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Randomized, Controlled Trial of an Advance Care Planning Video Decision Support Tool for Patients With Advanced Heart Failure.

Background: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. Methods: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention. Results: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). Conclusions: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120.

Circulation · randomised controlled trial · 88 citationsread the source →

Interventions to reduce behavioral problems in children with cerebral palsy: an RCT.

Objective: To test Stepping Stones Triple P (SSTP) and Acceptance and Commitment Therapy (ACT) in a trial targeting behavioral problems in children with cerebral palsy (CP). Methods: Sixty-seven parents (97.0% mothers; mean age 38.7 ± 7.1 years) of children (64.2% boys; mean age 5.3 ± 3.0 years) with CP (Gross Motor Function Classification System = 15, 22%; II = 18, 27%; III =12, 18%; IV = 18, 27%; V = 4, 6%) participated and were randomly assigned to SSTP, SSTP + ACT, or waitlist. Primary outcomes were behavioral and emotional problems (Eyberg Child Behavior Inventory [ECBI], Strengths and Difficulties Questionnaire [SDQ]) and parenting style (Parenting Scale [PS]) at postintervention and 6-month follow-up. Results: SSTP with ACT was associated with decreased behavioral problems (ECBI Intensity mean difference [MD] = 24.12, confidence interval [CI] 10.22 to 38.03, P = .003; ECBI problem MD = 8.30, CI 4.63 to 11.97, P < .0001) including hyperactivity (SDQ MD = 1.66, CI 0.55 to 2.77, P = .004), as well as decreased parental overreactivity (PS MD = 0.60, CI 0.16 to 1.04, P = .008) and verbosity (PS MD = 0.68, CI 0.17 to 1.20, P = .01). SSTP alone was associated with decreased behavioral problems (ECBI problems MD = 6.04, CI 2.20 to 9.89, P = .003) and emotional symptoms (SDQ MD = 1.33, CI 0.45 to 2.21, P = .004). Decreases in behavioral and emotional problems were maintained at follow-up. Conclusions: SSTP is an effective intervention for behavioral problems in children with CP. ACT delivers additive benefits.

Pediatrics · randomised controlled trial · 53 citationsread the source →

Heart rate variability

IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. 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American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →

Interventions to improve return to work in depressed people.

Background: Work disability such as sickness absence is common in people with depression. Objectives: To evaluate the effectiveness of interventions aimed at reducing work disability in employees with depressive disorders. Search methods: We searched CENTRAL (The Cochrane Library), MEDLINE, Embase, CINAHL, and PsycINFO until April 4th 2020. Selection criteria: We included randomised controlled trials (RCTs) and cluster-RCTs of work-directed and clinical interventions for depressed people that included days of sickness absence or being off work as an outcome. We also analysed the effects on depression and work functioning. Data collection and analysis: Two review authors independently extracted the data and rated the certainty of the evidence using GRADE. We used standardised mean differences (SMDs) or risk ratios (RR) with 95% confidence intervals (CI) to pool study results in studies we judged to be sufficiently similar.  MAIN RESULTS: In this update, we added 23 new studies. In total, we included 45 studies with 88 study arms, involving 12,109 participants with either a major depressive disorder or a high level of depressive symptoms. Risk of bias The most common types of bias risk were detection bias (27 studies) and attrition bias (22 studies), both for the outcome of sickness absence. Work-directed interventions Work-directed interventions combined with clinical interventions A combination of a work-directed intervention and a clinical intervention probably reduces days of sickness absence within the first year of follow-up (SMD -0.25, 95% CI -0.38 to -0.12; 9 studies; moderate-certainty evidence). This translates back to 0.5 fewer (95% CI -0.7 to -0.2) sick leave days in the past two weeks or 25 fewer days during one year (95% CI -37.5 to -11.8). The intervention does not lead to fewer persons being off work beyond one year follow-up (RR 0.96, 95% CI 0.85 to 1.09; 2 studies, high-certainty evidence). The intervention may reduce depressive symptoms (SMD -0.25, 95% CI -0.49 to -0.01; 8 studies, low-certainty evidence) and probably has a small effect on work functioning (SMD -0.19, 95% CI -0.42 to 0.06; 5 studies, moderate-certainty evidence) within the first year of follow-up.  Stand alone work-directed interventions A specific work-directed intervention alone may increase the number of sickness absence days compared with work-directed care as usual (SMD 0.39, 95% CI 0.04 to 0.74; 2 studies, low-certainty evidence) but probably does not lead to more people being off work within the first year of follow-up (RR 0.93, 95% CI 0.77 to 1.11; 1 study, moderate-certainty evidence) or beyond (RR 1.00, 95% CI 0.82 to 1.22; 2 studies, moderate-certainty evidence). There is probably no effect on depressive symptoms (SMD -0.10, 95% -0.30 CI to 0.10; 4 studies, moderate-certainty evidence) within the first year of follow-up and there may be no effect on depressive symptoms beyond that time (SMD 0.18, 95% CI -0.13 to 0.49; 1 study, low-certainty evidence). The intervention may also not lead to better work functioning (SMD -0.32, 95% CI -0.90 to 0.26; 1 study, low-certainty evidence) within the first year of follow-up.   Psychological interventions A psychological intervention, either face-to-face, or an E-mental health intervention, with or without professional guidance, may reduce the number of sickness absence days, compared with care as usual (SMD -0.15, 95% CI -0.28 to -0.03; 9 studies, low-certainty evidence). It may also reduce depressive symptoms (SMD -0.30, 95% CI -0.45 to -0.15, 8 studies, low-certainty evidence). We are uncertain whether these psychological interventions improve work ability (SMD -0.15 95% CI -0.46 to 0.57; 1 study; very low-certainty evidence). Psychological intervention combined with antidepressant medication Two studies compared the effect of a psychological intervention combined with antidepressants to antidepressants alone. One study combined psychodynamic therapy with tricyclic antidepressant (TCA) medication and another combined telephone-administered cognitive behavioural therapy (CBT) with a selective serotonin reuptake inhibitor (SSRI). We are uncertain if this intervention reduces the number of sickness absence days (SMD -0.38, 95% CI -0.99 to 0.24; 2 studies, very low-certainty evidence) but found that there may be no effect on depressive symptoms (SMD -0.19, 95% CI -0.50 to 0.12; 2 studies, low-certainty evidence). Antidepressant medication only Three studies compared the effectiveness of SSRI to selective norepinephrine reuptake inhibitor (SNRI) medication on reducing sickness absence and yielded highly inconsistent results. Improved care Overall, interventions to improve care did not lead to fewer days of sickness absence, compared to care as usual (SMD -0.05, 95% CI -0.16 to 0.06; 7 studies, moderate-certainty evidence). However, in studies with a low risk of bias, the intervention probably leads to fewer days of sickness absence in the first year of follow-up (SMD -0.20, 95% CI -0.35 to -0.05; 2 studies; moderate-certainty evidence). Improved care probably leads to fewer depressive symptoms (SMD -0.21, 95% CI -0.35 to -0.07; 7 studies, moderate-certainty evidence) but may possibly lead to a decrease in work-functioning (SMD 0.5, 95% CI 0.34 to 0.66; 1 study; moderate-certainty evidence). Exercise Supervised strength exercise may reduce sickness absence, compared to relaxation (SMD -1.11; 95% CI -1.68 to -0.54; one study, low-certainty evidence). However, aerobic exercise probably is not more effective than relaxation or stretching (SMD -0.06; 95% CI -0.36 to 0.24; 2 studies, moderate-certainty evidence). Both studies found no differences between the two conditions in depressive symptoms. Authors' conclusions: A combination of a work-directed intervention and a clinical intervention probably reduces the number of sickness absence days, but at the end of one year or longer follow-up, this does not lead to more people in the intervention group being at work. The intervention may also reduce depressive symptoms and probably increases work functioning more than care as usual. Specific work-directed interventions may not be more effective than usual work-directed care alone. Psychological interventions may reduce the number of sickness absence days, compared with care as usual. Interventions to improve clinical care probably lead to lower sickness absence and lower levels of depression, compared with care as usual. There was no evidence of a difference in effect on sickness absence of one antidepressant medication compared to another. Further research is needed to assess which combination of work-directed and clinical interventions works best.

The Cochrane database of systematic reviews · meta-analysis · 158 citationsread the source →

The Impact of Family Environment on Language Development of Children With Cochlear Implants: A Systematic Review and Meta-Analysis.

Objectives: The authors conducted a systematic review of the literature and meta-analyses to assess the influence of family environment on language development in children with cochlear implants. Design: The Pubmed, excerpta medica dataBASE (EMBASE), Education Research Information Center, cumulative index to nursing and allied health literature (CINAHL), Healthcare Literature Information Network, PubPsych, and Social SciSearch databases were searched. The search strategy included terms describing family environment, child characteristics, and language development. Studies were included that (a) assessed distal family variables (such as parental income level, parental education, family size, and parental stress) with child language outcomes, and/or more proximal correlates that directly affect the child (such as family engagement and participation in intervention, parenting style, and more specifically, the quantity and quality of parental linguistic input) on child language; (b) included children implanted before the age of 5 years; (c) measured child language before the age of 21 years with standardized instruments; (d) were published between 1995 and February 2018; and (e) were published as peer-reviewed articles. The methodological quality was assessed with an adaptation of a previously validated checklist. Meta-analyses were conducted assuming a random-effects model. Results: A total of 22 study populations reported in 27 publications were included. Methodological quality was highly variable. Ten studies had a longitudinal design. Three meta-analyses on the correlations between family variables and child language development could be performed. A strong effect of the quality and quantity of parental linguistic input in the first 4½ years postimplantation on the child's language was found, r = 0.564, p ≤ 0.001, 95% confidence interval (CI) = 0.449 to 0.660, accounting for 31.7% of the variance in child language outcomes. Results demonstrated high homogeneity, Q(3) = 1.823, p = 0.61, I = 0. Higher-level facilitative language techniques, such as parental expansions of the child's utterances or the use of open-ended questions, predicted child language skills. Risk of publication bias was not detected. The results on the impact of family involvement/participation in intervention on child language development were more heterogeneous. The meta-analysis included mainly cross-sectional studies and identified low to moderate benefits, r = 0.380, p ≤ 0.052, 95% CI = -0.004 to 0.667, that almost attained significance level. Socioeconomic status, mainly operationalized by parental level of education, showed a positive correlation with child language development in most studies. The meta-analysis confirmed an overall low and nonsignificant average correlation coefficient, r = 0.117, p = 0.262, 95% CI = -0.087 to 0.312. A limitation of the study was the lack of some potentially relevant variables, such as multilingualism or family screen time. Conclusions: These data support the hypothesis that parental linguistic input during the first years after cochlear implantation strongly predicts later child language outcomes. Effects of parental involvement in intervention and parental education are comparatively weaker and more heterogeneous. These findings underscore the need for early-intervention programs for children with cochlear implants focusing on providing support to parents for them to increase their children's exposure to high-quality conversation.

Ear and hearing · meta-analysis · 59 citationsread the source →

The association between social support and physical activity in older adults: a systematic review.

Background: The promotion of active and healthy ageing is becoming increasingly important as the population ages. Physical activity (PA) significantly reduces all-cause mortality and contributes to the prevention of many chronic illnesses. However, the proportion of people globally who are active enough to gain these health benefits is low and decreases with age. Social support (SS) is a social determinant of health that may improve PA in older adults, but the association has not been systematically reviewed. This review had three aims: 1) Systematically review and summarise studies examining the association between SS, or loneliness, and PA in older adults; 2) clarify if specific types of SS are positively associated with PA; and 3) investigate whether the association between SS and PA differs between PA domains. Methods: Quantitative studies examining a relationship between SS, or loneliness, and PA levels in healthy, older adults over 60 were identified using MEDLINE, PSYCInfo, SportDiscus, CINAHL and PubMed, and through reference lists of included studies. Quality of these studies was rated. Results: This review included 27 papers, of which 22 were cross sectional studies, three were prospective/longitudinal and two were intervention studies. Overall, the study quality was moderate. Four articles examined the relation of PA with general SS, 17 with SS specific to PA (SSPA), and six with loneliness. The results suggest that there is a positive association between SSPA and PA levels in older adults, especially when it comes from family members. No clear associations were identified between general SS, SSPA from friends, or loneliness and PA levels. When measured separately, leisure time PA (LTPA) was associated with SS in a greater percentage of studies than when a number of PA domains were measured together. Conclusions: The evidence surrounding the relationship between SS, or loneliness, and PA in older adults suggests that people with greater SS for PA are more likely to do LTPA, especially when the SS comes from family members. However, high variability in measurement methods used to assess both SS and PA in included studies made it difficult to compare studies.

The international journal of behavioral nutrition and physical activity · systematic review · 472 citationsread the source →

Ulipristal Acetate for Treatment of Premenstrual Dysphoric Disorder: A Proof-of-Concept Randomized Controlled Trial.

Objective: Premenstrual dysphoric disorder (PMDD) is a common mood disorder, characterized by distressing affective, behavioral, and somatic symptoms in the late luteal phase of the menstrual cycle. The authors investigated continuous treatment with a selective progesterone receptor modulator, ulipristal acetate (UPA), as a potential treatment for PMDD. Methods: The authors conducted an investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial in which women with PMDD (N=95) were treated with either 5 mg/day of UPA or placebo during three 28-day treatment cycles. The primary outcome was the change in premenstrual total score on the Daily Record of Severity of Problems (DRSP) from baseline to end of treatment. DRSP scores were captured by daily ratings using a smartphone application and were analyzed with linear mixed models for repeated measures. Results: The mean improvement in DRSP score after 3 months was 41% (SD=18) in the UPA group, compared with 22% (SD=27) in the placebo group (mean difference -18%; 95% CI=-29, -8). Treatment effects were also noted for the DRSP depressive symptom subscale (42% [SD=22] compared with 22% [SD=32]) and the DRSP anger/irritability subscale (47% [SD=21] compared with 23% [SD=35]), but not for the DRSP physical symptom subscale. Remission based on DRSP score was attained by 20 women in the UPA group (50.0%) and eight women in the placebo group (21.1%) (a statistically significant difference). Conclusions: If these results are replicated, UPA could be a useful treatment for PMDD, particularly for the psychological symptoms associated with the disorder.

The American journal of psychiatry · randomised controlled trial · 56 citationsread the source →

Effects of a parenting intervention to address maternal psychological wellbeing and child development and growth in rural Uganda: a community-based, cluster randomised trial.

