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This review identifies the emerging evidence to support policy for the management of people with multimorbidity and common comorbidities in primary care and community settings. There are remaining uncertainties about the effectiveness of interventions for people with multimorbidity in general due to the relatively small number of RCTs conducted in this area to date, with mixed findings overall. It is possible that the findings may change with the inclusion of large ongoing well-organised trials in future updates. The results suggest an improvement in health outcomes if interventions can be targeted at risk factors such as depression, or specific functional difficulties in people with multimorbidity.

BackgroundMultimorbidity affects up to one quarter of primary care populations. It is associated with reduced quality of life, an increased risk of mental health difficulties and increased healthcare utilisation. Functional decline is defined as developing difficulties with activities of daily living and is independently associated with poorer health outcomes. The aim of this systematic review was to examine the association between multimorbidity and functional decline and to what extent multimorbidity predicts future functional decline.MethodsA systematic literature search (1990-2014) and narrative analysis was conducted. Inclusion criteria: Population; Community-dwelling adults (≥18 years), Risk; Multimorbidity defined as the presence of ≥2 chronic medical conditions in an individual, Primary outcome; Physical functional decline measured using a validated instrument, Study design; cross-sectional or cohort studies. The following databases were included: PubMed, EMBASE, CINAHL, the Cochrane Library and the International Research Community on Multimorbidity (IRCMo) publication list. Methodological quality assessment of included studies was conducted with a suitable risk of bias tool.ResultsA total of 37 studies were eligible for inclusion (28 cross-sectional studies and 9 cohort studies). The majority of cross-sectional studies (n = 24/28) demonstrated a consistent association between multimorbidity and functional decline. Twelve of these studies reported that increasing numbers of chronic condition counts were associated with worsening functional decline. Nine cohort studies included 14,133 study participants with follow-up periods ranging from one to six years. The majority (n = 5) found that multimorbidity predicted functional decline. Of the five studies that reported the impact of increasing numbers of conditions, all reported greater functional decline with increasing numbers of conditions. One study examined disease severity and found that this also predicted greater functional decline. Overall, cohort studies were of good methodological quality but were mixed in terms of participants, multimorbidity definitions, follow-up duration, and outcome measures.ConclusionsThe available evidence indicates that multimorbidity predicts future functional decline, with greater decline in patients with higher numbers of conditions and greater disease severity. This review highlights the importance of considering physical functioning when designing interventions and systems of care for patients with multimorbidity, particularly for patients with higher numbers of conditions and greater disease severity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-015-0355-9) contains supplementary material, which is available to authorized users.

Background-Pulmonary arterial hypertension (PAH) is a hyperproliferative vascular disorder observed predominantly in women. Estrogen is a potent mitogen in human pulmonary artery smooth muscle cells and contributes to PAH in vivo; however, the mechanisms attributed to this causation remain obscure. Curiously, heightened expression of the estrogenmetabolizing enzyme cytochrome P450 1B1 (CYP1B1) is reported in idiopathic PAH and murine models of PAH. Methods and Results-Here, we investigated the putative pathogenic role of CYP1B1 in PAH. Quantitative reverse transcriptionpolymerase chain reaction, immunoblotting, and in situ analysis revealed that pulmonary CYP1B1 is increased in hypoxic PAH, hypoxicϩSU5416 PAH, and human PAH and is highly expressed within the pulmonary vascular wall. PAH was assessed in mice via measurement of right ventricular hypertrophy, pulmonary vascular remodeling, and right ventricular systolic pressure. Hypoxic PAH was attenuated in CYP1B1 Ϫ/Ϫ mice, and the potent CYP1B1 inhibitor 2,3Ј,4,5Ј-tetramethoxystilbene (TMS; 3 mg ⅐ kg Ϫ1 ⅐ d

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Clinical questionWhat are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice.Current practiceCurrent guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing.RecommendationThe guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old).How this guideline was createdA guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach.The evidenceThe systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years’ follow-up.Understanding the recommendationThe panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC (https://app.magicapp.org/) to support shared decisions and adaptation of this guideline.

One standout feature of human language is our ability to reference external objects and events with socially learned symbols, or words. Exploring the phylogenetic origins of this capacity is therefore key to a comprehensive understanding of the evolution of language. While non-human primates can produce vocalizations that refer to external objects in the environment, it is generally accepted that their acoustic structure is fixed and a product of arousal states. Indeed, it has been argued that the apparent lack of flexible control over the structure of referential vocalizations represents a key discontinuity with language. Here, we demonstrate vocal learning in the acoustic structure of referential food grunts in captive chimpanzees. We found that, following the integration of two groups of adult chimpanzees, the acoustic structure of referential food grunts produced for a specific food converged over 3 years. Acoustic convergence arose independently of preference for the food, and social network analyses indicated this only occurred after strong affiliative relationships were established between the original subgroups. We argue that these data represent the first evidence of non-human animals actively modifying and socially learning the structure of a meaningful referential vocalization from conspecifics. Our findings indicate that primate referential call structure is not simply determined by arousal and that the socially learned nature of referential words in humans likely has ancient evolutionary origins.

PURPOSE We aimed to develop a consensus-based set of core outcomes specifically for studies in multimorbidity. METHODSWe undertook a consensus study following the COS-STAR (Core Outcome Set-STAndards for Reporting) guidelines for the design and reporting of core outcome sets. A Delphi panel of experts completed a web-based survey with 2 rounds. Panelists were presented with a range of outcomes that had been identified in previous workshops and a related systematic review. They indicated their level of agreement on whether each outcome should be included in the core set using a 5-point Likert scale, and outcomes reaching a prespecified consensus level were included. RESULTSOf 30 individuals invited to be panelists, 26 from 13 countries agreed. All 26 completed both rounds of the survey. The Delphi panel reached consensus on 17 outcomes for inclusion in a core outcome set for multimorbidity (COSmm). The highest-ranked outcomes were health-related quality of life, mental health outcomes, and mortality. Other outcomes were grouped into overarching themes of patient-reported impacts and behaviors (treatment burden, self-rated health, self-management behavior, self-efficacy, adherence); physical activity and function (activities of daily living, physical function, physical activity); consultation related (communication, shared decision making, prioritization); and health systems (health care use, costs, quality of health care). CONCLUSIONSThis consensus study involved a wide range of international experts who identified a large number of outcomes for multimorbidity intervention studies. Our results suggest that quality of life, mental health outcomes, and mortality should be regarded as essential core outcomes. Researchers should, however, also consider the full range of outcomes when designing studies to capture important domains in multimorbidity depending on individual study aims and interventions.