Riviste scientifiche

[Comment] Immune checkpoint inhibition in urothelial carcinoma

The Lancet - Sa, 16/05/2020 - 00:00
Immune checkpoint inhibitors such as atezolizumab have had a major positive effect on the treatment of platinum-refractory advanced urothelial carcinoma.1 Non-randomised trials have shown efficacy in patients with front-line programmed cell death ligand 1 (PD-L1) biomarker-positive advanced urothelial carcinoma, but there has not yet been a transformative change to treatment because of insufficient randomised trial data.2–4 These insufficient data are not due to a lack of randomised studies—at least six are ongoing.

[Comment] Adjuvant nivolumab plus ipilimumab for resected stage IV melanoma

The Lancet - Sa, 16/05/2020 - 00:00
Combined immune checkpoint inhibitor therapy with monoclonal antibodies against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) is associated with high response rates and high toxicity in patients with unresectable stage III and stage IV melanoma (henceforth referred to as advanced melanoma).1 In the CheckMate-067 trial, previously untreated patients with advanced melanoma were randomly assigned to one of three groups: combination of ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) induction followed by nivolumab maintenance, nivolumab monotherapy, and ipilimumab monotherapy.

[Comment] Increasing the visibility of older women in clinical research

The Lancet - Sa, 16/05/2020 - 00:00
By 2024, more than 20% of Canada's population will be 65 years or older, joining other countries in becoming a super-aged society.1,2 The USA and the UK are also among the high-income countries that will soon follow in becoming super-aged nations.2 In all three countries, the majority of those in this older age group will be women, with their proportion increasing with advancing age (figure).

[Comment] Offline: Don't let COVID-19 divert us completely

The Lancet - Sa, 16/05/2020 - 00:00
Dr Robert Spencer, a trustee of Dr Edward Jenner's House, Garden and Museum in Berkeley, Gloucestershire, UK, wrote to me last week on the 40th anniversary of the eradication of smallpox (May 8). He was polite but disappointed: “On this day in 1980 the WHO announced the eradication of smallpox from the world. This infection, which probably caused more deaths than any other disease, was finally condemned to the history books. Sorry to see you had no space in this week's edition of The Lancet to commemorate this milestone, especially at a time of COVID-19 pandemic.” Dr Spencer was right to admonish me.

[World Report] In the aftermath: the legacy of measles in Samoa

The Lancet - Sa, 16/05/2020 - 00:00
As Samoa recovers from a devastating measles outbreak, Jacqui Thornton reports on how the epidemic is having long-lasting effects on the country's health system.

[Perspectives] Computer vision's potential to improve health care

The Lancet - Sa, 16/05/2020 - 00:00
Artificial intelligence (AI) research for medical applications has largely focused on image pattern recognition or electronic health record (EHR) data. EHR data inputs include what clinicians order and what they document that they did. But the physical actions that comprise what clinicians actually did for patients can differ: one study showed almost half of physician medical record entries documenting the extent of their physical examinations of emergency room patients were not substantiated by an independent physician observer.

[Perspectives] Trial and error

The Lancet - Sa, 16/05/2020 - 00:00
Two decades ago, the estimation that a jumbo jet's worth of Americans were tumbling out of the skies every single day due to our medical errors grabbed headlines and jumpstarted the modern patient safety movement. To Err is Human—the seminal report on medical error from the Institute of Medicine, now the US National Academy of Medicine—detonated like a bomb. Ever since then, the medical world has been scrambling to find ways to decrease medical error and improve patient safety. Hospital systems have been redesigned.

[Obituary] Martin Khor Kok Peng

The Lancet - Sa, 16/05/2020 - 00:00
Economist and champion of social justice and the Global South. He was born in Penang, Malaysia, on Nov 9, 1951, and died of cancer in Penang on April 1, 2020, aged 68 years.

[Articles] Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial

The Lancet - Sa, 16/05/2020 - 00:00
Addition of atezolizumab to platinum-based chemotherapy as first-line treatment prolonged progression-free survival in patients with metastatic urothelial carcinoma. The safety profile of the combination was consistent with that observed with the individual agents. These results support the use of atezolizumab plus platinum-based chemotherapy as a potential first-line treatment option for metastatic urothelial carcinoma.