Background: Parenting interventions have been implemented to improve the compromised developmental potential among 39% of children younger than 5 years living in low-income and middle-income countries. Maternal wellbeing is important for child development, especially in children younger than 3 years who are vulnerable and dependent on their mothers for nutrition and stimulation. We assessed an integrated, community-based parenting intervention that targeted both child development and maternal wellbeing in rural Uganda. Methods: In this community-based, cluster randomised trial, we assessed the effectiveness of a manualised, parenting intervention in Lira, Uganda. We selected and randomly assigned 12 parishes (1:1) to either parenting intervention or control (inclusion on a waitlist with a brief message on nutrition) groups using a computer-generated list of random numbers. Within each parish, we selected two to three eligible communities that had a parish office or a primary school in which a preschool could be established, more than 75 households with children younger than 6 years, and at least 15 socially disadvantaged families (ie, maternal education of primary school level or lower) with at least one child younger than 36 months. Participants within communities were mother-child dyads, where the child was 12-36 months of age at enrollment, and the mother had low maternal education. In the parenting intervention group, participants attended 12 fortnightly peer-led group sessions focusing on child care and maternal wellbeing. The primary outcomes were cognitive and receptive language development, as measured with the Bayley Scales of Infant Development, 3rd edn. Secondary outcomes included self-reported maternal depressive symptoms, using the Center for Epidemiologic Studies Depression Scale, and child growth. Theoretically-relevant parenting practices, including the Home Observation for Measurement of the Environment inventory, and mother-care variables, such as perceived spousal support, were also assessed as potential mediators. Baseline assessments were done in January, 2013, and endline assessments were done in November, 2013, 3 months after completion of the programme. Ethics approval was received from Mbarara and McGill universities. This trial is registered with ClinicalTrials.gov, NCT01906606. Findings: Between December, 2012, and January, 2013, 13 communities (194 dyads) were randomly assigned to receive intervention, and 12 communities (154 dyads) were assigned to a waitlist control. 319 dyads completed baseline measures (171 in the intervention group and 148 in the control group), and 291 dyads completed endline measures (160 in the intervention group and 131 in the control group). At endline, children in the intervention group had significantly higher cognitive scores (58·90 vs 55·65, effect size 0·36, 95% CI 0·12-0·59) and receptive language scores (23·86 vs 22·40, 0·27, 0·03-0·50) than did children in the control group. Mothers in the intervention group reported significantly fewer depressive symptoms (15·36 vs 18·61, -0·391, 95% CI -0·62 to -0·16) than did mothers in the control group. However, no differences were found in child growth between groups. Interpretation: The 12 session integrated parenting intervention delivered by non-professional community members improved child development and maternal wellbeing in rural Uganda. Because this intervention was largely managed and implemented by a local organisation, using local community members and minimal resources, such a programme has the potential to be replicated and scaled up in other low-resource, village-based settings. Funding: Plan Uganda via Plan Finland (Ministry of Foreign Affairs) and Plan Australia (Australian Aid).

The Lancet. Global health · randomised controlled trial · 208 citationsread the source →

Telephone-Delivered Cognitive Behavioral Therapy and Telephone-Delivered Nondirective Supportive Therapy for Rural Older Adults With Generalized Anxiety Disorder

IMPORTANCE: Generalized anxiety disorder (GAD) is common in older adults; however, access to treatment may be limited, particularly in rural areas. OBJECTIVE: To examine the effects of telephone-delivered cognitive behavioral therapy (CBT) compared with telephone-delivered nondirective supportive therapy (NST) in rural older adults with GAD. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial in the participants' homes of 141 adults aged 60 years and older with a principal or coprincipal diagnosis of GAD who were recruited between January 27, 2011, and October 22, 2013. INTERVENTIONS: Telephone-delivered CBT consisted of as many as 11 sessions (9 were required) focused on recognition of anxiety symptoms, relaxation, cognitive restructuring, the use of coping statements, problem solving, worry control, behavioral activation, exposure therapy, and relapse prevention, with optional chapters on sleep and pain. Telephone-delivered NST consisted of 10 sessions focused on providing a supportive atmosphere in which participants could share and discuss their feelings and did not provide any direct suggestions for coping. MAIN OUTCOMES AND MEASURES: Primary outcomes included interviewer-rated anxiety severity (Hamilton Anxiety Rating Scale) and self-reported worry severity (Penn State Worry Questionnaire-Abbreviated) measured at baseline, 2 months' follow-up, and 4 months' follow-up. Mood-specific secondary outcomes included self-reported GAD symptoms (GAD Scale 7 Item) measured at baseline and 4 months' follow-up and depressive symptoms (Beck Depression Inventory) measured at baseline, 2 months' follow-up, and 4 months' follow-up. Among the 141 participants, 70 were randomized to receive CBT and 71 to receive NST. RESULTS: At 4 months' follow-up, there was a significantly greater decline in worry severity among participants in the telephone-delivered CBT group (difference in improvement, -4.07; 95% CI, -6.26 to -1.87; P = .004) but no significant differences in general anxiety symptoms (difference in improvement, -1.52; 95% CI, -4.07 to 1.03; P = .24). At 4 months' follow-up, there was a significantly greater decline in GAD symptoms (difference in improvement, -2.36; 95% CI, -4.00 to -0.72; P = .005) and depressive symptoms (difference in improvement, -3.23; 95% CI, -5.97 to -0.50; P = .02) among participants in the telephone-delivered CBT group. CONCLUSIONS AND RELEVANCE: In this trial, telephone-delivered CBT was superior to telephone-delivered NST in reducing worry, GAD symptoms, and depressive symptoms in older adults with GAD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01259596.

JAMA Psychiatry · randomised controlled trial · 145 citationsread the source →

Omega-3 fatty acid supplementation in patients with recurrent self-harm. Single-centre double-blind randomised controlled trial.

Background: Trials have demonstrated benefits of long-chain omega-3 essential fatty acid (n-3 EFA) supplementation in a variety of psychiatric disorders. Aims: To assess the efficacy of n-3 EFAs in improving psychological well-being in patients with recurrent self-harm. Method: Patients (n=49) presenting after an act of repeated self-harm were randomised to receive 1.2 g eicosapentaenoic acid plus 0.9 g decosahexaenoic acid (n=22) or placebo (n=27) for 12 weeks in addition to standard psychiatric care. Six psychological domains were measured at baseline and end point. Results: At 12 weeks, the n-3 EFA group had significantly greater improvements in scores for depression, suicidality and daily stresses. Scores for impulsivity, aggression and hostility did not differ. Conclusions: Supplementation achieved substantial reductions in surrogate markers of suicidal behaviour and improvements in well-being. Larger studies are warranted to determine if insufficient dietary intake of n-3 EFAs is a reversible risk factor for self-harm.

The British journal of psychiatry : the journal of mental science · randomised controlled trial · 105 citationsread the source →

Risk Factors, Imaging Findings, and Sex Differences in Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is increasingly being recognized. However, data supporting diagnosis and management are scarce. We analyze a contemporary and comprehensive SCAD registry to advance the understanding of SCAD risk factors, angiographic appearance, and gender differences. This is a retrospective analysis of a prospectively populated database of SCAD patients seen at the Massachusetts General Hospital (MGH) between June 2013 and October 2017. Core laboratory analysis of both coronary angiograms and computerized tomographic (CT) angiography of the extracoronary vessels was performed. Of the 113 patients, 87% were female and mean age was 47 ± 10 years. Traditional cardiovascular risk factors including hypertension, hyperlipidemia, and smoking were present in 27%, 14%, and 22% of patients. Among females, 14%, 8%, and 9% had a history of gestational hypertension, pre-eclampsia, and gestational diabetes, respectively. Fifteen percent had used fertility treatment and 47% of postmenopausal women had used hormone replacement therapy. Angiography showed multivessel SCAD in 42%, severe coronary artery tortuosity in 59%, and extracoronary vascular abnormalities in 100% of patients with complete CT angiographic imaging. Gender differences revealed a self-reported depression and anxiety prevalence of 20% and 32%, respectively, in women compared with 0% in men. Type 1 SCAD was more commonly diagnosed in men than women (71% vs 29%, p <0.01). In conclusion, we highlight under-recognized features of SCAD including (1) relation with pregnancy complications and exposure to hormonal therapy; (2) diffuse, multivessel process in tortuous coronaries on a background of extracoronary arterial abnormalities; and (3) gender differences highlighting the role of mental health as well as potential underdiagnoses in men.

The American journal of cardiology · cohort or longitudinal · 74 citationsread the source →

Quality of life of Danish colorectal cancer patients with and without a stoma.

Goals of the work: As part of a psychosocial intervention study, we wanted to prospectively assess the quality of life of colorectal cancer patients who were given a stoma at the time of their initial operation for cancer or later and those whose initial stoma was removed. Materials and methods: A total of 249 colorectal cancer patients were recruited and responded to a questionnaire 3, 6, 12 and 24 months after the initial operation (26-35% had a stoma during follow-up). Main results: Although most of the differences between stoma and non-stoma patients failed to reach significance, 22 out of 27 variables indicated a poorer quality of life for those with a stoma. Patients who currently had a stoma had significantly higher levels of depression (p = 0.013), poorer social functioning (p = 0.0085) and more problems with body image (p = 0.0001), future perspectives (p = 0.0058), micturition (p = 0.018) and side effects from chemotherapy (p = 0.008), but fewer problems with constipation (p = 0.034) than non-stoma patients. Male patients with a stoma had more sexual problems than males without a stoma (p = 0.015). Among those with a current stoma, quality of life seemed poorer among those whose stoma was made during follow-up compared with those with an initial stoma. Conclusions: Trends suggested that having a stoma led to poorer scores in most aspects of quality of life and that having a stoma made some time after the initial operation was more distressing than having a stoma made during the primary cancer operation.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · cohort or longitudinal · 92 citationsread the source →

Estimated Reductions in Opioid Overdose Deaths With Sustainment of Public Health Interventions in 4 US States.

Importance: In 2021, more than 80 000 US residents died from an opioid overdose. Public health intervention initiatives, such as the Helping to End Addiction Long-term (HEALing) Communities Study (HCS), are being launched with the goal of reducing opioid-related overdose deaths (OODs). Objective: To estimate the change in the projected number of OODs under different scenarios of the duration of sustainment of interventions, compared with the status quo. Design, setting, and participants: This decision analytical model simulated the opioid epidemic in the 4 states participating in the HCS (ie, Kentucky, Massachusetts, New York, and Ohio) from 2020 to 2026. Participants were a simulated population transitioning from opioid misuse to opioid use disorder (OUD), overdose, treatment, and relapse. The model was calibrated using 2015 to 2020 data from the National Survey on Drug Use and Health, the US Centers for Disease Control and Prevention, and other sources for each state. The model accounts for reduced initiation of medications for OUD (MOUDs) and increased OODs during the COVID-19 pandemic. Exposure: Increasing MOUD initiation by 2- or 5-fold, improving MOUD retention to the rates achieved in clinical trial settings, increasing naloxone distribution efforts, and furthering safe opioid prescribing. An initial 2-year duration of interventions was simulated, with potential sustainment for up to 3 additional years. Main outcomes and measures: Projected reduction in number of OODs under different combinations and durations of sustainment of interventions. Results: Compared with the status quo, the estimated annual reduction in OODs at the end of the second year of interventions was 13% to 17% in Kentucky, 17% to 27% in Massachusetts, 15% to 22% in New York, and 15% to 22% in Ohio. Sustaining all interventions for an additional 3 years was estimated to reduce the annual number of OODs at the end of the fifth year by 18% to 27% in Kentucky, 28% to 46% in Massachusetts, 22% to 34% in New York, and 25% to 41% in Ohio. The longer the interventions were sustained, the better the outcomes; however, these positive gains would be washed out if interventions were not sustained. Conclusions and relevance: In this decision analytical model study of the opioid epidemic in 4 US states, sustained implementation of interventions, including increased delivery of MOUDs and naloxone supply, was found to be needed to reduce OODs and prevent deaths from increasing again.

JAMA network open · 32 citationsread the source →

Interventions to prevent obesity in children aged 5 to 11 years old.

Background: Prevention of obesity in children is an international public health priority given the prevalence of the condition (and its significant impact on health, development and well-being). Interventions that aim to prevent obesity involve behavioural change strategies that promote healthy eating or 'activity' levels (physical activity, sedentary behaviour and/or sleep) or both, and work by reducing energy intake and/or increasing energy expenditure, respectively. There is uncertainty over which approaches are more effective and numerous new studies have been published over the last five years, since the previous version of this Cochrane review. Objectives: To assess the effects of interventions that aim to prevent obesity in children by modifying dietary intake or 'activity' levels, or a combination of both, on changes in BMI, zBMI score and serious adverse events. Search methods: We used standard, extensive Cochrane search methods. The latest search date was February 2023. Selection criteria: Randomised controlled trials in children (mean age 5 years and above but less than 12 years), comparing diet or 'activity' interventions (or both) to prevent obesity with no intervention, usual care, or with another eligible intervention, in any setting. Studies had to measure outcomes at a minimum of 12 weeks post baseline. We excluded interventions designed primarily to improve sporting performance. Data collection and analysis: We used standard Cochrane methods. Our outcomes were body mass index (BMI), zBMI score and serious adverse events, assessed at short- (12 weeks to < 9 months from baseline), medium- (9 months to < 15 months) and long-term (≥ 15 months) follow-up. We used GRADE to assess the certainty of the evidence for each outcome. Main results: This review includes 172 studies (189,707 participants); 149 studies (160,267 participants) were included in meta-analyses. One hundred forty-six studies were based in high-income countries. The main setting for intervention delivery was schools (111 studies), followed by the community (15 studies), the home (eight studies) and a clinical setting (seven studies); one intervention was conducted by telehealth and 31 studies were conducted in more than one setting. Eighty-six interventions were implemented for less than nine months; the shortest was conducted over one visit and the longest over four years. Non-industry funding was declared by 132 studies; 24 studies were funded in part or wholly by industry. Dietary interventions versus control Dietary interventions, compared with control, may have little to no effect on BMI at short-term follow-up (mean difference (MD) 0, 95% confidence interval (CI) -0.10 to 0.10; 5 studies, 2107 participants; low-certainty evidence) and at medium-term follow-up (MD -0.01, 95% CI -0.15 to 0.12; 9 studies, 6815 participants; low-certainty evidence) or zBMI at long-term follow-up (MD -0.05, 95% CI -0.10 to 0.01; 7 studies, 5285 participants; low-certainty evidence). Dietary interventions, compared with control, probably have little to no effect on BMI at long-term follow-up (MD -0.17, 95% CI -0.48 to 0.13; 2 studies, 945 participants; moderate-certainty evidence) and zBMI at short- or medium-term follow-up (MD -0.06, 95% CI -0.13 to 0.01; 8 studies, 3695 participants; MD -0.04, 95% CI -0.10 to 0.02; 9 studies, 7048 participants; moderate-certainty evidence). Five studies (1913 participants; very low-certainty evidence) reported data on serious adverse events: one reported serious adverse events (e.g. allergy, behavioural problems and abdominal discomfort) that may have occurred as a result of the intervention; four reported no effect. Activity interventions versus control Activity interventions, compared with control, may have little to no effect on BMI and zBMI at short-term or long-term follow-up (BMI short-term: MD -0.02, 95% CI -0.17 to 0.13; 14 studies, 4069 participants; zBMI short-term: MD -0.02, 95% CI -0.07 to 0.02; 6 studies, 3580 participants; low-certainty evidence; BMI long-term: MD -0.07, 95% CI -0.24 to 0.10; 8 studies, 8302 participants; zBMI long-term: MD -0.02, 95% CI -0.09 to 0.04; 6 studies, 6940 participants; low-certainty evidence). Activity interventions likely result in a slight reduction of BMI and zBMI at medium-term follow-up (BMI: MD -0.11, 95% CI -0.18 to -0.05; 16 studies, 21,286 participants; zBMI: MD -0.05, 95% CI -0.09 to -0.02; 13 studies, 20,600 participants; moderate-certainty evidence). Eleven studies (21,278 participants; low-certainty evidence) reported data on serious adverse events; one study reported two minor ankle sprains and one study reported the incident rate of adverse events (e.g. musculoskeletal injuries) that may have occurred as a result of the intervention; nine studies reported no effect. Dietary and activity interventions versus control Dietary and activity interventions, compared with control, may result in a slight reduction in BMI and zBMI at short-term follow-up (BMI: MD -0.11, 95% CI -0.21 to -0.01; 27 studies, 16,066 participants; zBMI: MD -0.03, 95% CI -0.06 to 0.00; 26 studies, 12,784 participants; low-certainty evidence) and likely result in a reduction of BMI and zBMI at medium-term follow-up (BMI: MD -0.11, 95% CI -0.21 to 0.00; 21 studies, 17,547 participants; zBMI: MD -0.05, 95% CI -0.07 to -0.02; 24 studies, 20,998 participants; moderate-certainty evidence). Dietary and activity interventions compared with control may result in little to no difference in BMI and zBMI at long-term follow-up (BMI: MD 0.03, 95% CI -0.11 to 0.16; 16 studies, 22,098 participants; zBMI: MD -0.02, 95% CI -0.06 to 0.01; 22 studies, 23,594 participants; low-certainty evidence). Nineteen studies (27,882 participants; low-certainty evidence) reported data on serious adverse events: four studies reported occurrence of serious adverse events (e.g. injuries, low levels of extreme dieting behaviour); 15 studies reported no effect. Heterogeneity was apparent in the results for all outcomes at the three follow-up times, which could not be explained by the main setting of the interventions (school, home, school and home, other), country income status (high-income versus non-high-income), participants' socioeconomic status (low versus mixed) and duration of the intervention. Most studies excluded children with a mental or physical disability. Authors' conclusions: The body of evidence in this review demonstrates that a range of school-based 'activity' interventions, alone or in combination with dietary interventions, may have a modest beneficial effect on obesity in childhood at short- and medium-term, but not at long-term follow-up. Dietary interventions alone may result in little to no difference. Limited evidence of low quality was identified on the effect of dietary and/or activity interventions on severe adverse events and health inequalities; exploratory analyses of these data suggest no meaningful impact. We identified a dearth of evidence for home and community-based settings (e.g. delivered through local youth groups), for children living with disabilities and indicators of health inequities.

