and Start Living. +
++There’s a reason why How to Win Friends and Influence People is the kind of book that everyone’s heard of and How to Stop Worrying and Start Living isn’t. Everyone wants to become an influencer, after all — and not everyone is ready to do the work required to stop worrying and start living. +
++One of the first tasks, as Carnegie explains, is to imagine the worst-case scenario in all its worst-cased-ness. +
++Then, Carnegie advises, ask yourself what you can do to either prevent or accept that worst-case scenario. +
++And then — and here’s why nobody reads this book anymore — you have to do it. +
++In your case, you’re worried about the federal government raising the retirement age to 70. This is not an unreasonable concern. I’m an “elder millennial,” so I was alive when the government raised the retirement age from 65 to 67, and it’s not much of a stretch to imagine a future in which we can only begin collecting full Social Security benefits after our 70th birthdays. +
++Can either of us prevent this scenario? Maybe, depending on how we choose to vote in the next few elections, but it’s unlikely we’ll have any direct impact. +
++This means that you have to accept the scenario as a possibility — and to stop worrying and start living, you have to plan for a future in which you do not receive full Social Security benefits until age 70. You may even want to plan for a future in which you are no longer allowed to collect partial benefits if you retire early. +
++Does that mean you need to put more money into savings and/or investments every month? Not necessarily. Depending on your current retirement plan, the compound interest associated with your accumulated assets could help you cover the three-year gap between 67 and 70. On the other hand, a bear market (that’s the bad one) could decimate the value of your portfolio no matter how much you save in the next three decades. +
++This is why I always advise people to focus on savings vehicles that provide guaranteed returns, such as CD ladders, as well as methods of building wealth that aren’t directly associated with investments. Getting promoted — or, in some cases, changing careers — could earn you much more money than you might get from a mutual fund. Moving to a lower cost-of-living area could also allow you to save more, as well as take advantage of opportunities like homeownership that might otherwise be more difficult. Living near family and/or living within a strong community can also provide the kind of support that can sustain you when times get tough. And if you live in the kind of area that allows you to participate in activities you love with people you care about, you might be less likely to spend money on distractions like impulse purchases, streaming media, and expensive vacations. This, in turn, could give you the financial and social resources to help other people who might need support, which is one way to address the income inequality issues that are prevalent across nearly all generations. +
++All of these changes take work, and some of them come with up-front costs — which is another reason why How to Stop Worrying and Start Living never really took off as a self-help text. Still, it’s an extremely good template to help you prepare for the uncertainty of the next 30 years. +
++Why save? I’m retired. You can’t take it with you … +
++No, you can’t. As long as you have enough set aside to cover your expenses for the rest of your estimated lifespan (factoring in inflation, naturally), as well as any money you may need for end-of-life care (which is more expensive than many people realize), you can spend the rest on personal indulgences if you want! +
++That said, I’d advise you to stop thinking about taking it with you and start thinking about how you can give back. Do you really want your life’s work to end up in the pockets of Amazon and Margaritaville? Isn’t there someone a little closer to home who might benefit from your legacy? +
++If you have family or a community of friends who have provided comfort, support, and connection throughout your life, for example, ask yourself whether you have the extra resources to provide support in return. Some people leave an inheritance; other people make financial gifts while they’re still alive. If you’d rather not use financial resources, consider giving your time. Driving a friend to a medical appointment, sitting with them as they meet their medical team, and taking notes on the recommended treatment plans is one of the best things you can do for someone you love. +
++If you don’t have a lot of close family or friends at the moment, consider supporting an organization or a local cause, and consider volunteering in order to start making a few more in-person connections. They’ll be worth more than you realize, especially as the decades continue to progress. +