[Articles] Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial

The Lancet - Sa, 16/05/2020 - 00:00
Adjuvant therapy with nivolumab alone or in combination with ipilimumab increased recurrence-free survival significantly compared with placebo in patients with stage IV melanoma with no evidence of disease. The rates of grade 3–4 treatment-related adverse events in both active treatment groups were higher than the rates reported in previous pivotal trials done in advanced melanoma with measurable disease.

[Clinical Picture] Full neurological recovery 6 h after cardiac arrest due to accidental hypothermia

The Lancet - Sa, 16/05/2020 - 00:00
A 34-year-old woman who collapsed during a mountain trek in northern Spain was initially assessed at an emergency rescue centre. She was unresponsive, asystolic, and pulseless, had unreactive dilated pupils, and had a tympanic temperature of 18°C. Advanced life support was started, and the woman was transferred to our hospital. She arrived 2 h and 25 min after the first evaluation—she was still in asystole, had unreactive dilated pupils, and had a core temperature of 20·2°C. An arterial blood sample showed a pH of 6·81, a lactate concentration of 10·3 mmol/L (normal 0·5–1), and a potassium concentration of 4·4 mmol/L (normal 3·5–5).

[Review] Artificial intelligence and the future of global health

The Lancet - Sa, 16/05/2020 - 00:00
Concurrent advances in information technology infrastructure and mobile computing power in many low and middle-income countries (LMICs) have raised hopes that artificial intelligence (AI) might help to address challenges unique to the field of global health and accelerate achievement of the health-related sustainable development goals. A series of fundamental questions have been raised about AI-driven health interventions, and whether the tools, methods, and protections traditionally used to make ethical and evidence-based decisions about new technologies can be applied to AI.

Spatiotemporal trends and ecological determinants in maternal mortality ratios in 2,205 Chinese counties, 2010–2013: A Bayesian modelling analysis

PLoS Medicine - Ve, 15/05/2020 - 23:00

by Junming Li, Juan Liang, Jinfeng Wang, Zhoupeng Ren, Dian Yang, Yanping Wang, Yi Mu, Xiaohong Li, Mingrong Li, Yuming Guo, Jun Zhu

Background

As one of its Millennium Development Goals (MDGs), China has achieved a dramatic reduction in the maternal mortality ratio (MMR), although a distinct spatial heterogeneity still persists. Evidence of the quantitative effects of determinants on MMR in China is limited. A better understanding of the spatiotemporal heterogeneity and quantifying determinants of the MMR would support evidence-based policymaking to sustainably reduce the MMR in China and other developing areas worldwide.

Methods and findings

We used data on MMR collected by the National Maternal and Child Health Surveillance System (NMCHSS) at the county level in China from 2010 to 2013. We employed a Bayesian space–time model to investigate the spatiotemporal trends in the MMR from 2010 to 2013. We used Bayesian multivariable regression and GeoDetector models to address 3 main ecological determinants of the MMR, including per capita income (PCI), the proportion of pregnant women who delivered in hospitals (PPWDH), and the proportion of pregnant women who had at least 5 check-ups (PPWFC). Among the 2,205 counties, there were 925 (42.0%) hotspot counties, located mostly in China’s western and southwestern regions, with a higher MMR, and 764 (34.6%) coldspot counties with a lower MMR than the national level. China’s westernmost regions, including Tibet and western Xinjiang, experienced a weak downward trend over the study period. Nationwide, medical intervention was the major determinant of the change in MMR. The MMR decreased by 1.787 (95% confidence interval [CI]: 1.424–2.142, p < 0.001) per 100,000 live births when PPWDH increased by 1% and decreased by 0.623 (95% CI 0.436–0.798, p < 0.001) per 100,000 live births when PPWFC increased by 1%. The major determinants for the MMR in China’s western and southwestern regions were PCI and PPWFC, while that in China’s eastern and southern coastlands was PCI. The MMR in western and southwestern regions decreased nonsignificantly by 1.111 (95% CI −1.485–3.655, p = 0.20) per 100,000 live births when PCI in these regions increased by 1,000 Chinese Yuan and decreased by 1.686 (95% CI 1.275–2.090, p < 0.001) when PPWFC increased by 1%. Additionally, the western and southwestern regions showed the strongest interactive effects between different factors, in which the corresponding explanatory power of any 2 interacting factors reached up to greater than 80.0% (p < 0.001) for the MMR. Limitations of this study include a relatively short study period and lack of full coverage of eastern coastlands with especially low MMR.

