7022. Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial.
Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications.
7023. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.
作者: Melanie Davies.;Louise Færch.;Ole K Jeppesen.;Arash Pakseresht.;Sue D Pedersen.;Leigh Perreault.;Julio Rosenstock.;Iichiro Shimomura.;Adie Viljoen.;Thomas A Wadden.;Ildiko Lingvay.; .
来源: Lancet. 2021年397卷10278期971-984页
This trial assessed the efficacy and safety of the GLP-1 analogue once a week subcutaneous semaglutide 2·4 mg versus semaglutide 1·0 mg (the dose approved for diabetes treatment) and placebo for weight management in adults with overweight or obesity, and type 2 diabetes.
7024. Alzheimer's disease.
作者: Philip Scheltens.;Bart De Strooper.;Miia Kivipelto.;Henne Holstege.;Gael Chételat.;Charlotte E Teunissen.;Jeffrey Cummings.;Wiesje M van der Flier.
来源: Lancet. 2021年397卷10284期1577-1590页
In this Seminar, we highlight the main developments in the field of Alzheimer's disease. The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease. The earliest phase of Alzheimer's disease (cellular phase) happens in parallel with accumulating amyloid β, inducing the spread of tau pathology. The risk of Alzheimer's disease is 60-80% dependent on heritable factors, with more than 40 Alzheimer's disease-associated genetic risk loci already identified, of which the APOE alleles have the strongest association with the disease. Novel biomarkers include PET scans and plasma assays for amyloid β and phosphorylated tau, which show great promise for clinical and research use. Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia. Lifestyle factors do not directly affect Alzheimer's disease pathology, but can still contribute to a positive outcome in individuals with Alzheimer's disease. Promising pharmacological treatments are poised at advanced stages of clinical trials and include anti-amyloid β, anti-tau, and anti-inflammatory strategies.
7026. Guillain-Barré syndrome.
Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Most patients present with an antecedent illness, most commonly upper respiratory tract infection, before the onset of progressive motor weakness. Several microorganisms have been associated with Guillain-Barré syndrome, most notably Campylobacter jejuni, Zika virus, and in 2020, the severe acute respiratory syndrome coronavirus 2. In C jejuni-related Guillain-Barré syndrome, there is good evidence to support an autoantibody-mediated immune process that is triggered by molecular mimicry between structural components of peripheral nerves and the microorganism. Making a diagnosis of so-called classical Guillain-Barré syndrome is straightforward; however, the existing diagnostic criteria have limitations and can result in some variants of the syndrome being missed. Most patients with Guillain-Barré syndrome do well with immunotherapy, but a substantial proportion are left with disability, and death can occur. Results from the International Guillain-Barré Syndrome Outcome Study suggest that geographical variations exist in Guillain-Barré syndrome, including insufficient access to immunotherapy in low-income countries. There is a need to provide improved access to treatment for all patients with Guillain-Barré syndrome, and to develop effective disease-modifying therapies that can limit the extent of nerve injury. Clinical trials are currently underway to investigate some of the potential therapeutic candidates, including complement inhibitors, which, together with emerging data from large international collaborative studies on the syndrome, will contribute substantially to understanding the many facets of this disease.
7028. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations.