++There’s one more factor to consider, and that’s whether you might be eligible for Medicaid in your later years. If you’re thinking about Medicaid as an option, perhaps after spending down the last of your savings, you may want to set up a meeting with a financial adviser to discuss how to ethically take advantage of this government aid program. Medicaid is designed to help lower-income households access medical care, and many older Americans use both Medicaid and Medicare (a federal health insurance program) to help them manage the expenses associated with advanced aging. +
++That said, accessing Medicaid could place a burden on your surviving family members. Many people don’t realize that Medicaid may be able to claim any remaining financial assets to cover the costs of providing end-of-life care, including real estate. The recent New York Times article “When Medicaid Comes After the Family Home” offers a good summary of what to expect, so read that carefully and include it in your long-term financial planning. It’s also worth remembering that the infamous Medicaid five-year “Look-Back Period” prevents people from gifting or donating their assets immediately prior to applying for benefits. Some people set up trusts to preserve their assets while remaining eligible for Medicaid, but this is the sort of issue that you’ll need to discuss with a professional. +
++All I can tell you, as an advice columnist, is to think carefully about where you want your money to go since you already know that you can’t take it with you — and to have conversations with family members and financial professionals to ensure that any remaining assets are distributed in a way that feels meaningful to you and the people you love. +
+For the last 100 years, we’ve only had one TB vaccine — and it leaves a lot to be desired. +
++It’s 2024, and people are still dying from … consumption. +
++This ancient disease, known today as tuberculosis or TB, has plagued humanity for thousands of years, and as recently as a few hundred years ago, was thought to be responsible for some 25 percent of all deaths in Europe and North America. +
++Today, TB is both preventable and treatable — there’s a century-old vaccine, effective antibiotics, and known behavioral and sanitation safeguards that disrupt transmission. Yet in 2022, more than 10 million people globally still fell ill from TB and 1.3 million died, making it the second deadliest infectious disease that year. (More people die from TB generally, but Covid-19 temporarily outpaced it.) More than 80 percent of those TB cases and deaths occur in low- and middle-income countries. +
++That’s largely because people in those countries are more likely to suffer from contributing risk factors to TB, such as malnourishment and HIV. +
++But beyond those factors, when it comes to preventing illness and death in these regions, physicians, researchers, and public health officials say that the available vaccine and treatments don’t do enough: The vaccine is given to infants and only offers protection in the first few years of life, leaving large swaths of people at risk, while antibiotic treatments take months to cure the disease. +
++“TB is a disease of poverty,” explained Helen McShane, professor of vaccinology at the University of Oxford, where she and her team are developing a new TB vaccine among other TB research. “There have been decades of neglect where there was no funding for new drugs or new vaccines for TB.” +
++But for the first time, promising new vaccines are now in the pipeline and may help prevent TB in adolescents and adults who currently have no such protection. These vaccines might also be more effective than what we have right now. Several are undergoing phase 3 trials — the last step before vaccine makers can apply to international and national agencies for approval. +
++“It is excellent news,” said Matteo Zignol, unit head of the WHO’s Global Tuberculosis Programme. The success of the first wave of vaccines has helped usher in more support and funding to the field, but many researchers say we will need more than just a few effective vaccines. “We all wish [the M72/AS01E vaccine trial] is going to be a successful trial, but in any case, this is going to be like a first generation sort of new vaccine, and we really need more candidates to be able to help the epidemic.” +
++It’ll likely still take years for the vaccines to be rolled out, but if approved, the new vaccines have the potential to save hundreds of thousands of lives, making an enormous dent in a disease that has killed humans for millennia. +
++One of the strange things about tuberculosis is that having the bacterium that causes TB doesn’t mean you have the disease. In a 2016 paper published in PLOS Medicine, researchers estimated that nearly 25 percent of the world’s population has a latent TB infection. For most people, though, the bacteria remain dormant and never go on to cause disease. +
++Basic preventative measures — such as improving sanitation, ensuring proper ventilation in hospitals and laboratories, and proactively identifying and treating high-risk patients — helped greatly reduce TB cases in developed countries like the US, where there were around 8,000 TB cases reported in 2022. Many lower-income countries, unfortunately, still have underdeveloped public health systems and lack the resources to implement the multipronged approach necessary to stamp out TB. That is where vaccination can be a critical tool. +