The Cochrane database of systematic reviews · meta-analysis · 40 citationsread the source →

Benefits of Early Versus Delayed Palliative Care to Informal Family Caregivers of Patients With Advanced Cancer: Outcomes From the ENABLE III Randomized Controlled Trial.

Purpose: To determine the effect of early versus delayed initiation of a palliative care intervention for family caregivers (CGs) of patients with advanced cancer. Patients and methods: Between October 2010 and March 2013, CGs of patients with advanced cancer were randomly assigned to receive three structured weekly telephone coaching sessions, monthly follow-up, and a bereavement call either early after enrollment or 3 months later. CGs of patients with advanced cancer were recruited from a National Cancer Institute cancer center, a Veterans Administration Medical Center, and two community outreach clinics. Outcomes were quality of life (QOL), depression, and burden (objective, stress, and demand). Results: A total of 122 CGs (early, n = 61; delayed, n = 61) of 207 patients participated; average age was 60 years, and most were female (78.7%) and white (92.6%). Between-group differences in depression scores from enrollment to 3 months (before delayed group started intervention) favored the early group (mean difference, -3.4; SE, 1.5; d = -.32; P = .02). There were no differences in QOL (mean difference, -2; SE, 2.3; d = -.13; P = .39) or burden (objective: mean difference, 0.3; SE, .7; d = .09; P = .64; stress: mean difference, -.5; SE, .5; d = -.2; P = .29; demand: mean difference, 0; SE, .7; d = -.01; P = .97). In decedents' CGs, a terminal decline analysis indicated between-group differences favoring the early group for depression (mean difference, -3.8; SE, 1.5; d = -.39; P = .02) and stress burden (mean difference, -1.1; SE, .4; d = -.44; P = .01) but not for QOL (mean difference, -4.9; SE, 2.6; d = -.3; P = .07), objective burden (mean difference, -.6; SE, .6; d = -.18; P = .27), or demand burden (mean difference, -.7; SE, .6; d = -.23; P = .22). Conclusion: Early-group CGs had lower depression scores at 3 months and lower depression and stress burden in the terminal decline analysis. Palliative care for CGs should be initiated as early as possible to maximize benefits.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 342 citationsread the source →

Anxiety and Emotional Intelligence: Comparisons Between Combat Sports, Gender and Levels Using the Trait Meta-Mood Scale and the Inventory of Situations and Anxiety Response.

The present study compared emotional intelligence and anxiety between six combat sports of lower, intermediate and high-level female and male athletes. The sample was composed by 444 athletes (age: 24.7 ± 8.8 years, body mass: 72.4 ± 12.1 kg, height: 1.82 ± 0.3 m, and practice time: 13.1 ± 7.4 years) separated by sex (male n = 273, female n = 171) from different combat sports (jiu-jitsu n = 142, judo n = 137, karate n = 57, kendo n = 63, taekwondo n = 25, and freestyle wrestling n = 20) of three levels (high-level n = 57, intermediate n = 137 and low-level n = 142). Inventory of situations and anxiety response (ISRA) provided an independent evaluation for the three systems: cognitive, motor and physiological, as well as a total with four factors of analysis (anxiety before the evaluation, interpersonal, phobic and before habitual, and daily situations). Trait Meta-Mood Scale (TMMS-24) verified emotional intelligence scales. Descriptive results are demonstrated by percentage or median (first quartile Q1; third quartile Q3), Kruskal-Wallis and Mann-Whitney tests were conducted to compare groups, p ≤ 0.05. The main results demonstrated 10% more total anxiety for wrestling and judo compared to the other groups (p ≤ 0.05). Female athletes showed 15% more anxiety than men, while emotional attention demonstrated 10% better results for women. Significant differences were observed between high- versus low-level athletes in the total anxiety with 85 (44; 143) versus 122 (69; 186) of ISRA index and emotional repair with 30 (25; 34) versus 27 (22; 32) of TMMS-24 index. Emotional intelligence seems to be higher in female and in higher level, while anxiety appears to be prevalent in judo and wrestling, low-level and in female athletes. These outcomes provide support for the hypothesis that emotional abilities are an important contributor to emotional intelligence, particularly differentiating high level athletes than other levels. Results can be incorporated into strategies for reducing anxiety and improving emotional intelligence, considering particularities of gender and level groups.

Frontiers in psychology · 25 citationsread the source →

Timely initiation of breastfeeding in Zimbabwe: evidence from the demographic and health surveys 1994-2015.

Background: Timely initiation of breastfeeding or breastfeeding within 60 min of birth has been shown to be associated with significantly lower risk of infant mortality. The World Health Organization recommends starting breastfeeding within the first hour of birth, yet many women in sub-Saharan Africa do not observe this recommendation. To date, there is limited evidence of timely initiation of breastfeeding for Zimbabwe. Therefore, we undertook this study with the aim of calculating the trend in timely initiation of breastfeeding and to explore the correlates. Methods: We used five rounds of Zimbabwe Demographic and Health Survey data conducted between 1999 and 2015. Participants were 15,923 mothers currently breastfeeding or who had a childbirth within five years preceding the surveys. Outcome variable was self-reported timing of timely breastfeeding for singleton births which was categorized as early (< 60 min), late (≥ 60 min to < 2 4 h) and very late (≥ 24 h). Results: Prevalence of timely initiation of breastfeeding was 60.3% (95% Confidence Interval [CI] 57.44, 63.02) in 1999, 66.9% (95% CI 64.32, 69.4) in 2006, 65.8% (95% CI 63.7, 67.8) in 2011 and 58.3% (95% CI 56.3, 60.4) in 2015. It increased by 27 and 22% in 2006 and 2011 compared with that of the 1999 level respectively. We found no socio-economic and gender-based differentials in the prevalence of timely initiation of breastfeeding. Compared with women aged 15-19 years old, women 25-29 and 30-34 years old had higher odds of practicing timely initiation of breastfeeding. The odds of practicing timely initiation of breastfeeding among Muslim women (adjusted odds ratio [aOR] 1.2, 95% CI 1.07, 1.36) was 20% higher when compared with Christian mothers. Women who wanted to have their last child later (aOR 0.89, 95% CI 0.81, 0.97) had 11% lower odd of practicing timely initiation of breastfeeding when compared with women who wanted children then. Conclusions: The prevalence of timely initiation of breastfeeding in Zimbabwe was 58.3% in 2015, well over the 50% target recommended by WHO for all countries to attain by 2025.

International breastfeeding journal · 12 citationsread the source →

Suicide in children and young people in England: a consecutive case series.

Background: There is concern about the mental health of children and young people and a possible rise in suicidal behaviour in this group. We have done a comprehensive national multi-agency study of suicide in under 20s in England. We aimed to establish how frequently suicide is preceded by child-specific and young person-specific suicide risk factors, as well as all-age factors, and to identify contact with health-care and social-care services and justice agencies. Methods: This study is a descriptive examination of suicide in a national consecutive sample of children and young people younger than 20 years who died by suicide in England between Jan 1, 2014, and April 30, 2015. We obtained general population mortality data from the Office for National Statistics (ONS). We collected information about antecedents considered to be relevant to suicide (eg, abuse, bullying, bereavement, academic pressures, self-harm, and physical health) from a range of investigations and inquiries, including coroner inquest hearings, child death investigations, criminal justice system reports, and the National Health Service, including data on people in contact with mental health services in the 12 months before their death. Findings: 145 suicides in people younger than 20 years were notified to us during the study period, of which we were able to obtain report data about antecedents for 130 (90%). The number of suicides rose sharply during the late teens with 79 deaths by suicide in people aged 18-19 years compared with 66 in people younger than 18 years. 102 (70%) deaths were in males. 92 (63%) deaths were by hanging. Various antecedents were reported among the individuals for whom we had report data, including academic (especially exam) pressures (35 [27%] individuals), bullying (28 [22%]), bereavement (36 [28%]), suicide in family or friends (17 [13%]), physical health conditions (47 [36%]), family problems (44 [34%]), social isolation or withdrawal (33 [25%]), child abuse or neglect (20 [15%]), excessive drinking (34 [26%]), and illicit drug use (38 [29%]). Suicide-related internet use was recorded in 30 (23%) cases. In the week before death 13 (10%) individuals had self-harmed and 35 (27%) had expressed suicidal ideas. 56 (43%) individuals had no known contact with health-care and social-care services or justice agencies. Interpretation: Improved services for self-harm and mental health are crucial to suicide prevention, but the wide range of antecedents emphasises the roles of schools, primary care, social services, and the youth justice system. Funding: The Healthcare Quality Improvement Partnership.

The lancet. Psychiatry · 71 citationsread the source →

Focused psychosocial interventions for children in low-resource humanitarian settings: a systematic review and individual participant data meta-analysis.

Background: Results from studies evaluating the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in humanitarian settings in low-income and middle-income countries have been inconsistent, showing varying results by setting and subgroup (eg, age or gender). We aimed to assess the effectiveness of these interventions, and to explore which children are likely to benefit most. Methods: We did a systematic review and meta-analysis of individual participant data (IPD) from 3143 children recruited to 11 randomised controlled trials of focused psychosocial support interventions versus waiting list. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, PsycArticles, Web of Science, and the main local low-income and middle-income countries (LMICs) databases according to the list of databases relevant to LMIC developed collaboratively by Cochrane and WHO Library, up to November, 2016. We included randomised controlled trials that assessed the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in LMICs, compared with waiting lists (eg, inactive controls). We excluded quasi-randomised trials, studies that did not focus on psychosocial support interventions, and studies that compared two active interventions without control conditions. We requested anonymised data from each trial for each of the prespecified variables for each child who was randomly assigned. The main outcomes considered were continuous scores in post-traumatic stress disorder (PTSD) symptoms, depressive symptoms, and anxiety symptoms assessed with rating scales administered immediately (0-4 weeks) after the intervention. We harmonised all individual items from rating scales using item response theory methods. This study is registered with PROSPERO, number CRD42013006960. Findings: We identified a beneficial effect of focused psychosocial support interventions on PTSD symptoms (standardised mean difference [SMD] -0·33, 95% CI -0·52 to -0·14) that was maintained at follow-up (-0·21, -0·42 to -0·01). We also identified benefits at the endpoint for functional impairment (-0·29, -0·43 to -0·15) and for strengths: coping (-0·22, -0·43 to -0·02), hope (-0·29, -0·48 to -0·09), and social support (-0·27, -0·52 to -0·02). In IPD meta-analyses focused on age, gender, displacement status, region, and household size we found a stronger improvement in PTSD symptoms in children aged 15-18 years (-0·43, -0·63 to -0·23), in non-displaced children (-0·40, -0·52 to -0·27), and in children living in smaller households (<6 members; -0·27, -0·42 to -0·11). Interpretation: Overall, focused psychosocial interventions are effective in reducing PTSD and functional impairment, and in increasing hope, coping, and social support. Future studies should focus on strengthening interventions for younger children, displaced children, and children living in larger households. Funding: European Commission FP7th Framework Programme for Research (Marie Curie International Outgoing Fellowship) and the National Institute on Aging.

The Lancet. Global health · meta-analysis · 99 citationsread the source →

The prevalence and risk factors of mental problems in medical students during COVID-19 pandemic: A systematic review and meta-analysis.

Background: This meta-analysis and systematic review aimed to evaluate the global prevalence and risk factors of mental problems (i.e., depression, anxiety, stress, sleep disorder, posttraumatic stress disorder (PTSD), burnout, psychological distress, and suicidal ideation) among medical students during the COVID-19 pandemic. Method: We searched PubMed, Embase, Web of Science, psycARTICLES, PsycINFO, CNKI, and Wan Fang for studies on the prevalence of mental problems among medical students from January 1, 2020, to April 1, 2022. The pooled prevalence was calculated by random-effect models. We performed a narrative review to identify the risk factors. Results: The meta-analysis included 201 studies (N = 198,000). The prevalence of depression (41 %, 95 % CI, 37-45 %,), anxiety (38 %,95 % CI, 34 %-42 %), stress (34 %, 95 % CI, 27 %-42 %), sleep disorder (52 %, 95 % CI, 44 %-60 %), psychological distress (58 %, 95 % CI, 51 %-65 %), PTSD (34 %, 95 % CI, 22 %-46 %), suicidal ideation (15 %, 95 % CI, 11 %-18 %) and burnout (38 %, 95 % CI, 25 %-50 %) was high. The major risk factors were being female, being junior or preclinical students, exposure to COVID-19, academic stress, psychiatric or physical disorders history, economic trouble, fear of education impairment, online learning trouble, fear of infection, loneliness, low physical activity, low social support, problematic internet or smartphone use, and young age. Limitations: Most studies were cross-sectional. Few studies provided a reasonable response rate, suggesting potential selection bias. Conclusions: The study demonstrated a high prevalence and risk factors for mental problems during COVID-19, calling for mental health services. Our findings are valuable for college and health authorities to identify high-risk students and provide targeted intervention.

Journal of affective disorders · meta-analysis · 154 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Effect of psychological therapy on disease activity, psychological comorbidity, and quality of life in inflammatory bowel disease: a systematic review and meta-analysis.