Endometriosis is a common disease affecting 5-10% of women of reproductive age globally. However, despite its prevalence, diagnosis is typically delayed by years, misdiagnosis is common, and delivery of effective therapy is prolonged. Identification and prompt treatment of endometriosis are essential and facilitated by accurate clinical diagnosis. Endometriosis is classically defined as a chronic, gynaecological disease characterised by endometrial-like tissue present outside of the uterus and is thought to arise by retrograde menstruation. However, this description is outdated and no longer reflects the true scope and manifestations of the disease. The clinical presentation is varied, the presence of pelvic lesions is heterogeneous, and the manifestations of the disease outside of the female reproductive tract remain poorly understood. Endometriosis is now considered a systemic disease rather than a disease predominantly affecting the pelvis. Endometriosis affects metabolism in liver and adipose tissue, leads to systemic inflammation, and alters gene expression in the brain that causes pain sensitisation and mood disorders. The full effect of the disease is not fully recognised and goes far beyond the pelvis. Recognition of the full scope of the disease will facilitate clinical diagnosis and allow for more comprehensive treatment than currently available. Progestins and low-dose oral contraceptives are unsuccessful in a third of symptomatic women globally, probably as a result of progesterone resistance. Oral gonadotropin-releasing hormone (GnRH) antagonists constitute an effective and tolerable therapeutic alternative when first-line medications do not work. The development of GnRH antagonists has resulted in oral drugs that have fewer side-effects than other therapies and has allowed for rapid movement between treatments to optimise and personalise endometriosis care. In this Review, we discuss the latest understanding of endometriosis as a systemic disease with multiple manifestations outside the parameters of classic gynaecological disease.
7029. The inverse care law re-examined: a global perspective.
作者: Richard Cookson.;Tim Doran.;Miqdad Asaria.;Indrani Gupta.;Fiorella Parra Mujica.
来源: Lancet. 2021年397卷10276期828-838页
An inverse care law persists in almost all low-income and middle-income countries, whereby socially disadvantaged people receive less, and lower-quality, health care despite having greater need. By contrast, a disproportionate care law persists in high-income countries, whereby socially disadvantaged people receive more health care, but of worse quality and insufficient quantity to meet their additional needs. Both laws are caused not only by financial barriers and fragmented health insurance systems but also by social inequalities in care seeking and co-investment as well as the costs and benefits of health care. Investing in more integrated universal health coverage and stronger primary care, delivered in proportion to need, can improve population health and reduce health inequality. However, trade-offs sometimes exist between health policy objectives. Health-care technologies, policies, and resourcing should be subjected to distributional analysis of their equity impacts, to ensure the objective of reducing health inequalities is kept in sight.
7030. Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa.
作者: David Bath.;Jackie Cook.;John Govere.;Phillemon Mathebula.;Natashia Morris.;Khumbulani Hlongwana.;Jaishree Raman.;Ishen Seocharan.;Alpheus Zitha.;Matimba Zitha.;Aaron Mabuza.;Frans Mbokazi.;Elliot Machaba.;Erik Mabunda.;Eunice Jamesboy.;Joseph Biggs.;Chris Drakeley.;Devanand Moonasar.;Rajendra Maharaj.;Maureen Coetzee.;Catherine Pitt.;Immo Kleinschmidt.
来源: Lancet. 2021年397卷10276期816-827页
Increasing insecticide costs and constrained malaria budgets could make universal vector control strategies, such as indoor residual spraying (IRS), unsustainable in low-transmission settings. We investigated the effectiveness and cost-effectiveness of a reactive, targeted IRS strategy.
7031. Impact and cost-effectiveness of a lethal house lure against malaria transmission in central Côte d'Ivoire: a two-arm, cluster-randomised controlled trial.
作者: Eleanore D Sternberg.;Jackie Cook.;Ludovic P Ahoua Alou.;Serge Brice Assi.;Alphonsine A Koffi.;Dimi T Doudou.;Carine J Aoura.;Rosine Z Wolie.;Welbeck A Oumbouke.;Eve Worrall.;Immo Kleinschmidt.;Raphael N'Guessan.;Matthew B Thomas.
来源: Lancet. 2021年397卷10276期805-815页
New vector control tools are required to sustain the fight against malaria. Lethal house lures, which target mosquitoes as they attempt to enter houses to blood feed, are one approach. Here we evaluated lethal house lures consisting of In2Care (Wageningen, Netherlands) Eave Tubes, which provide point-source insecticide treatments against host-seeking mosquitoes, in combination with house screening, which aims to reduce mosquito entry.
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