Conclusions

Although China has accomplished a 75% reduction in the MMR, spatial heterogeneity still exists. In this study, we have identified 925 (hotspot) high-risk counties, mostly located in western and southwestern regions, and among which 332 counties are experiencing a slower pace of decrease than the national downward trend. Nationally, medical intervention is the major determinant. The major determinants for the MMR in western and southwestern regions, which are developing areas, are PCI and PPWFC, while that in China’s developed areas is PCI. The interactive influence of any two of the three factors, PCI, PPWDH, and PPWFC, in western and southwestern regions was up to and in excess of 80% (p < 0.001).

Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study

PLoS Medicine - Ve, 15/05/2020 - 23:00

by Casper Reijnen, Evangelia Gogou, Nicole C. M. Visser, Hilde Engerud, Jordache Ramjith, Louis J. M. van der Putten, Koen van de Vijver, Maria Santacana, Peter Bronsert, Johan Bulten, Marc Hirschfeld, Eva Colas, Antonio Gil-Moreno, Armando Reques, Gemma Mancebo, Camilla Krakstad, Jone Trovik, Ingfrid S. Haldorsen, Jutta Huvila, Martin Koskas, Vit Weinberger, Marketa Bednarikova, Jitka Hausnerova, Anneke A. M. van der Wurff, Xavier Matias-Guiu, Frederic Amant, ENITEC Consortium , Leon F. A. G. Massuger, Marc P. L. M. Snijders, Heidi V. N. Küsters-Vandevelde, Peter J. F. Lucas, Johanna M. A. Pijnenborg

Background

Bayesian networks (BNs) are machine-learning–based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node metastasis (LNM) is challenging in endometrial cancer, and although several biomarkers are related to LNM, none of them are incorporated in clinical practice. The aim of this study was to develop and externally validate a preoperative BN to predict LNM and outcome in endometrial cancer patients.

Methods and findings

Within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), we performed a retrospective multicenter cohort study including 763 patients, median age 65 years (interquartile range [IQR] 58–71), surgically treated for endometrial cancer between February 1995 and August 2013 at one of the 10 participating European hospitals. A BN was developed using score-based machine learning in addition to expert knowledge. Our main outcome measures were LNM and 5-year disease-specific survival (DSS). Preoperative clinical, histopathological, and molecular biomarkers were included in the network. External validation was performed using 2 prospective study cohorts: the Molecular Markers in Treatment in Endometrial Cancer (MoMaTEC) study cohort, including 446 Norwegian patients, median age 64 years (IQR 59–74), treated between May 2001 and 2010; and the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study cohort, including 384 Dutch patients, median age 66 years (IQR 60–73), treated between September 2011 and December 2013. A BN called ENDORISK (preoperative risk stratification in endometrial cancer) was developed including the following predictors: preoperative tumor grade; immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, and L1 cell adhesion molecule (L1CAM); cancer antigen 125 serum level; thrombocyte count; imaging results on lymphadenopathy; and cervical cytology. In the MoMaTEC cohort, the area under the curve (AUC) was 0.82 (95% confidence interval [CI] 0.76–0.88) for LNM and 0.82 (95% CI 0.77–0.87) for 5-year DSS. In the PIPENDO cohort, the AUC for 5-year DSS was 0.84 (95% CI 0.78–0.90). The network was well-calibrated. In the MoMaTEC cohort, 249 patients (55.8%) were classified with <5% risk of LNM, with a false-negative rate of 1.6%. A limitation of the study is the use of imputation to correct for missing predictor variables in the development cohort and the retrospective study design.