++The world’s first and only available TB vaccine, the Bacille Calmette-Guérin (BCG) vaccine, was created in 1921. Given the low burden of TB in the US, BCG is not routinely given to infants, but it is commonly used in many other countries. In Africa and Southeast Asia — the regions with the highest TB burden — 80 and 91 percent of 1-year-olds received the BCG vaccine in 2022, respectively, according to estimates by the WHO. +
++The BCG vaccine is considered safe with rare side effects, but it’s not very effective. One meta-analysis of 26 studies reported that when the BCG vaccine was given during infancy, it was 37 percent effective against all forms of TB during the first five years of life, but did not offer protection among adolescents and adults. +
++The way TB infects someone also plays a role in how contagious the disease can be and limits the vaccine’s ability to prevent disease. Usually, TB infects the lungs — that’s pulmonary TB. But Mycobacterium tuberculosis can infect the liver, bones, spinal cord, brain, urinary tract, bladder, kidneys, and even the intestines. When TB infects organs other than the lungs, it’s called extrapulmonary TB. Individuals with extrapulmonary disease don’t usually infect others, while those with TB in their lungs can more easily spread the bacterium to others by breathing, coughing, or sneezing. +
++Pulmonary infections account for the majority of TB morbidity and mortality. Exact percentages vary by country, but globally around 63 percent of all TB cases were pulmonary in 2021, according to the WHO. BCG vaccine efficacy against pulmonary TB infections still remains a bit of a mystery as studies have reported efficacy rates ranging from 0 to 80 percent and efficacy tends to be lowest in high-burden countries close to the equator. +
++Researchers are not quite sure why this is. One theory is that those who live closer to the equator are more likely to be exposed to non-tuberculous mycobacteria, which are similar to the pathogen that causes TB. This exposure confers preexisting immunity which may actually hinder the BCG vaccine from doing its job, McShane said. +
++All in all, researchers estimate that the BCG vaccine prevents only 5 percent of all vaccine-preventable deaths due to TB. For comparison, vaccines for measles, smallpox, and polio are 93, 95, and 90 percent effective in preventing disease, respectively. +
++Despite the limitations of the BCG vaccine, no new vaccine candidates have emerged in the past 100 years. M. tuberculosis is notoriously difficult to make a vaccine for because the bacterium has an adept ability to evade the human immune system. As Vox’s Dylan Matthews reported last year, “TB is a hard disease to vaccinate against. While most vaccines target viruses, TB is a bacterium, and one with a strange lifecycle.” +
++Economic and political factors play a role as well. After many high-income countries made huge strides in reducing TB in the late 1990s and early 2000s, they allocated few resources to further research and development of new vaccines and treatments, focusing instead on other health threats such as cancer and cardiovascular disease. TB fell into the category of neglected diseases. +
++McShane recalled when her team conducted the first trials of a new generation TB vaccine in 2002. “At the time, there were about 50 candidate vaccines being tested for malaria and about 50 for HIV,” she said. “Of course, for both of those pathogens, there is a Western market. There is no Western market for a TB vaccine.” +
++Since then, however, there have been renewed efforts to eradicate TB. The emergence of drug-resistant TB has threatened to reverse what global gains against TB have been made and may even cause a TB resurgence in the US and other low-burden countries, spurring more attention and funding to the disease. The Global Fund and the Stop TB Partnership have also launched major advocacy campaigns to bring more attention to the epidemic. +
++Additionally, in 2016, the World Health Organization set a goal to end the TB epidemic by 2030. The US government has also ramped up investments in global TB eradication efforts. In the 2023 fiscal year, the US contributed more than $400 million to the cause, nearly double its total investments for global TB in fiscal year 2013. +
++As of last year, there are 16 new TB vaccine candidates in development, four of which are in phase 3 clinical trials — which, if successful, would likely be the last phase of trials before FDA or WHO approval. Some vaccines aim to replace the BCG vaccine altogether while other candidates will serve as boosters to the BCG vaccine among adolescents and adults, McShane explained. +
++One vaccine, M72/AS01E, seems to be the most promising candidate, buoyed by support and funding from the Bill and Melinda Gates Foundation. In a phase 2B clinical trial conducted in South Africa, Kenya, and Zambia, more than 3,500 adults with latent TB were randomly assigned to receive either two doses of the M72/AS01E vaccine or a placebo. Initial vaccine efficacy was 54 percent. Three years later, a follow-up analysis revealed that the vaccine had prevented active TB cases in 49.7 percent of people who received the vaccine. +