Background: Inflammatory bowel disease is associated with psychological comorbidity and impaired quality of life. Psychological comorbidity could affect the natural history of inflammatory bowel disease. Psychological therapies might therefore have beneficial effects on disease activity, mood, and quality of life in patients with inflammatory bowel disease. We did a systematic review and meta-analysis examining these issues. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for articles published between 1947 and Sept 22, 2016. Randomised controlled trials (RCTs) recruiting patients with inflammatory bowel disease aged at least 16 years that compared psychological therapy with a control intervention or usual treatment were eligible. We pooled dichotomous data to obtain relative risks of induction of remission in active disease or prevention of relapse of quiescent disease, with 95% CIs. We pooled continuous data to estimate standardised mean differences in disease activity indices, anxiety, depression, perceived stress, and quality-of-life scores in patients dichotomised into those with clinically active or quiescent disease, with 95% CIs. We extracted data from published reports and contacted the original investigators of studies for which the required data were not available. We pooled all data using a random-effects model. Findings: The search identified 1824 studies, with 14 RCTs of 1196 patients eligible for inclusion. The relative risk of relapse of quiescent inflammatory bowel disease with psychological therapy versus control was 0·98 (95% CI 0·77-1·24; p=0·87; I2=50%; six trials; 518 patients). We observed a significant difference in depression scores (standardised mean difference -0·17 [-0·33 to -0·01]; p=0·04; I2=0%; seven trials; 605 patients) and quality of life (0·30 [0·07-0·52]; p=0·01; I2=42%; nine trials; 578 patients) with psychological therapy versus control at the end of therapy for patients with quiescent disease. However, these beneficial effects were lost at final point of follow-up (depression scores -0·11 [-0·27 to 0·05], p=0·17, I2=0%, eight trials, 593 patients; quality of life 0·15 [-0·05 to 0·34], p=0·14, I2=22%, ten trials, 577 patients). When we assessed the effect of individual physiological therapies on quality of life, only cognitive behavioural therapy had any significant beneficial effect (0·37 [0·02-0·72]). We noted no effect on disease activity indices or other psychological wellbeing scores when compared with control in patients with quiescent disease. Dichotomous data for induction of remission and continuous data for change in clinical disease activity indices, depression, anxiety, and perceived stress scores were only reported in one RCT of patients with active disease. Quality of life was assessed in two RCTs of patients with active disease, but was not significantly different between intervention and control groups (0·27 [-0·05 to 0·59]). Interpretation: Psychological therapies, and cognitive behavioural therapy in particular, might have small short-term beneficial effects on depression scores and quality of life in patients with inflammatory bowel disease. Further RCTs of these interventions in patients with coexistent psychological distress are required. Funding: None.

The lancet. Gastroenterology & hepatology · meta-analysis · 163 citationsread the source →

The effectiveness of third wave cognitive behavioural therapies for children and adolescents: A systematic review and meta-analysis.

Objectives: Third wave cognitive behavioural therapies are increasingly used with children and adolescents. This meta-analysis aimed to determine the effectiveness of four third-wave interventions (acceptance and commitment therapy, compassion focused therapy, mindfulness-based cognitive therapy, and metacognitive therapy) for youth. Methods: Four electronic databases were used to identify randomized controlled trials, which tested effects related to health, well-being and functioning. Sensitivity analyses considering study quality were conducted and moderators were explored. Results: The results based on 50 RCTs meeting inclusion criteria indicated emotional symptoms/internalizing problems (g = -.68, 95% CI -.98 to -.37, k = 43, N = 3265), behavioural difficulties/externalizing problems (g = -.62, 95% CI -1.01 to -.22, k = 23, N = 1659), interference from difficulties (g = -.46, 95% CI -.87 to -.05, k = 21, N = 1786), third wave processes (g = .39, 95% CI .17 to .62, k = 22, N = 1900), wellbeing/flourishing (g = .76, 95% CI .35 to 1.17, k = 21, N = 1303) and physical health/pain (g = .72, 95% CI .01 to 1.44, k = 9, N = 1171) yielded significant effects. Effect for quality of life (g = .62, 95% CI -.08 to 1.31, k = 12, N = 1271) was non-significant. When analysing only those studies rated moderate-high quality, third wave interventions yielded significant superiority effects compared to controls for emotional symptoms/internalizing problems (g = -.55, 95% CI -.82 to -.27, k = 28, N = 2110), interference from difficulties (g = -.48, 95% CI -.90 to -.05, k = 21, N = 1605), third wave processes (g = .27, 95% CI .11 to .43, k = 18, N = 1692), well-being/flourishing (g = .50, 95% CI .18 to .81, k = 16, N = 1063), and quality of life (g = .32, 95% CI .04 to .60, k = 10, N = 1212). Behavioural difficulties/externalizing problems (g = -.38, 95% CI -.86 to .10, k = 15, N = 1351) and physical health/pain (g = .52, 95% CI -.14 to 1.17, k = 8, N = 1139) ceased to be significant. Widespread heterogeneity raised concerns about generalizability and follow-up data was relatively sparse. Conclusions: This meta-analysis finds promising results for use of third wave CBT with youth, though the review has limitations.

The British journal of clinical psychology · meta-analysis · 19 citationsread the source →

Exercise training for bronchiectasis.

Background: Bronchiectasis is characterised by excessive sputum production, chronic cough, and acute exacerbations and is associated with symptoms of dyspnoea and fatigue, which reduce exercise tolerance and impair quality of life. Exercise training in isolation or in conjunction with other interventions is beneficial for people with other respiratory diseases, but its effects in bronchiectasis have not been well established. Objectives: To determine effects of exercise training compared to usual care on exercise tolerance (primary outcome), quality of life (primary outcome), incidence of acute exacerbation and hospitalisation, respiratory and mental health symptoms, physical function, mortality, and adverse events in people with stable or acute exacerbation of bronchiectasis. Search methods: We identified trials from the Cochrane Airways Specialised Register, ClinicalTrials.gov, and the World Health Organization trials portal, from their inception to October 2020. We reviewed respiratory conference abstracts and reference lists of all primary studies and review articles for additional references. Selection criteria: We included randomised controlled trials in which exercise training of at least four weeks' duration (or eight sessions) was compared to usual care for people with stable bronchiectasis or experiencing an acute exacerbation. Co-interventions with exercise training including education, respiratory muscle training, and airway clearance therapy were permitted if also applied as part of usual care. Data collection and analysis: Two review authors independently screened and selected trials for inclusion, extracted outcome data, and assessed risk of bias. We contacted study authors for missing data. We calculated mean differences (MDs) using a random-effects model. We used the GRADE approach to assess the certainty of evidence. Main results: We included six studies, two of which were published as abstracts, with a total of 275 participants. Five studies were undertaken with people with clinically stable bronchiectasis, and one pilot study was undertaken post acute exacerbation. All studies included co-interventions such as instructions for airway clearance therapy and/or breathing strategies, provision of an educational booklet, and delivery of educational sessions. The duration of training ranged from six to eight weeks, with a mix of supervised and unsupervised sessions conducted in the outpatient or home setting. No studies of children were included in the review; however we identified two studies as currently ongoing. No data were available regarding physical activity levels or adverse events. For people with stable bronchiectasis, evidence suggests that exercise training compared to usual care improves functional exercise tolerance as measured by the incremental shuttle walk distance, with a mean difference (MD) between groups of 87 metres (95% confidence interval (CI) 43 to 132 metres; 4 studies, 161 participants; low-certainty evidence). Evidence also suggests that exercise training improves six-minute walk distance (6MWD) (MD between groups of 42 metres, 95% CI 22 to 62; 1 study, 76 participants; low-certainty evidence). The magnitude of these observed mean changes appears clinically relevant as they exceed minimal clinically important difference (MCID) thresholds for people with chronic lung disease. Evidence suggests that quality of life improves following exercise training according to St George's Respiratory Questionnaire (SGRQ) total score (MD -9.62 points, 95% CI -15.67 to -3.56 points; 3 studies, 160 participants; low-certainty evidence), which exceeds the MCID of 4 points for this outcome. A reduction in dyspnoea (MD 1.0 points, 95% CI 0.47 to 1.53; 1 study, 76 participants) and fatigue (MD 1.51 points, 95% CI 0.80 to 2.22 points; 1 study, 76 participants) was observed following exercise training according to these domains of the Chronic Respiratory Disease Questionnaire. However, there was no change in cough-related quality of life as measured by the Leicester Cough Questionnaire (LCQ) (MD -0.09 points, 95% CI -0.98 to 0.80 points; 2 studies, 103 participants; moderate-certainty evidence), nor in anxiety or depression. Two studies reported longer-term outcomes up to 12 months after intervention completion; however exercise training did not appear to improve exercise capacity or quality of life more than usual care. Exercise training reduced the number of acute exacerbations of bronchiectasis over 12 months in people with stable bronchiectasis (odds ratio 0.26, 95% CI 0.08 to 0.81; 1 study, 55 participants). After an acute exacerbation of bronchiectasis, data from a single study (N = 27) suggest that exercise training compared to usual care confers little to no effect on exercise capacity (MD 11 metres, 95% CI -27 to 49 metres; low-certainty evidence), SGRQ total score (MD 6.34 points, 95%CI -17.08 to 29.76 points), or LCQ score (MD -0.08 points, 95% CI -0.94 to 0.78 points; low-certainty evidence) and does not reduce the time to first exacerbation (hazard ratio 0.83, 95% CI 0.31 to 2.22). Authors' conclusions: This review provides low-certainty evidence suggesting improvement in functional exercise capacity and quality of life immediately following exercise training in people with stable bronchiectasis; however the effects of exercise training on cough-related quality of life and psychological symptoms appear to be minimal. Due to inadequate reporting of methods, small study numbers, and variation between study findings, evidence is of very low to moderate certainty. Limited evidence is available to show longer-term effects of exercise training on these outcomes.

The Cochrane database of systematic reviews · meta-analysis · 29 citationsread the source →

Prevalence of psychological morbidities among general population, healthcare workers and COVID-19 patients amidst the COVID-19 pandemic: A systematic review and meta-analysis.

This review was done to synthesize the existing evidence on the prevalence of various psychological morbidities among general public, healthcare workers and COVID-19 patients amidst this pandemic situation. Systematic searches were conducted in various databases and search engines such as Medline, Chinese national knowledge infrastructure, Cochrane library, ScienceDirect, and Google Scholar from inception until 22 April 2020. Newcastle Ottawa scale was used to assess the quality of included studies. We carried out a meta-analysis with random-effects model and reported pooled prevalence with 95% confidence intervals (CIs).A total of 50 studies were included in the review. Only seven studies (14%) had low risk of bias. Pooled prevalence rate of psychological morbidities includes poor sleep quality (40%), stress (34%), psychological distress (34%), insomnia (30%), post-traumatic stress symptoms (27%), anxiety (26%), depression (26%). Pooled prevalence rate of psychological morbidities with respect to impact of event due to COVID-19 pandemic was 44% (95%CI-42% to 47%). The burden of these psychological morbidities was highest among the COVID-19 patients followed by healthcare workers and general population.

Psychiatry research · meta-analysis · 355 citationsread the source →

Alcoholics Anonymous and other 12-step programs for alcohol use disorder.

Background: Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted. Objectives: To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets. Search methods: We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, CINAHL and PsycINFO from inception to 2 August 2019. We searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 15 November 2018. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and bibliographies of included studies. Selection criteria: We included randomized controlled trials (RCTs), quasi-RCTs and non-randomized studies that compared AA or TSF (AA/TSF) with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants, or no treatment. We also included healthcare cost offset studies. Participants were non-coerced adults with AUD. Data collection and analysis: We categorized studies by: study design (RCT/quasi-RCT; non-randomized; economic); degree of standardized manualization (all interventions manualized versus some/none); and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). For analyses, we followed Cochrane methodology calculating the standard mean difference (SMD) for continuous variables (e.g. percent days abstinent (PDA)) or the relative risk (risk ratios (RRs)) for dichotomous variables. We conducted random-effects meta-analyses to pool effects wherever possible. Main results: We included 27 studies containing 10,565 participants (21 RCTs/quasi-RCTs, 5 non-randomized, and 1 purely economic study). The average age of participants within studies ranged from 34.2 to 51.0 years. AA/TSF was compared with psychological clinical interventions, such as MET and CBT, and other 12-step program variants. We rated selection bias as being at high risk in 11 of the 27 included studies, unclear in three, and as low risk in 13. We rated risk of attrition bias as high risk in nine studies, unclear in 14, and low in four, due to moderate (> 20%) attrition rates in the study overall (8 studies), or in study treatment group (1 study). Risk of bias due to inadequate researcher blinding was high in one study, unclear in 22, and low in four. Risks of bias arising from the remaining domains were predominantly low or unclear. AA/TSF (manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) RCTs comparing manualized AA/TSF to other clinical interventions (e.g. CBT), showed AA/TSF improves rates of continuous abstinence at 12 months (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 2 studies, 1936 participants; high-certainty evidence). This effect remained consistent at both 24 and 36 months. For percentage days abstinent (PDA), AA/TSF appears to perform as well as other clinical interventions at 12 months (mean difference (MD) 3.03, 95% CI -4.36 to 10.43; 4 studies, 1999 participants; very low-certainty evidence), and better at 24 months (MD 12.91, 95% CI 7.55 to 18.29; 2 studies, 302 participants; low-certainty evidence) and 36 months (MD 6.64, 95% CI 1.54 to 11.75; 1 study, 806 participants; low-certainty evidence). For longest period of abstinence (LPA), AA/TSF may perform as well as comparison interventions at six months (MD 0.60, 95% CI -0.30 to 1.50; 2 studies, 136 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at 12 months, as measured by drinks per drinking day (DDD) (MD -0.17, 95% CI -1.11 to 0.77; 1 study, 1516 participants; moderate-certainty evidence) and percentage days heavy drinking (PDHD) (MD -5.51, 95% CI -14.15 to 3.13; 1 study, 91 participants; low-certainty evidence). For alcohol-related consequences, AA/TSF probably performs as well as other clinical interventions at 12 months (MD -2.88, 95% CI -6.81 to 1.04; 3 studies, 1762 participants; moderate-certainty evidence). For alcohol addiction severity, one study found evidence of a difference in favor of AA/TSF at 12 months (P < 0.05; low-certainty evidence). AA/TSF (non-manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) For the proportion of participants completely abstinent, non-manualized AA/TSF may perform as well as other clinical interventions at three to nine months follow-up (RR 1.71, 95% CI 0.70 to 4.18; 1 study, 93 participants; low-certainty evidence). Non-manualized AA/TSF may also perform slightly better than other clinical interventions for PDA (MD 3.00, 95% CI 0.31 to 5.69; 1 study, 93 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at nine months, as measured by DDD (MD -1.76, 95% CI -2.23 to -1.29; 1 study, 93 participants; very low-certainty evidence) and PDHD (MD 2.09, 95% CI -1.24 to 5.42; 1 study, 286 participants; low-certainty evidence). None of the RCTs comparing non-manualized AA/TSF to other clinical interventions assessed LPA, alcohol-related consequences, or alcohol addiction severity. Cost-effectiveness studies In three studies, AA/TSF had higher healthcare cost savings than outpatient treatment, CBT, and no AA/TSF treatment. The fourth study found that total medical care costs decreased for participants attending CBT, MET, and AA/TSF treatment, but that among participants with worse prognostic characteristics AA/TSF had higher potential cost savings than MET (moderate-certainty evidence). Authors' conclusions: There is high quality evidence that manualized AA/TSF interventions are more effective than other established treatments, such as CBT, for increasing abstinence. Non-manualized AA/TSF may perform as well as these other established treatments. AA/TSF interventions, both manualized and non-manualized, may be at least as effective as other treatments for other alcohol-related outcomes. AA/TSF probably produces substantial healthcare cost savings among people with alcohol use disorder.

The Cochrane database of systematic reviews · meta-analysis · 192 citationsread the source →

Social network interventions for health behaviours and outcomes: A systematic review and meta-analysis.

