Background. Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence. Methods. Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken. Results. We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14–.45; I² = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified. Conclusions. Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection.

The prevalence of diabetes, heart disease, and stroke multimorbidity (co-occurrence of two or three of these conditions) has increased rapidly. Little is known about how the three conditions progress from one to another sequentially through the life course. We aimed to delineate this progression in middle-aged women and to determine the roles of common risk factors in the accumulation of diabetes, heart disease, and stroke multimorbidity. We used data from 13,714 women aged 45–50 years without a history of any of the three conditions. They were participants in the Australian Longitudinal Study on Women's Health (ALSWH), enrolled in 1996, and surveyed approximately every 3 years to 2016. We characterized the longitudinal progression of the three conditions and multimorbidity. We estimated the accumulation of multimorbidity over 20 years of follow-up and investigated their association with both baseline and time-varying predictors (sociodemographic factors, lifestyle factors, and other chronic conditions). Over 20 years, 2,511 (18.3%) of the women progressed to at least one condition, of whom 1,420 (56.6%) had diabetes, 1,277 (50.9%) had heart disease, and 308 (12.3%) had stroke; 423 (16.8%) had two or three of these conditions. Over a 3-year period, the age-adjusted odds of two or more conditions was approximately twice that of developing one new condition compared to women who did not develop any new conditions. For example, the odds for developing one new condition between Surveys 7 and 8 were 2.29 (95% confidence interval [CI], 1.93–2.72), whereas the odds for developing two or more conditions was 6.51 (95% CI, 3.95–10.75). The onset of stroke was more strongly associated with the progression to the other conditions (i.e., 23.4% [95% CI, 16.3%–32.2%] of women after first onset of stroke progressed to other conditions, whereas the percentages for diabetes and heart disease were 9.9% [95% CI, 7.9%–12.4%] and 11.4% [95% CI, 9.1%–14.4%], respectively). Being separated, divorced, or widowed; being born outside Australia; having difficulty managing on their available income; being overweight or obese; having hypertension; being physically inactive; being a current smoker; and having prior chronic conditions (i.e., mental disorders, asthma, cancer, osteoporosis, and arthritis) were significantly associated with increased odds of accumulation of diabetes, heart disease, and stroke multimorbidity. The main limitations of this study were the use of self-reported data and the low number of events. Stroke was associated with increased risk of progression to diabetes or heart disease. Social inequality, obesity, hypertension, physical inactivity, smoking, or having other chronic conditions were also significantly associated with increased odds of accumulating multimorbidity. Our findings highlight the importance of awareness of the role of diabetes, heart disease, and stroke multimorbidity among middle-aged women for clinicians and health-promotion agencies.

To summarize global research trends and activities on multimorbidity; then to assess the knowledge gaps and to identify implications for knowledge exchange between high income countries (HICs) and low- and middle- income countries (LMICs). A comprehensive search was conducted to identify research publications on multimorbidity in the Web of ScienceTM, as well as diabetes, depression, hypertension, and Chronic Obstructive Pulmonary Disease (COPD). The time frame for the search was from 1900 to June, 2016. Information (such as publication date, subject category, author, country of origin, title, abstract, and keywords) were extracted and the full texts were obtained for the co-citation analysis. Data were linked with the life expectancy at birth (years) and Gross National Income (GNI). Co-citation and hierarchal clustering analysis was used to map the trends and research networks with CiteSpace II (JAVA freeware, copyright Chaomei Chen, http://cluster.cis.drexel.edu/~cchen/citespace/). We identified 2864 relevant publications as at June 2016, with the first paper on this topic indexed in 1974 from Germany, but 80% were published after 2010. Further analysis yielded two knowledge gaps: (1) compared with single conditions (diabetes, hypertension, depression, and COPD), there is a mismatch between the high prevalence of multimorbidity and its research outputs (ratio of articles on multimorbidity vs other four single conditions is 1:13-150); (2) although a total of 76 countries have contributed to this research area, only 5% of research originated from LMICs where 73% of non-communicable disease (NCD) related deaths had occurred. Additional analysis showed the median year of first publication occurred 15 years later in the LMICs compared with HICs (2010 vs 1995); and longer life expectancy was associated with exponentially higher publication outputs (Pearson correlation coefficient r = 0.95) at the global level. The life expectancy at the median year (1994) of first publication was 66.1, with the gap between LMICs and HICs 7.9 (68.4 vs 76.3). This study confirms substantial knowledge gaps in the research agenda on multimorbidity, with input urgently needed to move us forward worldwide, especially for and in LMICs. There is the possibility that LMICs can learn from and collaborate with HICs in this area.