++Most other TB vaccine candidates have demonstrated similar efficacy rates. “It’s unlikely that we’re going to get a vaccine against tuberculosis that is 100 percent effective anytime soon,” McShane said. +
++But even a TB vaccine with low efficacy can have profound global implications. If the M72/AS01E vaccine demonstrates safety and efficacy in the ongoing phase 3 trial, then for the first time, the world could prevent at least a good portion of infections among adolescents and adults. +
++“One of the big issues is that even if we’ll have a vaccine, it’ll be a game changer, but the effectiveness is around 50 percent. So it’s not one of the best, but it is something,” said Eliud Wandwalo, head of TB at the Global Fund to Fight AIDS, Tuberculosis and Malaria. +
++Given the relatively low efficacy rates, these new TB vaccines are not a silver bullet for eradicating TB globally. For most of the world, improvements in sanitation, infrastructure, and medication are also urgently needed. Currently, it takes six months of ongoing therapy to cure TB, and as drug-resistant strains of TB become more common, existing antibiotics will become less and less useful. The vaccine will be just one of the tools in the toolbox, Wandwalo said. +
++“If you look at the trajectory and projections, if we continue the same pace with the same tools, we’ll be ending TB in the next 180 years,” he said. “It’s a dire projection. But I think with a vaccine, we are likely to be able to end TB in our lifetime.” +
++
+How conspiring doctors, questionable tonics, and twisted patriotism led to the 1864 Arizona abortion ban that was just upheld in court. +
++Earlier this week, the Arizona Supreme Court ruled that a Civil War-era state law that amounts to a near-total ban on abortion can be enforced, putting access to reproductive care for about 1.6 million people of reproductive age under immediate threat. +
++It’s one of several abortion laws enacted before the Supreme Court’s 1973 decision in Roe v. Wade that have been revived since the justices overturned Roe in 2022. Resuscitating these laws has created legal headaches, in part because they were written in a very different time for reasons that have little in common with the concerns of anti-abortion advocates today. +
++Arizona’s ban, first passed in 1864 and codified again in 1901 and 1913, says anyone who “provides, supplies or administers” an abortion or abortion drugs will face a state prison sentence of two to five years unless the abortion is necessary to save the life of the person who is pregnant. Taken out of the 19th-century context in which it was passed, that language would seem to amount to a near-total ban on abortion. +
++But that’s not how the law was originally enforced. Few people were prosecuted under the Arizona law or similar ones in other states. At the time, first-trimester abortions were widespread and widely accepted in the public conscience. +
++Abortion laws of the mid-1800s were the product of discussions among lawyers and doctors and were designed to professionalize abortion services and medicine writ large — a seemingly noble cause, but also one driven by physicians’ self-interests and the desire to both boost (white) women’s birth rates and weaken a nascent feminist movement. +
++There was no national abortion debate to speak of. Religion wasn’t yet a major factor in Americans’ views on abortion in the way it is today, and scientists had not yet developed methods to detect pregnancy during the first months of gestation. +
++All of that meant abortion was a common, if not always safe, part of American life, despite what the old laws might suggest. +
++“I think people imagine nobody did it because it was illegal. But we know that’s not true,” said Lauren MacIvor Thompson, a history professor at Kennesaw State University focusing on women’s rights and public health. +
++For much of the first half of the 19th century, there were few laws in the US that were specifically concerned with abortion. Rather, abortion was understood in the tradition of British common law: It was only a crime after “quickening,” when a fetus’s movement could be detected — around four or five months of gestation. Before quickening, people could be ignorant (or have plausible deniability) about being pregnant. +
++Generally, the American public at this time had few moral qualms about abortion before quickening. In particular, it was a service that many believed should be offered to unmarried women, who risked reputational ruin if they proceeded with the pregnancy and often came from poor backgrounds, as historian James Mohr writes in his 1978 book, Abortion in America. +
++But around the mid-1800s, things started to shift. More people appeared to be seeking abortions, not just those who were unmarried. One estimate by physicians at the time that Mohr cites suggests that as many as one in five pregnancies ended in abortion. Partially because of this, birth rates fell dramatically: from 7.04 children per woman in 1800 to 3.56 by 1900, according to Mohr. +