Background: There has been a growing interest in understanding the effects of social networks on health-related behaviour, with a particular backdrop being the emerging prominence of complexity or systems science in public health. Social network interventions specifically use or alter the characteristics of social networks to generate, accelerate, or maintain health behaviours. We conducted a systematic review and meta-analysis to investigate health behaviour outcomes of social network interventions. Methods and findings: We searched eight databases and two trial registries from 1990 to May 28, 2019, for English-language reports of randomised controlled trials (RCTs) and before-and-after studies investigating social network interventions for health behaviours and outcomes. Trials that did not specifically use social networks or that did not include a comparator group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of health behaviours or outcomes at ≤6 months was assessed by random-effects meta-analysis. Secondary outcomes included those measures at >6-12 months and >12 months. This study is registered with the International Prospective Register of Systematic Reviews, PROSPERO: CRD42015023541. We identified 26,503 reports; after exclusion, 37 studies, conducted between 1996 and 2018 from 11 countries, were eligible for analysis, with a total of 53,891 participants (mean age 32.4 years [SD 12.7]; 45.5% females). A range of study designs were included: 27 used RCT/cluster RCT designs, and 10 used other study designs. Eligible studies addressed a variety of health outcomes, in particular sexual health and substance use. Social network interventions showed a significant intervention effect compared with comparator groups for sexual health outcomes. The pooled odds ratio (OR) was 1.46 (95% confidence interval [CI] 1.01-2.11; I2 = 76%) for sexual health outcomes at ≤6 months and OR 1.51 (95% CI 1.27-1.81; I2 = 40%) for sexual health outcomes at >6-12 months. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in haemoglobin A1c (HbA1c), and smoking cessation. Because of clinical and measurement heterogeneity, it was not appropriate to pool data on these other behaviours in a meta-analysis. For sexual health outcomes, prespecified subgroup analyses were significant for intervention approach (p < 0.001), mean age of participants (p = 0.002), and intervention length (p = 0.05). Overall, 22 of the 37 studies demonstrated a high risk of bias, as measured by the Cochrane Risk of Bias tool. The main study limitations identified were the inclusion of studies of variable quality; difficulty in isolating the effects of specific social network intervention components on health outcomes, as interventions included other active components; and reliance on self-reported outcomes, which have inherent recall and desirability biases. Conclusions: Our findings suggest that social network interventions can be effective in the short term (<6 months) and longer term (>6 months) for sexual health outcomes. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in HbA1c, and smoking cessation.

PLoS medicine · meta-analysis · 211 citationsread the source →

Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age.

Objective: Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants. Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities. The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously. Methods: Nutrition data including enteral and parenteral feeds were collected prospectively, and follow-up assessments of 1035 extremely low birth weight infants at 18 months' corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14, 1999, and June 25, 2001. Total volume of breast milk feeds (mL/kg per day) during hospitalization was calculated. Neonatal characteristics and morbidities, interim history, and neurodevelopmental and growth outcomes at 18 to 22 months' corrected age were assessed. Results: There were 775 (74.9%) infants in the breast milk and 260 (25.1%) infants in the no breast milk group. Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity, including number of days of hospitalization. Mean age of first day of breast milk for the breast milk infants was 9.3 +/- 9 days. Infants in the breast milk group began to ingest non-breast milk formula later (22.8 vs 7.3 days) compared with the non-breast milk group. Age at achieving full enteral feeds was similar between the breast milk and non-breast milk groups (29.0 +/- 18 vs 27.4 +/- 15). Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non-breast milk groups, respectively. At discharge, 30.6% of infants in the breast milk group still were receiving breast milk. Mothers in the breast milk group were significantly more likely to be white (42% vs 27%), be married (50% vs 30%), have a college degree (22% vs 6%), and have private health insurance (34% vs 18%) compared with the no breast milk group. Mothers who were black, had a low household income (< or = dollar 20000), or had higher parity were less likely to provide breast milk feeds. The analysis of outcomes between the any human milk and no human milk groups were adjusted for maternal age, maternal education, marital status, race/ethnicity, and the other standard covariates. Children in the breast milk group were more likely to have a Bayley Mental Development Index > or = 85, higher mean Bayley Psychomotor Development Index, and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement, motor regulation, and total score. There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups. There were no differences in the mean weight (10.4 kg vs 10.4 kg), length (80.5 cm vs 80.5 cm), or head circumference (46.8 cm vs 46.6 cm) for the breast milk and no breast milk groups, respectively, at 18 months. Multivariate analyses, adjusting for confounders, confirmed a significant independent association of breast milk on all 4 primary outcomes: the mean Bayley (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and incidence of rehospitalization). For every 10-mL/kg per day increase in breast milk ingestion, the Mental Development Index increased by 0.53 points, the Psychomotor Development Index increased by 0.63 points, the Behavior Rating Scale percentile score increased by 0.82 points, and the likelihood of rehospitalization decreased by 6%. In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores, the mean volume of breast milk per kilogram per day during the hospitalization was calculated, and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders. Overall, the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant. There was a 14.0% difference in Behavior Rating Scale scores between the lowest and highest quintiles. For the outcomes (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and Rehospitalization <1 year), only the values for the >80th percentile quintile of breast milk feeding were significantly different from the no breast milk values. In our adjusted regression analyses, every 10 mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index; therefore, the impact of breast milk ingestion during the hospitalization for infants in the highest quintile (110 mL/kg per day) on the Bayley Mental Development Index would be 10 x 0.53, or 5.3 points. Conclusions: An increase of 5 points potentially would optimize outcomes and decrease costs by decreasing the number of very low birth weight children who require special education services. The societal implications of a 5-point potential difference (one third of an SD) in IQ are substantial. The potential long-term benefit of receiving breast milk in the NICU for extremely low birth weight infants may be to optimize cognitive potential and reduce the need for early intervention and special education services.

Pediatrics · cohort or longitudinal · 344 citationsread the source →

Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review.

Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.

Journal of palliative medicine · systematic review · 135 citationsread the source →

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis.

Background: Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because of the cost and resource constraints of psychological alternatives, but there is a paucity of comparative information for the multiple available drug choices. Methods: A systematic review and network meta-analysis was performed on randomised trials in adult outpatients with generalised anxiety disorder identified from MEDLINE, Web of Science, Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, Drugs@FDA and commercial pharmaceutical registries. Placebo and active control trials were included. Data were extracted from all manuscripts and reports. Primary outcomes were efficacy (mean difference [MD] in change in Hamilton Anxiety Scale Score) and acceptability (study discontinuations for any cause). We estimated summary mean treatment differences and odds ratios using network meta-analyses with random effects. This study is registered with PROSPERO, number CRD42018087106. Findings: Studies were published between Jan 1, 1994 and Aug 1, 2017, in which 1992 potential studies were screened for inclusion. This analysis is based on 89 trials, which included 25 441 patients randomly assigned to 22 different active drugs or placebo. Duloxetine (MD -3·13, 95% credible interval [CrI] -4·13 to -2·13), pregabalin (MD -2·79, 95% CrI -3·69 to -1·91), venlafaxine (MD -2·69, 95% CrI -3·50 to -1·89), and escitalopram (MD -2·45, 95% CrI -3·27 to -1·63) were more efficacious than placebo with relatively good acceptability. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also found to be efficacious and well tolerated but these findings were limited by small sample sizes. Quetiapine (MD -3·60 95% CrI -4·83 to -2·39) had the largest effect on HAM-A but it was poorly tolerated (odds ratio 1·44, 95% CrI 1·16-1·80) when compared with placebo. Likewise, paroxetine and benzodiazepines were effective but also poorly tolerated when compared with placebo. Risk of reporting bias was considered low, and when possible all completed studies were included to avoid publication bias. Interpretation: To our knowledge, this is the largest contemporary review of pharmacological agents for the treatment of generalised anxiety disorder by use of network analysis. There are several effective treatment choices for generalised anxiety disorder across classes of medication. The failure of initial pharmacological therapy might not be a reason to abandon a pharmacological treatment strategy. Funding: No funding was received for this research.

Lancet (London, England) · systematic review · 217 citationsread the source →

Prevention of Psychosis: Advances in Detection, Prognosis, and Intervention.

Importance: Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective: To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence review: Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings: In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and relevance: This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.

JAMA psychiatry · systematic review · 369 citationsread the source →

Suicide prevention strategies revisited: 10-year systematic review.

Background: Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of suicide prevention interventions since 2005. Methods: We searched PubMed and the Cochrane Library using multiple terms related to suicide prevention for studies published between Jan 1, 2005, and Dec 31, 2014. We assessed seven interventions: public and physician education, media strategies, screening, restricting access to suicide means, treatments, and internet or hotline support. Data were extracted on primary outcomes of interest, namely suicidal behaviour (suicide, attempt, or ideation), and intermediate or secondary outcomes (treatment-seeking, identification of at-risk individuals, antidepressant prescription or use rates, or referrals). 18 suicide prevention experts from 13 European countries reviewed all articles and rated the strength of evidence using the Oxford criteria. Because the heterogeneity of populations and methodology did not permit formal meta-analysis, we present a narrative analysis. Findings: We identified 1797 studies, including 23 systematic reviews, 12 meta-analyses, 40 randomised controlled trials (RCTs), 67 cohort trials, and 22 ecological or population-based investigations. Evidence for restricting access to lethal means in prevention of suicide has strengthened since 2005, especially with regard to control of analgesics (overall decrease of 43% since 2005) and hot-spots for suicide by jumping (reduction of 86% since 2005, 79% to 91%). School-based awareness programmes have been shown to reduce suicide attempts (odds ratio [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and suicidal ideation (0·5, 0·27-0·92; p=0·025). The anti-suicidal effects of clozapine and lithium have been substantiated, but might be less specific than previously thought. Effective pharmacological and psychological treatments of depression are important in prevention. Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care, in general public education and media guidelines. Other approaches that need further investigation include gatekeeper training, education of physicians, and internet and helpline support. The paucity of RCTs is a major limitation in the evaluation of preventive interventions. Interpretation: In the quest for effective suicide prevention initiatives, no single strategy clearly stands above the others. Combinations of evidence-based strategies at the individual level and the population level should be assessed with robust research designs. Funding: The Expert Platform on Mental Health, Focus on Depression, and the European College of Neuropsychopharmacology.

The lancet. Psychiatry · systematic review · 1070 citationsread the source →

Family life events in the first year of acute lymphoblastic leukemia therapy: a children's oncology group report.

Background: Despite higher cure rates, childhood acute lymphoblastic leukemia (ALL) may continue to result in considerable family strain. We sought to (i) measure incidence of divorce, reduced career opportunities, changes to work hours, home relocation, and changes to family planning at one year after ALL diagnosis; and (ii) Identify family and patient factors associated with these events. Procedure: We conducted a prospective cohort study of 159 children with average risk-ALL enrolled and treated on COG protocol AALL0331 at 31 selected sites. Eligibility criteria included age ≥2 years and English or Spanish comprehension. Parents completed surveys at three time points during the first 12 months of therapy. Results: Parents were at significantly increased risk of loss of employment (46% vs. 9.1%, P ≤ 0.001) than peers nationally. 13% divorced/separated, 27% relocated homes, 22% decided not to have more children, 51% declined occupational opportunities, and 68% decreased work hours. In adjusted analyses, relocation correlated with less maternal education (OR: 4.27 [95% CI: 1.43-12.82]). Declining parental opportunities associated with family income <$50,000 (OR: 4.25 [95% CI: 1.50-12.02]) and child <5 years old (OR: 4.21 [95% CI: 1.73-10.25]). Deciding not to have more children correlated with smaller family size 2-3 versus 4-5 (OR: 3.62 [95% CI: 1.10-11.96]). Conclusion: Families experience a high incidence of major life changes in the first year of ALL treatment. Understanding these burdens helps health care providers to provide appropriate anticipatory guidance and support. No unifying factor was associated with the different family events. Ongoing follow-up is planned to measure long-term outcomes.

Pediatric blood & cancer · 39 citationsread the source →

The Agewell trial: a pilot randomised controlled trial of a behaviour change intervention to promote healthy ageing and reduce risk of dementia in later life.

Background: Lifestyle factors represent prime targets for behaviour change interventions to promote healthy ageing and reduce dementia risk. We evaluated a goal-setting intervention aimed at promoting increased cognitive and physical activity and improving mental and physical fitness, diet and health. Methods: This was a pilot randomised controlled trial designed to guide planning for a larger-scale investigation, provide preliminary evidence regarding efficacy, and explore feasibility and acceptability. Primary outcomes were engagement in physical and cognitive activity. Participants aged over 50 living independently in the community were recruited through a community Agewell Centre. Following baseline assessment participants were randomly allocated to one of three conditions: control (IC) had an interview in which information about activities and health was discussed; goal-setting (GS n = 24) had an interview in which they set behaviour change goals relating to physical, cognitive and social activity, health and nutrition; and goal-setting with mentoring (GM, n = 24) had the goal-setting interview followed by bi-monthly telephone mentoring. Participants and researchers were blinded to group assignment. Participants were reassessed after 12 months. Results: Seventy-five participants were randomised (IC n = 27, GS n = 24, GM n = 24). At 12-month follow-up, the two goal-setting groups, taken together (GS n = 21, GM n = 22), increased their level of physical (effect size 0.37) and cognitive (effect size 0.15) activity relative to controls (IC n = 27). In secondary outcomes, the two goal-setting groups taken together achieved additional benefits compared to control (effect sizes ≥ 0.2) in memory, executive function, cholesterol level, aerobic capacity, flexibility, balance, grip strength, and agility. Adding follow-up mentoring produced further benefits compared to goal-setting alone (effect sizes ≥ 0.2) in physical activity, body composition, global cognition and memory, but not in other domains. Implementation of the recruitment procedure, assessment and intervention was found to be feasible and the approach taken was acceptable to participants, with no adverse effects. Conclusions: A brief, low-cost goal-setting intervention is feasible and acceptable, and has the potential to achieve increased activity engagement. Trial registration: Current Controlled Trials ISRCTN30080637.

BMC psychiatry · randomised controlled trial · 39 citationsread the source →

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding: National Institute for Health Research, Health Technology Assessment programme.

The lancet. Psychiatry · randomised controlled trial · 192 citationsread the source →

An online healthy relationship tool and safety decision aid for women experiencing intimate partner violence (I-DECIDE): a randomised controlled trial.

Background: Evidence for online interventions to help women experiencing intimate partner violence is scarce. We assessed whether an online interactive healthy relationship tool and safety decision aid (I-DECIDE) would increase women's self-efficacy and improve depressive symptoms compared with an intimate partner violence information website. Methods: In this two-group pragmatic randomised controlled trial, we enrolled women who had screened positive for any form of intimate partner violence or fear of a partner in the 6 months before recruitment. Women aged 16-50 years currently residing in Australia, who had safe access to a computer and an internet connection, and who answered positively to one of the screening questions in English were eligible for inclusion. Participants were randomly assigned (1:1) by computer to receive either the intervention or control website. The intervention website consisted of modules on healthy relationships, abuse and safety, and relationship priority setting, and a tailored action plan. The control website was a static intimate partner violence information website. As the initial portion of the website containing the baseline questions was identical for both groups, there was no way for women to tell which group they had been allocated to, and the research team were also masked to participant allocation until after analysis of the 12-month data. Data were collected at baseline, immediately after completion of the website, at 6 months, and 12 months. Primary outcomes were mean general self-efficacy score (immediately after website completion, and at 6 months and 12 months) and mean depression score (at 6 months and 12 months). Data analyses were done according to intention-to-treat principles, accounting for missing data, and adjusted for outcome baseline scores. This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN 12614001306606. Findings: Between Jan 16, and Aug 28, 2015, 584 patients registered for the study and were assessed for eligibility. 422 eligible participants were randomly allocated to the intervention group (227 patients) or control group (195 patients). 179 (79%) participants in the intervention group and 156 (80%) participants in the control group completed 12-month follow-up. Mean self-efficacy at 6 months and 12 months was lower for participants in the intervention group than for participants in the control group, although this did not meet the prespecified mean difference (6 months: 27·5 [SD 5·1] vs 28·1 [4·4], imputed mean difference 1·3 [95% CI 0·3 to 2·3]; 12 months: 27·8 [SD 5·4] vs 29·0 [5·0], imputed mean difference 1·6 [95% CI 0·5 to 2·7]). We found no difference between groups in depressive symptoms at 6 months or 12 months (6 months: 22·5 [SD 17·1] vs 24·2 [17·2], imputed mean difference -0·3 [95% CI -3·5 to 3·0]; 12 months: 21·9 [SD 19·3] vs 21·5 [19·3], imputed mean difference -1·9 [95% CI -5·6 to 1·7]). Qualitative findings indicated that participants found the intervention supportive and a motivation for action. Interpretation: Our findings highlight the need for further research, development, and refinement of online interventions for women experiencing intimate partner violence, particularly into the duration needed for interventions. Although we detected no meaningful differences between groups, our qualitative results indicated that some women find an online tool a helpful source of motivation and support. Funding: Australian Research Council.