Conclusions

In this study, we illustrated how BNs can be used for individualizing clinical decision-making in oncology by incorporating easily accessible and multimodal biomarkers. The network shows the complex interactions underlying the carcinogenetic process of endometrial cancer by its graphical representation. A prospective feasibility study will be needed prior to implementation in the clinic.

Ethnic disparities in initiation and intensification of diabetes treatment in adults with type 2 diabetes in the UK, 1990–2017: A cohort study

PLoS Medicine - Ve, 15/05/2020 - 23:00

by Rohini Mathur, Ruth E. Farmer, Sophie V. Eastwood, Nish Chaturvedi, Ian Douglas, Liam Smeeth

Background

Type 2 diabetes mellitus (T2DM) disproportionately affects individuals of nonwhite ethnic origin. Timely and appropriate initiation and intensification of glucose-lowering therapy is key to reducing the risk of major vascular outcomes. Given that ethnic inequalities in outcomes may stem from differences in therapeutic management, the aim of this study was to identify ethnic differences in the timeliness of initiation and intensification of glucose-lowering therapy in individuals newly diagnosed with T2DM in the United Kingdom.

Methods and findings

An observational cohort study using the Clinical Practice Research Datalink was conducted using 162,238 adults aged 18 and over diagnosed with T2DM between 1990 and 2017 (mean age 62.7 years, 55.2% male); 93% were of white ethnicity (n = 150,754), 5% were South Asian (n = 8,139), and 2.1% were black (n = 3,345). Ethnic differences in time to initiation and intensification of diabetes treatment were estimated at three time points (initiation of noninsulin monotherapy, intensification to noninsulin combination therapy, and intensification to insulin therapy) using multivariable Cox proportional hazards regression adjusted for factors a priori hypothesised to be associated with initiation and intensification: age, sex, deprivation, glycated haemoglobin (HbA1c), body mass index (BMI), smoking status, comorbidities, consultations, medications, calendar year, and clustering by practice. Odds of experiencing therapeutic inertia (failure to intensify treatment within 12 months of HbA1c >7.5% [58 mmol/mol]), were estimated using multivariable logistic regression adjusted for the same hypothesised confounders. Noninsulin monotherapy was initiated earlier in South Asian and black groups (South Asian HR 1.21, 95% CI 1.08–1.36, p < 0.001; black HR 1.29, 95% CI 1.05–1.59, p = 0.017). Correspondingly, no ethnic differences in therapeutic inertia were evident at initiation. Intensification with noninsulin combination therapy was slower in both nonwhite ethnic groups relative to white (South Asian HR 0.80, 95% CI 0.74–0.87, p < 0.001; black HR 0.79, 95% CI 0.70–0.90, p < 0.001); treatment inertia at this stage was greater in nonwhite groups relative to white (South Asian odds ratio [OR] 1.45, 95% CI 1.23–1.70, p < 0.001; black OR 1.43, 95% CI 1.09–1.87, p = 0.010). Intensification to insulin therapy was slower again for black groups relative to white groups (South Asian HR 0.49, 95% CI 0.41–0.58, p < 0.001; black HR 0.69, 95% CI 0.53–0.89, p = 0.012); correspondingly, treatment inertia was significantly higher in nonwhite groups at this stage relative to white groups (South Asian OR 2.68, 95% CI 1.89–3.80 p < 0.001; black OR 1.82, 95% CI 1.13–2.79, p = 0.013). At both stages of treatment intensification, nonwhite groups had fewer HbA1c measurements than white groups. Limitations included variable quality and completeness of routinely recorded data and a lack of information on medication adherence.

Conclusions

In this large UK cohort, we found persuasive evidence that South Asian and black groups intensified to noninsulin combination therapy and insulin therapy more slowly than white groups and experienced greater therapeutic inertia following identification of uncontrolled HbA1c. Reasons for delays are multifactorial and may, in part, be related to poorer long-term monitoring of risk factors in nonwhite groups. Initiatives to improve timely and appropriate intensification of diabetes treatment are key to reducing disparities in downstream vascular outcomes in these populations.