++Starting around the 1830s, abortion became a lucrative industry. It was still mostly unregulated but perceived as largely safe, especially when weighed against the risks of pregnancy. There is little available data on maternal mortality rates in the US at the time, but even by 1915, after the development of antisepsis, it was about 600 in every 100,000 births — higher than in some European countries at the time. In 2021, the US maternal mortality rate was 32.9 deaths per 100,000 live births. +
++As Mohr writes, home medical manuals and midwifery texts advised readers on abortifacient substances (such as black hellebore) and practices that could bring about an abortion (such as bloodletting and “raising great weights”). Abortifacient tonics of varying effectiveness were prolifically advertised. Physicians, midwives, and even untrained practitioners offered procedures to clear “obstructed menses.” One abortion provider to the elites, known as “Madame Restell,” amassed a fortune estimated at up to $1 million. +
++Increased access to abortion seen throughout the 19th century led to increased scrutiny, however, and that led to many of the laws and attitudes still with us today. +
++The anti-abortion movement began to take off in the 1850s for a few reasons. +
++For one, anti-abortionists resented the fact that wealthy, white Protestant women were starting to drive demand for abortions, usually to limit their family size or delay having their first child. +
++These women were seen as shirking their duties to “republican motherhood” — a concept that involved raising the next generation of productive citizens instilled with the values espoused by the young American republic and that excluded nonwhite women. They were maligned for indulging priorities outside of the home at a time when the women’s suffrage movement was taking shape. Some men were seen as complicit in this phenomenon, urging their wives to get abortions and paying for them. +
++Anti-abortionists argued that laws specifically restricting abortion were necessary because otherwise, “nice white ladies who don’t want to be pregnant just won’t fulfill their obligation,” as MacIvor Thompson put it. +
++Around this time, there were also a few highly publicized trials involving botched abortions, typically cases where the pregnant person died. This raised the profile of abortion as a safety issue for legislators. +
++A broader movement to professionalize the American medical system also contributed to the first laws restricting abortion in the US. The Civil War laid bare the need for more competent medical professionals, and credentialed physicians known as “regulars” lobbied for laws on abortion for the stated reason of protecting people from quacks. +
++But they also had selfish motivations to essentially establish a monopoly over the market for abortions and sideline their competition. Physicians — who, at that point, were nearly all white and male — had lost income and stature as a result of this competition with other medical practitioners, and performing abortions was a way to attract loyal long-term patients, Mohr writes. +
++“What they’re trying to do is consolidate their professional dominance because they don’t want to be competing with midwives or competing with what they call ‘the irregulars,’” MacIvor Thompson said. This was despite the fact, she added, that the “outcomes that doctors got in terms of treating patients were really not that much better than people who didn’t have medical training.” +
++The first standalone law to specifically prohibit abortion in the US was passed in Massachusetts in 1845. It made performing an abortion a misdemeanor for which an offender could serve five to seven years in jail and face up to a $2,000 fine — about $74,000 in 2024 dollars — or a felony in cases where the person having the procedure died. +
++But as would be the case with others that came after it, the law was rarely enforced: No one was convicted under it between 1849 and 1857, according to Mohr. Generally, such early abortion laws mostly did not create penalties for the pregnant person who sought an abortion but only for those who performed them — and messed up. +
++“Historians have argued that a lot of these initial laws were meant to protect women. They’re either next to poisoning laws, or they’re framed in a way where it’s like, this is to protect women from quacks,” said Shannon Withycombe, a history professor at the University of New Mexico who studies early abortion laws. +
++Few religious leaders wanted to get involved in abortion politics. Some Catholic bishops espoused the position, as the church does now, that abortion is wrong because life begins at conception. But at the time, Catholicism was associated with European immigrants who weren’t “welcomed into white middle-class American society,” MacIvor Thompson said. +