The Lancet. Public health · randomised controlled trial · 43 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, US-based trial.

Background: A pneumococcal conjugate vaccine (PCV) specifically focused on serotypes associated with adult residual disease burden is urgently needed. We aimed to assess V116, an investigational 21-valent PCV, that contains pneumococcal polysaccharides (PnPs), which account for 74-94% of invasive pneumococcal disease in adults aged 65 years or older. Methods: We did a phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, non-inferiority and superiority trial. The phase 1 study was done at two clinical sites in the USA, and the phase 2 study was done in 18 clinical sites in the USA. Eligible participants were healthy adults with or without chronic medical conditions assessed as stable, aged 18-49 years in the phase 1 trial and aged 50 years or older in the phase 2 trial. Participants were excluded if they had a history of invasive pneumococcal disease or other culture-positive pneumococcal disease within the past 3 years, known hypersensitivity to a vaccine component, known or suspected impairment of immunological function, were pregnant or were breastfeeding, or had previously received any pneumococcal vaccine. Participants had to abstain from sexual activity or use protocol approved contraception. All participants were centrally randomly assigned to a vaccine group using an interactive response technology system. Participants and investigators were masked to group assignment. In phase 1, participants were randomly assigned (1:1:1) to receive a single dose of V116-1 (2 μg per pneumococcal polysaccharide [PnP] per 0·5 mL) or V116-2 (4 μg per PnP per 1·0 mL) or the 23-valent unconjugated PnP vaccine, PPSV23 (25 μg per PnP per 0·5 mL). In phase 2, participants were randomly assigned (1:1) to receive one dose of V116 (4 μg per PnP per 1·0 mL) or PPSV23 (25 μg per PnP per 0·5 mL), stratified by age. Safety analyses included all randomly assigned participants who received study vaccine; immunogenicity analyses were per protocol. For both phases, the primary safety outcome was the proportion of participants with solicited injection-site adverse events and solicited systemic adverse events up to day 5 after vaccination and the proportion of participants with vaccine-related serious adverse events to 6 months after vaccination. In phase 2, primary immunogenicity outcomes were to test non-inferiority of V116 compared with PPSV23 as measured by serotype-specific opsonophagocytic antibody geometric mean titres (OPA-GMT) ratios for the serotypes common to the two vaccines at 30 days after vaccination (using a 0·33 margin) and to test superiority of V116 compared with PPSV23 as measured by serotype-specific OPA-GMT ratios for the serotypes unique to V116 at 30 days after vaccination (using a 1·0 margin). This trial is registered with Clinicaltrials.gov, NCT04168190. Findings: Between Dec 6 and 26, 2019, 92 volunteers were screened and 90 (98%) enrolled for phase 1 (59 [66%] women; 31 [34%] men); 30 participants were assigned to each group and received study vaccine. 30 (100%) participants in the V116-1 group, 29 (97%) in the V116-2 group, and 30 (100%) participants in the PPSV23 group were included in the per-protocol immunogenicity evaluation. From Sept 23, 2020, to Jan 12, 2021, 527 volunteers were screened, and 510 (97%) participants were enrolled in the phase 2 trial. 508 participants (>99%; 254 [100%] of 254 participants randomly assigned to the V116 group and 254 [99%] of 256 randomly assigned to PPSV23 group) received study vaccine (281 [55%] women; 227 [45%] men). 252 (99%) of 254 of participants in the V116 group and 254 (99%) of 256 participants in the PPSV23 group were included in the primary immunogenicity analyses. There were no vaccine-related serious adverse events or vaccine-related deaths in either study phase. In both phases, the most common solicited injection site adverse event was injection site pain (phase 1 22 [73%] participants in V116-1 group, 23 [77%] participants in V116-2 group, and 17 [57%] participants in the PPSV23 group; phase 2 118 [46%] of 254 participants in the V116 group and 96 [38%] of 254 in the PPSV23 group]. The most common solicited systemic adverse events in phase 1 was fatigue (eight [27%] participants in the V116-1 group, eight [27%] participants in the V116-2 group, and five [17%] participants in PPSV23 group) and myalgia (eight [27%] participants in the V116-1 group, nine (30%) participants in the V116-2 group, and four (13%) participants in the PPSV23 group]. In phase 2, the most frequently reported solicited systemic adverse event was fatigue (49 [19%] participants in V116 group, and 31 [12%] participants in PPSV23 group). In both phases, most of the solicited adverse events in all vaccine groups were mild and of short duration (≤3 days). V116 met non-inferiority criteria compared with PPSV23 for the 12 shared serotypes and met superiority criteria compared to PPSV23 for the nine unique serotypes. Interpretation: V116 was well tolerated with a safety profile generally similar to PPSV23; consistent with licensed pneumococcal conjugate vaccines. Functional OPA antibodies were induced to all V116 vaccine serotypes. The vaccine was non-inferior to PPSV23 for the 12 serotypes common to both vaccines and superior to PPSV23 for the nine unique serotypes in V116. Our findings support the development of V116 for prevention of pneumococcal disease in adults. Funding: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA.

The Lancet. Infectious diseases · randomised controlled trial · 73 citationsread the source →

Combined prevention for substance use, depression, and anxiety in adolescence: a cluster-randomised controlled trial of a digital online intervention.

Background: Substance use, depression, and anxiety in adolescence are major public health problems requiring new scalable prevention strategies. We aimed to assess the effectiveness of a combined online universal (ie, delivered to all pupils) school-based preventive intervention targeting substance use, depression, and anxiety in adolescence. Methods: We did a multicentre, cluster-randomised controlled trial in secondary schools in Australia, with pupils in year 8 or 9 (aged 13-14 years). Participating schools were randomly assigned (1:1:1:1) to one of four intervention conditions: (1) Climate Schools-Substance Use, focusing on substance use only; (2) Climate Schools-Mental Health, focusing on depression and anxiety only; (3) Climate Schools-Combined, focusing on the prevention of substance use, depression, and anxiety; or (4) active control. The interventions were delivered in school classrooms in an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. The interventions were delivered for 2 years and primary outcomes were knowledge related to alcohol, cannabis, and mental health; alcohol use, including heavy episodic drinking; and depression and anxiety symptoms at 12, 24, and 30 months after baseline. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785) and an extended follow-up is underway. Findings: Between Sept 1, 2013, and Feb 28, 2014, we recruited 88 schools (12 391 pupils), of whom 71 schools and 6386 (51·5%) pupils were analysed (17 schools dropped out and 1308 pupils declined to participate). We allocated 18 schools (1739 [27·25%] pupils; 1690 [97·2%] completed at least one follow-up) to the substance use condition, 18 schools (1594 [25·0%] pupils; 1560 [97·9%] completed at least one follow-up) to the mental health condition, 16 schools (1497 [23·4%] pupils; 1443 [96·4%] completed at least one follow-up) to the combined condition, and 19 schools (1556 [23·4%] pupils; 1513 [97·2%] completed at least one follow-up) to the control condition. Compared with controls, the combined intervention group had increased knowledge related to alcohol and cannabis at 12, 24, and 30 months (standardised mean difference [SMD] for alcohol 0·26 [95% CI 0·14 to 0·39] and for cannabis 0·17 [0·06 to 0·28] at 30 months), increased knowledge related to mental health at 24 months (0·17 [0·08 to 0·27]), reduced growth in their odds of drinking and heavy episodic drinking at 12, 24, and 30 months (odds ratio for drinking 0·25 [95% CI 0·12 to 0·51], and for heavy episodic drinking 0·15 [0·04 to 0·58] at 30 months), and reduced increases in anxiety symptoms at 12 and 30 months (SMD -0·12 [95% CI -0·22 to -0·01] at 30 months). We found no difference in symptoms or probable diagnosis of depression. The combined intervention group also showed improvement in alcohol use outcomes compared with the substance use and mental health interventions and improvements in anxiety outcomes when compared with the mental health intervention only. Interpretation: Combined online prevention of substance use, depression, and anxiety led to increased knowledge of alcohol, cannabis, and mental health, reduced increase in the odds of any drinking and heavy episodic drinking, and reduced symptoms of anxiety over a 30-month period. These findings provide the first evidence of the effectiveness of an online universal school-based preventive intervention targeting substance use, depression, and anxiety in adolescence. Funding: Australian National Health and Medical Research Council.

The Lancet. Digital health · randomised controlled trial · 62 citationsread the source →

Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial.

Background: New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M1 and M4-preferring muscarinic receptor agonist that does not block D2 dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline-trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of ameliorating xanomeline-related adverse events associated with peripheral muscarinic receptors. The EMERGENT-2 trial aimed to assess the efficacy and safety of KarXT in people with schizophrenia experiencing acute psychosis. Methods: EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia. Participants were adults aged 18-65 years with a diagnosis of schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. The participants were recruited from 22 inpatient sites in the USA, and were randomly assigned (1:1) to KarXT or placebo twice per day. Participants randomly assigned to KarXT received 50 mg xanomeline and 20 mg trospium twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3-7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability. The primary endpoint was change from baseline to week 5 in PANSS total score. Efficacy analyses used the modified intention-to-treat population (all randomly assigned participants who received at least one trial medication dose and had at least one post-baseline PANSS assessment). Least squares mean change from baseline, SE, and least squares mean difference between the KarXT and placebo groups at week 5, along with the 95% CI and two-sided p values were calculated for the primary and secondary continuous efficacy endpoints. Safety analyses included all participants receiving at least one trial medication dose and used descriptive statistics. This trial is registered with ClinicalTrials.gov (NCT04659161). Findings: From Dec 16, 2020, to April 13, 2022, of 407 people who were screened, 252 participants meeting enrolment criteria were randomly assigned to the KarXT (n=126) or placebo (n=126). Baseline PANSS total scores were 98·3 (KarXT; n=126) and 97·9 (placebo; n=125). The trial met the primary endpoint with a mean change from baseline to week 5 in PANSS total score that favoured KarXT (-21·2 points, SE 1·7) versus placebo (-11·6 points, 1·6; least squares mean difference -9·6; 95% CI -13·9 to -5·2; p<0·0001, Cohen's d effect size=0·61). All secondary endpoints were also met, and favoured KarXT versus placebo (p<0·05). The most common adverse events with KarXT versus placebo were constipation (27 [21%] vs 13 [10%]), dyspepsia (24 [19%] vs 10 [8%]), headache (17 [14%] vs 15 [12%]), nausea (24 [19%] vs seven [6%]), vomiting (18 [14%] vs one [1%]), hypertension (12 [10%] vs one [1%]), dizziness (11 [9%] vs four [3%]), gastro-oesophageal reflux disease (eight [6%] vs zero [0%]), and diarrhoea (seven [6%] vs four [3%]). Treatment-emergent adverse event rates of extrapyramidal motor symptoms (KarXT, zero [0%] vs placebo, zero [0%]), akathisia (one [1%] vs one [1%]), weight gain (zero [0%] vs one [1%]), and somnolence (six [5%] vs five [4%]) were similar between the KarXT and placebo groups, as were adverse event-related discontinuation rates (nine [7%] vs seven [6%]). Interpretation: In the EMERGENT-2 trial, KarXT was effective in reducing positive and negative symptoms and was generally well tolerated. These results support the potential for KarXT to represent a new class of effective and well tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications. Results from additional trials, including the identical EMERGENT-3 trial and the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials, will provide additional information on the efficacy and safety of KarXT in people with schizophrenia. Funding: Karuna Therapeutics.

Lancet (London, England) · randomised controlled trial · 144 citationsread the source →

Guided, internet-based, rumination-focused cognitive behavioural therapy (i-RFCBT) versus a no-intervention control to prevent depression in high-ruminating young adults, along with an adjunct assessment of the feasibility of unguided i-RFCBT, in the REducing Stress and Preventing Depression trial (RESPOND): study protocol for a phase III randomised controlled trial

BACKGROUND: Depression is a global health challenge. Prevention is highlighted as a priority to reduce its prevalence. Although effective preventive interventions exist, the efficacy and coverage can be improved. One proposed means to increase efficacy is by using interventions to target specific risk factors, such as rumination. Rumination-focused CBT (RFCBT) was developed to specifically target depressive rumination and reduces acute depressive symptoms and relapse for patients with residual depression in a randomised controlled trial. Preliminary findings from a Dutch randomised prevention trial in 251 high-risk 15- to 22-year-old subjects selected with elevated worry and rumination found that both supported internet-RFBCT and group-delivered RFCBT equally reduced depressive symptoms and the onset of depressive cases over a period of 1 year, relative to the no-intervention control. METHODS/DESIGN: A phase III randomised controlled trial following the Medical Research Council (MRC) Complex Interventions Framework will extend a Dutch trial to the United Kingdom, with the addition of diagnostic interviews, primarily to test whether guided internet-RFCBT reduces the onset of depression relative to a no-intervention control. High-risk young adults (aged 18 to 24 years), selected with elevated worry/rumination and recruited through university and internet advertisement, will be randomised to receive either guided internet-RFCBT, supported by clinical psychologists or mental health paraprofessionals, or a no-intervention control. As an adjunct arm, participants are also randomised to unguided internet-RFCBT self-help to provide an initial test of the feasibility and effect size of this intervention. While participants are also randomised to unguided internet-RFCBT, the trial was designed and powered as a phase III trial comparing guided internet-RFCBT versus a no-intervention control. In the comparison between these two arms, the primary outcomes are as follows: a) onset of major depressive episode over a 12-month period, assessed with a Structured Clinical Interview for Diagnosis at 3 months (post-intervention), 6 months and 15 months after randomisation. The following secondary outcomes will be recorded: the incidence of generalized anxiety disorder, symptoms of depression and anxiety, and levels of worry and rumination, measured at baseline and at the same follow-up intervals. In relation to the pilot investigation of unguided internet-RFCBT (the adjunct intervention arm), we will assess the feasibility and acceptability of the data-collection procedures, levels of attrition, effect size and acceptability of the unguided internet-RFCBT intervention. DISCUSSION: Widespread implementation is necessary for effective prevention, suggesting that the internet may be a valuable mode of delivery. Previous research suggests that guided internet-RFCBT reduces incidence rates relative to controls. We are also interested in developing and evaluating an unguided version to potentially increase the availability and reduce the costs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12683436 . Date of registration: 27 October 2014.

Trials · randomised controlled trial · 145 citationsread the source →

Development and preliminary randomized controlled trial of a distress tolerance treatment for smokers with a history of early lapse.

Introduction: An inability to tolerate distress is a significant predictor of early smoking lapse following a cessation attempt. We conducted a preliminary randomized controlled trial to compare a distress tolerance (DT) treatment that incorporated elements of exposure-based therapies and Acceptance and Commitment Therapy to standard smoking cessation treatment (ST). Methods: Smokers with a history of early lapse in prior quit attempts received either DT (N = 27; 9 2-hr group and 6 50-min individual sessions) or ST (N = 22; 6 90-min group and 1 20-min individual session), plus 8 weeks of transdermal nicotine patch. Results: At the end of behavioral treatment, odds of abstinence among participants receiving DT were 6.46 times greater than among participants receiving ST (66.7% vs. 31.8%), equivalent to a medium- to large-effect size. Odds of abstinence for DT were still 1.73 times greater at 8 weeks, corresponding to a small- to medium-effect size, although neither this difference nor those at 13 and 26 weeks were statistically significant. Furthermore, of those who lapsed to smoking during the first week postquit, DT participants had more than 4 times greater odds of abstinence than ST participants at the end of treatment. Relative to ST, DT participants also reported a larger decrease in experiential avoidance, a hypothesized DT treatment mediator, prior to quit day. The trajectory of negative mood and withdrawal symptoms in DT differed from ST and was largely consistent with hypotheses. Conclusions: Reasons for the decrease in abstinence in DT after treatment discontinuation and suggestions for future research are discussed.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · randomised controlled trial · 56 citationsread the source →

Nutritional intervention to prevent weight gain in patients commenced on olanzapine: a randomized controlled trial.