National and regional prevalence of posttraumatic stress disorder in sub-Saharan Africa: A systematic review and meta-analysis

PLoS Medicine - Ve, 15/05/2020 - 23:00

by Lauren C. Ng, Anne Stevenson, Sreeja S. Kalapurakkel, Charlotte Hanlon, Soraya Seedat, Boniface Harerimana, Bonginkosi Chiliza, Karestan C. Koenen

Background

People living in sub-Saharan Africa (SSA) are disproportionately exposed to trauma and may be at increased risk for posttraumatic stress disorder (PTSD). However, a dearth of population-level representative data from SSA is a barrier to assessing PTSD. This manuscript sought to calculate pooled PTSD prevalence estimates from nationally and regionally representative surveys in SSA.

Methods and findings

The search was conducted in PubMed, Embase, PsycINFO, and PTSDpubs and was last run between October 18, 2019, and November 11, 2019. We included studies that were published in peer-reviewed journals; used probabilistic sampling methods and systematic PTSD assessments; and included ≥ 450 participants who were current residents of an SSA country, at least 50% of whom were aged between 15 and 65 years. The primary outcomes were point prevalence estimates of PTSD across all studies, and then within subgroups. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42016029441). Out of 2,825 unique articles reviewed, 25 studies including a total of 58,887 eligible participants (54% female) in 10 out of the 48 countries in SSA were identified. Most studies enrolled any adult aged 18 years or older. However, some studies only enrolled specific age brackets or persons as young as 15 years old. Six studies were national surveys, and 19 were regional.There were 4 key findings in the meta-analysis: (1) the overall pooled prevalence of probable PTSD was 22% (95% CI 13%–32%), while the current prevalence—defined as 1 week to 1 month—was 25% (95% CI 16%–36%); (2) prevalence estimates were highly variable, ranging from 0% (95% CI 0%–0%) to 74% (95% CI 72%–76%); (3) conflict-unexposed regions had a pooled prevalence of probable PTSD of 8% (95% CI 3%–15%), while conflict-exposed regions had a pooled prevalence of probable PTSD of 30% (95% CI 21%–40%; p < 0.001); and (4) there was no significant difference in the pooled prevalence of PTSD for men and women. The primary limitations of our methodology are our exclusion of the following study types: those published in languages other than English, French, and Portuguese; smaller studies; those that focused on key populations; those that reported only on continuous measures of PTSD symptoms; and unpublished or non–peer-reviewed studies.

Conclusions

In this study, PTSD symptoms consistent with a probable diagnosis were found to be common in SSA, especially in regions exposed to armed conflict. However, these studies only represent data from 10 of the 48 SSA countries, and only 6 studies provided national-level data. Given the enormous heterogeneity expected across the continent, and also within countries and regions, this review cannot speak to rates of PTSD in any regions not included in this review. Thus, substantial gaps in our knowledge of PTSD prevalence in SSA remain. More research on population-level prevalence is needed to determine the burden of trauma symptoms and PTSD in SSA and to identify acceptable and feasible approaches to address this burden given limited mental healthcare resources.

Wound-healing patch of blue-green algae mends skin quickly

New Scientist - Ve, 15/05/2020 - 21:00
A skin patch filled with living blue-green algae pumps oxygen into wounds to help them mend faster, and may help people with chronic wounds caused by diabetes

Wound-healing patch of blue-green algae mends skin quickly

New Scientist - Ve, 15/05/2020 - 21:00
A skin patch made of living blue-green algae speeds up wound healing in mice, and may help to treat chronic wounds in people with diabetes

We may have missed half the microplastics in the ocean

New Scientist - Ve, 15/05/2020 - 19:35
Collecting microplastics on the ocean’s surface with three kinds of net has revealed far more stringy fibres of plastic than previous studies found

We may have missed half the microplastics in the ocean

New Scientist - Ve, 15/05/2020 - 19:35
Collecting microplastics on the ocean’s surface with three kinds of net has revealed far more stringy fibres of plastic than previous studies found
Condividi contenuti