++However, Horatio Storer, a Harvard physician who converted to Catholicism in his 40s, set out to consolidate support for anti-abortion laws in the 1850s. He ultimately led the charge to criminalize those who sought abortions and to make the punishment more severe if the person was married. He even pushed physicians and legislators to abandon the earlier understanding of abortion as acceptable before quickening and to suppress it at any stage of pregnancy. +
++Storer’s writings came to inform anti-abortion legislation across the country, though the physician lobby didn’t agree with everything he wrote. Many believed he had gone too far in framing abortion as a religious and moral issue, insisting that it was really a medical issue, Withycombe said. +
++But physicians latched on to one particular point Storer made in his 1860 book On Criminal Abortion in America: that “doctors need to be able to practice abortion because there are lots of reasons why an abortion is important for the health and life of a woman,” Withycombe said. +
++This supported physicians as the definitive source of medical expertise about when and how an abortion should be safely administered over other abortion practitioners. And Withycombe notes that in her readings of medical articles and obstetrical teaching texts of the time, she has found a broad array of circumstances in which physicians believed it was their medical duty to perform an abortion — including circumstances in which failing to do so wouldn’t necessarily result in a pregnant person’s death, such as “pernicious anemia,” “obstinate vomiting,” and “advancing jaundice.” +
++Withycombe said the 1864 Arizona law was part of a wave of legislation, all with similar provisions informed by Storer’s writings, that swept the West in the 1860s while the Civil War was raging. Colorado passed a ban in 1861, Nevada in 1861, Idaho in 1864, and Montana in 1864. At the time, these states were trying to prove that they were part of modern America, emulating medical licensing laws and protections that had already been enacted in more cosmopolitan parts of the country. +
++In that sense, the passage of these laws was more about professionalizing medicine than the moralistic arguments that later motivated the 1873 Comstock Act, a federal anti-obscenity law that also prohibited the mailing of “every article or thing designed, adapted, or intended for producing abortion.” +
++However, Storer’s moral philosophy on abortion did eventually gain traction, and it influenced the next wave of anti-abortion lawmaking in the decades thereafter. About 40 states banned abortion by 1880. +
++Arizona isn’t alone in dealing with a pre-Roe anti-abortion law. Oklahoma is currently enforcing a 1910 abortion ban. Wisconsin’s Democratic attorney general has asked the state Supreme Court to strike down that state’s 1849 ban. Delaware, New Mexico, and Michigan have repealed their pre-Roe bans only in the last few years. West Virginia’s 19th-century ban was blocked in court in 2022, but the state legislature moved quickly to codify a new abortion ban that allows few exceptions. +
++The Arizona ban won’t go into effect until at least April 24 under the court’s ruling Tuesday. In the meantime, Democrats in the state legislature want to repeal the law and Republicans have stymied their attempts to do so. +
++As part of the ruling, the state must ensure the 19th-century law is “harmonized” with a ban after 15 weeks of pregnancy passed in March 2022. It’s not yet clear, however, what that means in practice. +
++Arizona Attorney General Kris Mayes, a Democrat, has indicated she would not enforce the 1864 ban. Even limited enforcement would look very different from the way the law was interpreted in the years immediately after its passage. +
++As mentioned, enforcement was spotty in the 19th century, and unlike now, abortion providers continued to operate despite facing potential legal repercussions. Producers of abortifacients often circumvented bans by using euphemistic language to describe their products. +
++Early abortion laws, including the Arizona ban, also empowered physicians to make decisions about abortion. “A lot of these laws were at least supported if not written by physicians,” Withycombe said. “Physicians agreed that they have complete discretion over whether an abortion is medically necessary.” +
++However, doctors have often been sidelined in the enforcement of abortion bans post-Roe, with many choosing to leave states with restrictive laws because they feel they cannot perform lifesaving care. +
++The medical and popular understanding of pregnancy and abortion has also evolved since 1864. We can now detect pregnancy much earlier than “quickening” using urine and blood tests. In the 1860s, early abortions were generally seen as morally equivalent to contraception, Mohr writes — a concept that the American right largely rejects today. +
++“These laws are being upheld as proof that everyone was completely against abortion in all cases, from the moment of conception,” Withycombe said. “Given the understanding of human development at the time, that is not true in the 1860s.” +
IPL-17: MI vs CSK | Mumbai Indians win toss; elect to bowl against Chennai Super Kings - Mumbai Indians are unchanged while Chennai Super Kings brought in Pathirana in place of Theekshana.