Objective: Olanzapine is the most commonly prescribed atypical antipsychotic medication in Australia. Research reports an average weight gain of between 4.5 and 7 kg in the 3 months following its commencement. Trying to minimize this weight gain in a population with an already high prevalence of obesity, mortality and morbidity is of clinical and social importance. This randomized controlled trial investigated the impact of individual nutrition education provided by a dietitian on weight gain in the 3 and 6 months following the commencement of olanzapine. Method: Fifty-one individuals (29 females, 22 males) who had started on olanzapine in the previous 3 months (mean length of 27 days +/- 20) were recruited through Peninsula Health Psychiatric Services and were randomly assigned to either the intervention (n = 29) or the control group (n = 22). Individuals in the intervention group received six 1 hour nutrition education sessions over a 3-month period. Weight, waist circumference, body mass index (BMI) and qualitative measures of exercise levels, quality of life, health and body image were collected at baseline at 3 and 6 months. Results: After 3 months, the control group had gained significantly more weight than the treatment group (6.0 kg vs 2.0 kg, p < or = 0.002). Weight gain of more than 7% of initial weight occurred in 64% of the control group compared to 13% of the treatment group. The control group's BMI increased significantly more than the treatment group's (2 kg/m(2)vs 0.7 kg/m(2), p < or = 0.03). The treatment group reported significantly greater improvements in moderate exercise levels, quality of life, health and body image compared to the controls. At 6 months, the control group continued to show significantly more weight gain since baseline than the treatment group (9.9 kg vs 2.0 kg, p < or = 0.013) and consequently had significantly greater increases in BMI (3.2 kg/m(2)vs 0.8 kg/m(2), p < or = 0.017). Conclusion: Individual nutritional intervention provided by a dietitian is highly successful at preventing olanzapine-induced weight gain.

The Australian and New Zealand journal of psychiatry · randomised controlled trial · 94 citationsread the source →

Internet-based intervention for smoking cessation (StopAdvisor) in people with low and high socioeconomic status: a randomised controlled trial.

Background: Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs; however, long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites. We aimed to assess a new interactive internet-based intervention (StopAdvisor) for smoking cessation that was designed with particular attention directed to people with low socioeconomic status. Methods: We did this online randomised controlled trial between Dec 6, 2011, and Oct 11, 2013, in the UK. Participants aged 18 years and older who smoked every day were randomly assigned (1:1) to receive treatment with StopAdvisor or an information-only website. Randomisation was automated with an unseen random number function embedded in the website to establish which treatment was revealed after the online baseline assessment. Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status subpopulations. Participants, and researchers who obtained data and did laboratory analyses, were masked to treatment allocation. The primary outcome was 6 month sustained, biochemically verified abstinence. The main secondary outcome was 6 month, 7 day biochemically verified point prevalence. Analysis was by intention to treat. Homogeneity of intervention effect across the socioeconomic subsamples was first assessed to establish whether overall or separate subsample analyses were appropriate. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN99820519. Findings: We randomly assigned 4613 participants to the StopAdvisor group (n=2321) or the control group (n=2292); 2142 participants were of low socioeconomic status and 2471 participants were of high status. The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary (237 [10%] vs 220 [10%] participants; relative risk [RR] 1·06, 95% CI 0·89-1·27; p=0·49) and the secondary (358 [15%] vs 332 [15%] participants; 1·06, 0·93-1·22; p=0·37) outcomes; however, the intervention effect differed across socioeconomic status subsamples (1·44, 0·99-2·09; p=0·0562 and 1·37, 1·02-1·84; p=0·0360, respectively). StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website (primary outcome: 90 [8%] of 1088 vs 64 [6%] of 1054 participants; RR 1·36, 95% CI 1·00-1·86; p=0·0499; secondary outcome: 136 [13%] vs 100 [10%] participants; 1·32, 1·03-1·68, p=0·0267), but did not improve cessation rates in those with high socioeconomic status (147 [12%] of 1233 vs 156 [13%] of 1238 participants; 0·95, 0·77-1·17; p=0·61 and 222 [18%] vs 232 [19%] participants; 0·96, 0·81-1·13, p=0·64, respectively). Interpretation: StopAdvisor was more effective than an information-only website in smokers of low, but not high, socioeconomic status. StopAdvisor could be implemented easily and made freely available, which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support. Funding: National Prevention Research Initiative.

The Lancet. Respiratory medicine · randomised controlled trial · 99 citationsread the source →

Barriers and facilitators to chronic pain self-management: a qualitative study of primary care patients with comorbid musculoskeletal pain and depression.

Objective: To identify barriers and facilitators to self-management of chronic musculoskeletal pain among patients with comorbid pain and depression. Design: A qualitative study using focus group methodology. Setting: Veteran Affairs (VA) and University primary care clinics. Patients: Recruited after participation in a clinical trial. Intervention: The Stepped Care for Affective Disorders and Musculoskeletal Pain (SCAMP) trial tested an intervention of optimized antidepressant therapy combined with a pain self-management program versus usual care for primary care patients with comorbid chronic pain and depression. Outcome measures: Thematic content analysis from focus group data was used to identify patient-perceived barriers and facilitators to self-management of chronic musculoskeletal pain. Results: Patients (N = 18) were 27 to 84 years old (M = 54.8), 61% women, 72% white, and 22% black. Barriers to pain self-management included: 1) lack of support from friends and family; 2) limited resources (e.g., transportation, financial); 3) depression; 4) ineffectiveness of pain-relief strategies; 5) time constraints and other life priorities; 6) avoiding activity because of fear of pain exacerbation; 7) lack of tailoring strategies to meet personal needs; 8) not being able to maintain the use of strategies after study completion; 9) physical limitations; and 10) difficult patient-physician interactions. Facilitators to improve pain self-management included 1) encouragement from nurse care managers; 2) improving depression with treatment; 3) supportive family and friends; and 4) providing a menu of different self-management strategies to use. Conclusions: Future research is needed to confirm these findings and to design interventions that capitalize on the facilitators identified while at the same time addressing the barriers to pain self-management.

Pain medicine (Malden, Mass.) · cohort or longitudinal · 179 citationsread the source →

Changes in emotion regulation following cognitive-behavioral therapy for anxious youth.

This study examined emotion-related functioning following cognitive-behavioral therapy (CBT) with 37 youth with anxiety disorders (22 boys, 15 girls) ranging in age from 7 to 15 with a principal diagnosis of generalized anxiety disorder (n = 27), separation anxiety disorder (n = 12), and/or social phobia (n = 13). Treated youth exhibited a reduction in anxiety and increased anxiety self-efficacy and emotional awareness at posttreatment. Treated youth also demonstrated improved coping and less emotional dysregulation with worry but not with anger or sadness. The results suggest that the gains made in worry regulation do not generalize to other emotions that are not specifically targeted within the CBT protocol.

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53 · randomised controlled trial · 52 citationsread the source →

Weight loss improves reproductive outcomes in obese women undergoing fertility treatment: a randomized controlled trial.

For women attempting pregnancy, obesity reduces fertility and is an independent risk factor for obstetric and neonatal complications. The aim of this evaluator-blinded, randomized controlled trial was to evaluate a weight loss intervention on pregnancy rates in obese women undertaking fertility treatment. Forty-nine obese women, aged ≤ 37 years, presenting for fertility treatment were randomized to either a 12-week intervention (n = 27) consisting of a very-low-energy diet for the initial 6 weeks followed by a hypocaloric diet, combined with a weekly group multidisciplinary programme; or a control group (n = 22) who received recommendations for weight loss and the same printed material as the intervention. Anthropometric and reproductive parameters were measured at baseline and at 12 weeks. The 22 women who completed the intervention had greater anthropometric changes (-6.6 ± 4.6 kg and -8.7 ± 5.6 cm vs. -1.6 ± 3.6 kg and -0.6 ± 6.3 cm) compared with the control group (n = 17; P < 0.001). The intervention group achieved a pregnancy rate of 48% compared with 14% (P = 0.007), took a mean two fertility treatment cycles to achieve each pregnancy compared with four in the control group (P = 0.002), and had a marked increase in the number of live births (44% vs. 14%; P = 0.02). A group weight loss programme, incorporating dietary, exercise and behavioural components, is associated with a significant improvement in pregnancy rates and live births in a group of obese women undergoing fertility treatment.

Clinical obesity · randomised controlled trial · 84 citationsread the source →

A communication strategy and brochure for relatives of patients dying in the ICU.

Background: There is a need for close communication with relatives of patients dying in the intensive care unit (ICU). We evaluated a format that included a proactive end-of-life conference and a brochure to see whether it could lessen the effects of bereavement. Methods: Family members of 126 patients dying in 22 ICUs in France were randomly assigned to the intervention format or to the customary end-of-life conference. Participants were interviewed by telephone 90 days after the death with the use of the Impact of Event Scale (IES; scores range from 0, indicating no symptoms, to 75, indicating severe symptoms related to post-traumatic stress disorder [PTSD]) and the Hospital Anxiety and Depression Scale (HADS; subscale scores range from 0, indicating no distress, to 21, indicating maximum distress). Results: Participants in the intervention group had longer conferences than those in the control group (median, 30 minutes [interquartile range, 19 to 45] vs. 20 minutes [interquartile range, 15 to 30]; P<0.001) and spent more of the time talking (median, 14 minutes [interquartile range, 8 to 20] vs. 5 minutes [interquartile range, 5 to 10]). On day 90, the 56 participants in the intervention group who responded to the telephone interview had a significantly lower median IES score than the 52 participants in the control group (27 vs. 39, P=0.02) and a lower prevalence of PTSD-related symptoms (45% vs. 69%, P=0.01). The median HADS score was also lower in the intervention group (11, vs. 17 in the control group; P=0.004), and symptoms of both anxiety and depression were less prevalent (anxiety, 45% vs. 67%; P=0.02; depression, 29% vs. 56%; P=0.003). Conclusions: Providing relatives of patients who are dying in the ICU with a brochure on bereavement and using a proactive communication strategy that includes longer conferences and more time for family members to talk may lessen the burden of bereavement. (ClinicalTrials.gov number, NCT00331877.)

The New England journal of medicine · randomised controlled trial · 820 citationsread the source →

Randomized controlled trial of maintaining quality of life during radiotherapy for advanced cancer.

Background: Psychosocial interventions often address only 1 domain of quality of life (QOL), are offered to patients with early-stage cancer, do not include the caregiver, and are delivered after cancer treatment has been completed. Methods: In the current randomized controlled trial, 131 patients with advanced cancer who received radiotherapy and their caregivers were randomly assigned to either a 6-session, structured, multidisciplinary intervention arm or a standard care arm. The average age of the patients was 58 years, the majority were male (63%), and tumor types varied (gastrointestinal [37%], brain [22%], head and neck [16%], lung [13%], and other [12%]). The six 90-minute sessions addressed the 5 domains of QOL: cognitive, physical, emotional, social, and spiritual. The in-person intervention was followed by 10 brief telephone counseling sessions that took place over the next 6 months. Results: Of the 117 patients who completed the study, overall QOL (assessed by Functional Assessment of Cancer Therapy-General [FACT-G]) at week 4 was significantly higher in the intervention group (n = 54) compared with the standard arm control group (n = 63) (75.2 vs 68.7; P = .02). The 10 brief telephone contacts did not appear to impact QOL because at week 27 the groups had identical QOL (means of 77.6 and 77.7, respectively). There was no effect of the intervention noted on caregiver QOL. Conclusions: Participating in a 6-session multidisciplinary intervention was found to be effective in maintaining the QOL of patients with advanced cancer who were actively receiving radiotherapy. The QOL and symptom burden of this population is striking, making it important to identify effective QOL strategies to implement in conjunction with cancer care.

Cancer · randomised controlled trial · 91 citationsread the source →

Fronto-limbic and autonomic disjunctions to negative emotion distinguish schizophrenia subtypes.

Schizophrenia patients show a disconnection in amygdala-medial prefrontal cortex and autonomic arousal systems for processing fear. Concurrent functional magnetic resonance imaging [fMRI] and skin conductance recording were used to determine whether these disturbances are specific to fear, or present in response to other signals of danger. We also examined whether these disturbances distinguish a specific symptom profile. During scanning, 27 schizophrenia (13 paranoid, 14 nonparanoid) and 22 matched healthy control subjects viewed standardized facial expressions of fear, anger and disgust (versus neutral). Skin conductance responses [SCRs]were acquired simultaneously to assess phasic increases in arousal. 'With-arousal' versus 'without-arousal' responses were analysed using non-parametric methods. For controls, 'with-arousal' responses were associated with emotion-specific activity for fear (amygdala), disgust (insula) and anger (anterior cingulate), together with common medial prefrontal cortex [MPFC] engagement, as predicted. Schizophrenia patients displayed abnormally increased phasic arousal, with concomitant reductions in emotion-specific regions and MPFC. These findings may reflect a general disconnection between central and autonomic systems for processing signals of danger. This disjunction was most apparent in patients with a profile of paranoia, coupled with poor social function and insight. Heightened autonomic sensitivity to signals of fear, threat or contamination, without effective neural mechanisms for appraisal, may underlie paranoid delusions which concern threat and contamination, and associated social and interpersonal difficulties.

Psychiatry research · 116 citationsread the source →

The epidemiology of trauma and post-traumatic stress disorder in a representative cohort of young people in England and Wales.

Background: Despite the emphasis placed on childhood trauma in psychiatry, comparatively little is known about the epidemiology of trauma and trauma-related psychopathology in young people. We therefore aimed to evaluate the prevalence, clinical features, and risk factors associated with trauma exposure and post-traumatic stress disorder (PTSD) in young people. Methods: We carried out a comprehensive epidemiological study based on participants from the Environmental Risk Longitudinal Twin Study, a population-representative birth-cohort of 2232 children born in England and Wales in 1994-95. At the follow-up home visit at age 18 years, participants were assessed with structured interviews for trauma exposure, PTSD, other psychopathology, risk events, functional impairment, and service use. Risk factors for PTSD were measured prospectively over four previous assessments between age 5 and 12 years. The key outcomes were the prevalence, clinical features, and risk factors associated with trauma exposure and PTSD. We also derived and tested the internal validity of a PTSD risk calculator. Findings: We found that 642 (31·1%) of 2064 participants reported trauma exposure and 160 (7·8%) of 2063 experienced PTSD by age 18 years. Trauma-exposed participants had high rates of psychopathology (187 [29·2%] of 641 for major depressive episode, 146 [22·9%] of 638 for conduct disorder, and 102 [15·9%] of 641 for alcohol dependence), risk events (160 [25·0%] of 641 for self-harm, 53 [8·3%] of 640 for suicide attempt, and 42 [6·6%] of 640 for violent offence), and functional impairment. Participants with lifetime PTSD had even higher rates of psychopathology (87 [54·7%] of 159 for major depressive episode, 43 [27·0%] of 159 for conduct disorder, and 41 [25·6%] of 160 for alcohol dependence), risk events (78 [48·8%] of 160 for self-harm, 32 [20·1%] of 159 for suicide attempt, and 19 [11·9%] of 159 for violent offence), and functional impairment. However, only 33 (20·6%) of 160 participants with PTSD received help from mental health professionals. The PTSD risk calculator had an internally validated area under the receiver operating characteristic curve of 0·74, indicating adequate discrimination of trauma-exposed participants with and without PTSD, and internally validated calibration-in-the-large of -0·10 and calibration slope of 0·90, indicating adequate calibration. Interpretation: Trauma exposure and PTSD are associated with complex psychiatric presentations, high risk, and significant impairment in young people. Improved screening, reduced barriers to care provision, and comprehensive clinical assessment are needed to ensure that trauma-exposed young people and those with PTSD receive appropriate treatment. Funding: The Medical Research Council, the National Institute of Child Health and Development, the Jacobs Foundation, the Nuffield Foundation, the National Society for Prevention of Cruelty to Children, the Economic and Social Research Council, the National Institute for Health Research, MQ, and Canadian Institutes for Advanced Research.