Many physical, psychological, and cognitive disorders are highly clustered among populations with low socioeconomic status. However, the extent to which socioeconomic status is associated with different combinations of these disorders is unclear, particularly outside high-income countries. We aimed to evaluate these associations in 33 countries including high-income countries, upper-middle-income countries, and one lower-middle-income country. This cross-sectional multi-region study pooled individual-level data from seven studies on ageing between 2017 and 2020. Education and total household wealth were used to measure socioeconomic status. Physical disorder was defined as having one or more of the self-reported chronic conditions. Psychological and cognitive disorders were measured by study-specific instruments. The outcome included eight categories: no disorders, physical disorder, psychological disorder, cognitive disorder, and their four combinations. Multivariable-adjusted logistic regression models were used to estimate odds ratios (ORs) and 95% CIs for the associations of socioeconomic status with these outcomes separately for high-income countries, upper-middle-income countries, and the lower-middle-income country. Among 167 376 individuals aged 45 years and older, the prevalence of multimorbidity was 24·5% in high-income countries, 33·9% in upper-middle-income countries, and 8·1% in the lower-middle-income country (India). Lower levels of education, household wealth, and a combined socioeconomic status score were strongly associated with physical, psychological, and cognitive multimorbidity in high-income countries and upper-middle-income countries, with ORs (low vs high socioeconomic status) for physical-psychological-cognitive multimorbidity of 12·36 (95% CI 10·29-14·85; p<0·0001) in high-income countries and of 23·84 (18·85-30·14; p<0·0001) in upper-middle-income countries. The associations in the lower-middle-income country were mixed. Participants with both a low level of education and low household wealth had the highest odds of multimorbidity (eg, OR for physical-psychological-cognitive multimorbidity 21·21 [15·95-28·19; p<0·0001] in high-income countries, 37·07 [25·66-53·56; p<0·0001] in upper-middle-income countries, and 54·96 [7·66-394·38; p<0·0001] in the lower-middle-income country). In study populations from high-income countries, upper-middle-income countries, and the lower-middle-income country, the odds of multimorbidity, which included physical, psychological, and cognitive disorders, were more than ten times greater in individuals with low socioeconomic status. Equity-oriented policies and programmes that reduce social inequalities in multimorbidity are urgently needed to achieve Sustainable Development Goals. Zhejiang University, Fundamental Research Funds for the Central Universities, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Wellcome Trust, Medical Research Council, National Institute on Aging, and Academy of Finland. For the Chinese translation of the abstract see Supplementary Materials section.

STUDY QUESTION: Is age at natural menopause (ANM) associated with the development of multiple chronic conditions (multimorbidity) in postmenopausal life? SUMMARY ANSWER: Women with premature menopause experience increased odds of developing individual chronic conditions and multimorbidity. WHAT IS KNOWN ALREADY: ANM is considered as a marker of age-related morbidity and mortality in postmenopausal life. Multimorbidity affects more than 60% of older women and has been recognized as the most common ‘chronic condition’. Few studies have examined the association between ANM and the development of multimorbidity. STUDY DESIGN, SIZE, DURATION: A prospective national cohort study of 11 258 Australian women, aged 45–50 years in 1996. Women were followed from 1996 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information about ANM and 11 chronic conditions (diabetes, hypertension, heart disease, stroke, arthritis, osteoporosis, asthma, chronic obstructive pulmonary disease, depression, anxiety and breast cancer) were estimated approximately every 3 years. Multimorbidity is defined as 2 or more of these 11 conditions. Generalized estimating equations were used to link the categorical ANM with individual chronic conditions and multimorbidity. MAIN RESULTS AND THE ROLE OF CHANCE: Among 5107 women reporting ANM, 2.3% experienced premature menopause (≤40 years) and 55.1% developed multimorbidity. Compared with women who experienced menopause at age 50–51 years, women with premature menopause had twice the odds of experiencing multimorbidity by age 60 (OR = 1.98, 95% CI 1.31 to 2.98) and three times the odds of developing multimorbidity in their 60s (OR = 3.03, 95% CI 1.62 to 5.64). Women with premature menopause also experienced higher incidence of most individual chronic conditions. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study was the use of self-reported data, but with repeated assessments from prospective study design and the validity of most of the chronic conditions from hospital data, the potential for non-differential misclassification is minimized. WIDE IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study to assess the association of premature menopause and development of multimorbidity in a larger national cohort of mid-aged women. Health professionals should consider comprehensive screening and assessment of risk factors for multimorbidity when treating women who experienced premature menopause. STUDY FUNDING/COMPETING INTEREST(S): The Australian Longitudinal Study on Women’s Health was supported by the Australian Government Department of Health. X.X. is funded by an International Postgraduate Research Scholarship from the Australian government and a UQ Centennial Scholarship from The University of Queensland. G.D.M. is supported by the National Health and Medical Research Council Principal Research Fellowship (APP1121844). None of the authors has any conflicts of interest to declare.