Arjun Kadhe and Jeevan Nedunchezhiyan clinch Challenger in Mexico - Cuernavaca (Mexico)
IPL-17: KKR vs LSG | Salt, Narine shine as Kolkata Knight Riders thrash Lucknow Super Giants - Both the teams made one change to its playing XI.
Twenty20 World Cup | I want to be at my best through IPL experience, says Travis Head - Travis Head showed his adaptive skills while playing for Sunrisers Hyderabad in the ongoing IPL.
IPL-17: RCB vs SRH | Focus on bowlers as Royal Challengers Bengaluru aim for elusive victory against Sunrisers Hyderabad - The Royal Challengers have players of repute and elite coaches with lofty pedigree but none of their plans have worked so far, evidenced by the team’s 10th place in the standings
Man held for posing as cop and promising police jobs to aspirants -
Tributes paid to confiscated Amedkar statue -
Modi accuses INDIA alliance of trying to finish Sanatan dharma - Congress dividing and weakening the country with its dangerous ideas: PM
Minister Peddireddi suspects conspiracy behind attack on Jagan - He accuses TDP of conspiring to attack Chief Minister Y.S. Jagan Mohan Reddy adding the attack was pre-planned
BJP leader calls upon people to realise the ideals espoused by Ambedkar - PM Modi dedicates himself to implementing what Dr. Ambedkar had conceived, and he has been largely successful in doing it, says Shekhar Rao Perala
Russian double-tap strikes hit civilians then rescuers too - Russia is following up initial attacks with repeat strikes targeting rescuers treating the wounded.
Ukraine could face defeat in 2024. Here’s how that might look - With ammo critically low and Western aid stalled, what might Russia attempt in Ukraine this year?
BBC Russian journalist branded ‘foreign agent’ - A leading science journalist - Asya Kazantseva - also gets the label used to silence Kremlin critics.
Russia floods leave houses almost submerged - Water levels in Orenburg are 2m above critical levels, as the mayor urges mass evacuations.
Italian fashion designer Roberto Cavalli dies - The designer, famed for his animal prints on leather and textiles, died at home in Florence.
Sleeping more flushes junk out of the brain - Rhythmic activity during sleep may get fluids in the brain moving. - link
Why do some people always get lost? - Experience may matter more than innate ability when it comes to sense of direction. - link
Change Healthcare faces another ransomware threat—and it looks credible - Hackers already received a $22 million payment. Now a second group demands money. - link
How new tech is making geothermal energy a more versatile power source - Geothermal has moved beyond being confined to areas with volcanic activity. - link
US drug shortages reach record high with 323 meds now in short supply - The shortages affect everything from generic cancer drugs to ADHD medication. - link
My snooty friend always uses French words like hors d’oeuvres in his day-to-day conversation. -
++And that’s just…for starters. +
+ submitted by /u/porichoygupto
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Why was Heisenberg’s wife always sad? -
++Because when he had the position, he didn’t have the momentum, and when he had the momentum, he didn’t have the position. +
+ submitted by /u/SLC2ATX
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The prostitute put on her clothes and said… -
++… “It was a business doing pleasure with you.” +
+ submitted by /u/MrDagon007
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Proctologist… -
++A man goes to a proctologist for his bi-annual prostate exam. After the procedure the doctor tells the man his prostate indeed felt enlarged. +
++“Wait a minute, doc! I’ve been doing everything right lately!”, the man protests. “I eat healthy, I exercise— I want a second opinion!” +
++So the doctor bends him over again and uses two fingers. +
+ submitted by /u/jseyfer
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Boy and his dad were driving home from the ice cream shop when the boy asks, ’Why is my sister called Teresa?" “It’s because your mom loves Easter and Teresa is an anagram of Easter.” -
++“Oh. Thanks dad.” +
++“You’re welcome Alan.” +
+ submitted by /u/ResinJones76
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