The lancet. Psychiatry · cohort or longitudinal · 287 citationsread the source →

SARS-CoV-2 in Spanish Intensive Care Units: Early experience with 15-day survival in Vitoria.

Purpose: Community transmission of SARS-CoV-2 was detected in Spain in February 2020, with 216% intensive care unit (ICU) capacity expanded in Vitoria by March 18th, 2020. Methods: We identified patients from the two public hospitals in Vitoria who were admitted to ICU with confirmed infection by SARS-CoV-2. Data reported here were available in April 6th, 2020. Mortality was assessed in those who completed 15-days of ICU stay. Results: We identified 48 patients (27 males) with confirmed SARS-CoV-2. Median [interquartile range (IQR)] age of patients was 63 [51-75] years. Symptoms began a median of 7 [5-12] days before ICU admission. The most common comorbidities identified were obesity (48%), arterial hypertension (44%) and chronic lung disease (37%). All patients were admitted by hypoxemic respiratory failure and none received non-invasive mechanical ventilation. Forty-five (94%) underwent intubation, 3 (6%) high flow nasal therapy (HFNT), 1 (2%) extracorporeal membrane oxygenation (ECMO) and 22 (46%) required prone position. After 15 days, 14/45 (31%) intubated patients died (13% within one week), 10/45 (22%) were extubated, and 21/45 (47%) underwent mechanical ventilation. Six patients had documented super-infection. Procalcitonin plasma above 0.5μg/L was associated with 16% vs. 19% (p=0.78) risk of death after 7 days. Conclusion: This early experience with SARS-CoV-2 in Spain suggests that a strategy of right oxygenation avoiding non-invasive mechanical ventilation was life-saving. Seven-day mortality in SARS-CoV-2 requiring intubation was lower than 15%, with 80% of patients still requiring mechanical ventilation. After 15 days of ICU admission, half of patients remained intubated, whereas one third died.

Anaesthesia, critical care & pain medicine · cohort or longitudinal · 156 citationsread the source →

Change in non-abstinent WHO drinking risk levels and alcohol dependence: a 3 year follow-up study in the US general population.

Background: Alcohol dependence is often untreated. Although abstinence is often the aim of treatment, many drinkers prefer drinking reduction goals. Therefore, if supported by evidence of benefit, drinking reduction goals could broaden the appeal of treatment. Regulatory agencies are considering non-abstinent outcomes as efficacy indicators in clinical trials, including reduction in WHO drinking risk levels-very high, high, moderate, and low-defined in terms of mean ethanol consumption (in grams) per day. We aimed to study the relationship between reductions in WHO drinking risk levels and subsequent reduction in the risk of alcohol dependence. Methods: In this population-based cohort study, we included data from 22 005 drinkers who were interviewed in 2001-02 (Wave 1) and re-interviewed 3 years later (2004-05; Wave 2) in the US National Epidemiologic Survey on Alcohol and Related Conditions. Alcohol consumption (WHO drinking risk levels) and alcohol dependence (at least three of seven DSM-IV criteria in the previous 12 months) were assessed at both waves. We used logistic regression to test the relationship between change in WHO drinking risk levels between Waves 1 and 2, and alcohol dependence at Wave 2. Findings: At Wave 1, 2·5% (weighted proportion) of the respondents were very-high-risk drinkers, 2·5% were high-risk drinkers, 4·8% were moderate-risk drinkers, and most (90·2%) were low-risk drinkers. Reduction in WHO drinking risk level predicted significantly lower odds of alcohol dependence at Wave 2, particularly among very-high-risk drinkers (adjusted odds ratios 0·27 [95% CI 0·18-0·41] for reduction by one level, 0·17 [0·10-0·27] for two levels, and 0·07 [0·05-0·10] for three levels) and high-risk drinkers (0·64 [0·54-0·75] for one level and 0·12 [0·09-0·15] for two levels), and among those with alcohol dependence at Wave 1 (0·29 [0·15-0·57] for one level, 0·06 [0·04-0·10] for two levels, and 0·04 [0·03-0·06] for three levels in very-high-risk drinkers). Interpretation: Our results support the use of reductions in WHO drinking risk levels as an efficacy outcome in clinical trials. Because these risk levels can be readily translated into standard drink equivalents per day of different countries, the WHO risk levels could also be used internationally to guide treatment goals and clinical recommendations on drinking reduction. Funding: US National Institute on Alcohol Abuse and Alcoholism, New York State Psychiatric Institute, the Alcohol Clinical Trials Initiative.

The lancet. Psychiatry · cohort or longitudinal · 117 citationsread the source →

Clinical outcomes on B/F/TAF and dolutegravir-based regimens at 12 months following regimen switch: an observational cohort study.

Background: This retrospective observational study evaluated the clinical use and treatment outcomes in virologically suppressed people with HIV (PWH) switching to either bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)-based regimens (single- and multi-tablet formulations (STR and MTR)). Methods: We analyzed electronic medical and dispensing records from Trio Health HIV Research Network for treatment-experienced PWH ≥ 18 years suppressed (viral load [VL] < 200 copies/mL) at switch to B/F/TAF, DTG STR (DTG/3TC, DTG/RPV, DTG/3TC/ABC) or most common DTG MTRs with VL at 12 months (+/-3) since switch between April 2019 and December 2024. Univariate comparisons: chi-square or t-test; characteristics associated with virologic suppression at 12 months: multivariable logistic regression [LR], controlling for age, gender, race, baseline CD4 count, regimen, and adherence (proportion days covered [PDC] ≥ 80%). Results: Of 3141 PWH, 66% switched to B/F/TAF, 27% to DTG STR, and 7% to DTG MTRs. Baseline characteristics differed significantly between groups: B/F/TAF group had a higher proportion of males (81% vs. 67% DTG MTR) and Black individuals (40% vs. 31% DTG STR), while the DTG STR and MTR groups had higher proportions of PWH with cardiovascular disease (35% and 39% respectively vs. 32% on B/F/TAF) and eGFR < 60 mL/min/1.73 m² (18% and 22% respectively vs. 8% on B/F/TAF). At 12 months post switch, proportion of individuals with PDC ≥ 80% was higher in the DTG STR group (76%) compared to DTG MTR (67%) and B/F/TAF (69%) with similar virologic suppression across groups (98%, 98%, and 97% respectively). In multivariable LR, there was an association of White race, PDC ≥ 80%, and CD4 ≥ 200 cells/mm3 with greater probability of suppression at 12 months. Conclusions: Despite differences in baseline characteristics and regimen adherence between individuals switched to B/F/TAF, DTG STRs, and MTRs, both B/F/TAF and DTG-based regimens were associated with high rates of virologic suppression. This data strongly supports the inclusion of these simple and safe regimens as switch options in virologically suppressed PWH. Baseline differences in patient demographics and characteristics may have impacted the adherence on B/F/TAF compared to DTG STR, however virologic outcomes were preserved, demonstrating the forgiveness of B/F/TAF in populations potentially facing adherence challenges.

AIDS research and therapy · cohort or longitudinalread the source →

Structure provided by parents in middle childhood predicts cortisol reactivity in adolescence among the offspring of parents with bipolar disorder and controls.

Recent studies suggest that childhood exposure to adversity influences later functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Parenting style in childhood, a putative moderator of adversity, may be important in determining HPA reactivity in adolescence. As part of a prospective, longitudinal study, saliva was collected at awakening and 30 and 60 min later over 2 days among 27 offspring of parents with bipolar disorder (high risk; 16.7+/-1.5 years) and 26 offspring of parents with no mental disorders (low risk; 16.2+/-1.7 years). In addition, 24 of the high risk and 22 of the low risk adolescents completed the "Trier Social Stress Test" (TSST). Parents had rated their parenting style when their offspring were 6-13 years of age. Low levels of structure (i.e. organization and consistency) provided by parents in middle childhood were predictive of an elevated cortisol response following awakening (beta=-0.36; p<0.05) and during the TSST (beta=-0.33; p<0.05), even while controlling for risk group. These associations were independent of other indices of environmental risk, and of adolescents' mood and behavior. The level of structure provided by parents in childhood predicted independent measures of cortisol reactivity in adolescence, suggesting that parenting style may regulate different aspects of HPA reactivity.

Psychoneuroendocrinology · clinical trial · 42 citationsread the source →

Clinical trial: long-term use of proton pump inhibitors in primary care patients - a cross sectional analysis of 901 patients.

Background: The use of proton pump inhibitors (PPIs) is extensive. While the incidence of new treatments remains stable, the prevalence of long-term treatment is rising. Studies have shown that up to 70% of patients on chronic acid suppression lack a verified indication for treatment. Aims: To investigate primary care patient characteristics associated with long-term use of PPIs. Methods: A cross-sectional analysis of 42,634 patients registered with 22 general practitioners was performed. Patients with prescriptions of > or =120 tablets/year were defined as long-term users. A survey of a subgroup of patients without verified indication was performed. Results: In all, 901 (2.1%) patients were long-term treated. Verified indications for treatment were identified for 247/901 (27%). An upper GI endoscopy had been performed in 418 patients (46%). Of the 194/654 without verified indication who participated in the survey, 71% reported heartburn/acid regurgitation as the reason for therapy. On-demand therapy was reported by 43/194 (22%) and previous attempts to withdraw by 119/194 (61%). Conclusions: The prevalence of PPI long-term treatment among primary care patients is 2.1%. The main reason for treatment is reflux symptoms or verified GERD. Rationalization of use of PPIs is possible as daily treatment without attempts to discontinue is frequently observed.

Alimentary pharmacology & therapeutics · clinical trial · 24 citationsread the source →

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

Background: We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Methods: Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Results: Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). Conclusions: nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients.

Cephalalgia : an international journal of headache · clinical trial · 140 citationsread the source →

Availability, use of, and satisfaction with green space, and children's mental wellbeing at age 4 years in a multicultural, deprived, urban area: results from the Born in Bradford cohort study.

Background: It is unknown whether the quantity or quality of green space is more important for mental wellbeing. We aimed to explore associations between availability of, satisfaction with, and use of green space and mental wellbeing among children aged 4 years in a multi-ethnic sample. Methods: We did a 4-year follow-up assessment of participants in the Born in Bradford longitudinal cohort study, which recruited children and mothers at the city's main maternity unit from 2007 to 2011. The primary outcome was parent-reported mental wellbeing for children aged 4 years, assessed with the standardised Strengths and Difficulties Questionnaire. Total, internalising, and externalising behavioural difficulties and prosocial behaviour scales were computed (with higher scores indicating greater difficulties or more prosocial behaviour). Residential green space around participants' home addresses and distance to major green spaces were computed with the normalised difference vegetation index (NDVI). A subsample of participants completed additional questionnaires on measures of satisfaction with, and use of, local green spaces. Multiple regressions examined associations between green space and children's mental wellbeing and explored moderation by ethnicity (white British vs south Asian) and socioeconomic status. Findings: Between Oct 1, 2012, and June 30, 2015, 2594 mothers attended a follow-up appointment during which they completed a detailed questionnaire assessing the health of their child. 1519 (58%) participants were of south Asian origin, 740 (29%) of white British origin, and 333 (13%) of another ethnicity. Data on ethnicity were missing for two participants. 832 (32%) of 2594 participants completed additional questionnaires. Ethnicity moderated associations between residential green space and mental wellbeing (p<0·05 for total and internalising difficulties). After adjusting for all relevant variables, more green space was associated with fewer internalising behavioural difficulties (mean NDVI 100 m: β -2·35 [95% CI -4·20 to -0·50]; 300 m: -3·15 [-5·18 to -1·13]; 500 m: -2·85 [-4·91 to -0·80]) and with fewer total behavioural difficulties (100 m: -4·27 [-7·65 to -0·90]; 300 m: -5·22 [-8·91 to -1·54]; 500 m: -4·82 [-8·57 to -1·07]) only for south Asian children across all three buffer zones. In the subsample of participants, the effect of NDVI on wellbeing was rendered non-significant after controlling for satisfaction with, and use of, green space. Among south Asian children, satisfaction with green space was significantly associated with fewer total behavioural difficulties across all three buffer zones (β -0·59 [95% CI -1·11 to -0·07]), fewer internalising behavioural difficulties within 100 m (-0·28 [95% CI -0·56 to -0·003]) and 300 m buffer zones (-0·28 [-0·56 to -0·002]), and greater prosocial behaviour across all three buffer zones (0·20 [0·02 to 0·38]); no such associations were observed among white British children. Interpretation: Positive effects of green space on wellbeing differ by ethnicity. Satisfaction with the quality of green space appears to be a more important predictor of wellbeing than does quantity of green space. Public health professionals and urban planners need to focus on both quality and quantity of urban green spaces to promote health, particularly among ethnic minority groups. Funding: European Community's Seventh Framework Programme.

The Lancet. Planetary health · 61 citationsread the source →

Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

Unlabelled: The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. Methods: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. Results: Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. Conclusion: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.

Respiratory medicine · cohort or longitudinal · 199 citationsread the source →

Human-Centered Design Approaches in Digital Mental Health Interventions: Exploratory Mapping Review.

Background: Digital mental health interventions have a great potential to alleviate mental illness and increase access to care. However, these technologies face significant challenges, especially in terms of user engagement and adoption. It has been suggested that this issue stems from a lack of user perspective in the development process; accordingly, several human-centered design approaches have been developed over the years to consider this important aspect. Yet, few human-centered design approaches to digital solutions exist in the field of mental health, and rarely are end users involved in their development. Objective: The main objective of this literature review is to understand how human-centered design is considered in e-mental health intervention research. Methods: An exploratory mapping review was conducted of mental health journals with the explicit scope of covering e-mental health technology. The human-centered design approaches reported and the core elements of design activity (ie, object, context, design process, and actors involved) were examined among the eligible studies. Results: A total of 30 studies met the inclusion criteria, of which 22 mentioned using human-centered design approaches or specific design methods in the development of an e-mental health solution. Reported approaches were classified as participatory design (11/27, 41%), codesign (6/27, 22%), user-centered design (5/27, 19%), or a specific design method (5/27, 19%). Just over half (15/27, 56%) of the approaches mentioned were supported by references. End users were involved in each study to some extent but not necessarily in designing. About 27% (8/30) of all the included studies explicitly mentioned the presence of designers on their team. Conclusions: Our results show that some attempts have indeed been made to integrate human-centered design approaches into digital mental health technology development. However, these attempts rely very little on designers and design research. Researchers from other domains and technology developers would be wise to learn the underpinnings of human-centered design methods before selecting one over another. Inviting designers for assistance when implementing a particular approach would also be beneficial. To further motivate interest in and use of human-centered design principles in the world of e-mental health, we make nine suggestions for better reporting of human-centered design approaches in future research.

JMIR mental health · review · 61 citationsread the source →