Which intervention is better for malaria vector control: insecticide mixture long-lasting insecticidal nets or standard pyrethroid nets combined with indoor residual spraying?

BACKGROUND: Malaria control today is threatened by widespread insecticide resistance in vector populations. The World Health Organization (WHO) recommends the use of a mixture of unrelated insecticides for indoor residual spraying (IRS) and long-lasting insecticidal nets (LNs) or as a combination of interventions for improved vector control and insecticide resistance management. Studies investigating the efficacy of these different strategies are necessary. METHODS: The efficacy of Interceptor® G2 LN, a newly developed LN treated with a mixture of chlorfenapyr (a pyrrole) and alpha-cypermethrin (a pyrethroid), was compared to a combined chlorfenapyr IRS and Interceptor® LN (a standard alpha-cypermethrin LN) intervention in experimental huts in Cove Southern Benin, against wild, free-flying, pyrethroid-resistant Anopheles gambiae s.l. A direct comparison was also made with a pyrethroid-only net (Interceptor® LN) alone and chorfenapyr IRS alone. RESULTS: WHO resistance bioassays performed during the trial demonstrated a pyrethroid resistance frequency of >90% in the wild An. gambiae s.l. from the Cove hut site. Mortality in the control (untreated net) hut was 5%. Mortality with Interceptor® LN (24%) was lower than with chlorfenapyr IRS alone (59%, P < 0.001). The combined Interceptor® LN and chlorfenapyr IRS intervention and the mixture net (Interceptor® G2 LN) provided significantly higher mortality rates (73 and 76%, respectively) and these did not differ significantly between both treatments (P = 0.15). Interceptor LN induced 46% blood-feeding inhibition compared to the control untreated net, while chlorfenapyr IRS alone provided none. Both mixture/combination strategies also induced substantial levels of blood-feeding inhibition (38% with combined interventions and 30% with Interceptor® G2 LN). A similar trend of improved mortality of pyrethroid-resistant An. gambiae s.l. from Cove was observed with Interceptor® G2 LN (79%) compared to Interceptor LN (42%, P < 0.001) in WHO tunnel tests. CONCLUSION: The use of chlorfenapyr and alpha-cypermethrin together as a mixture on nets (Interceptor® G2 LN) or a combined chlorfenapyr IRS and pyrethroid LN intervention provides improved control of pyrethroid-resistant malaria vectors by inducing significantly higher levels of mortality through the chlorfenapyr component and providing personal protection through the pyrethroid component. Both strategies are comparable in their potential to improve the control of malaria transmitted by pyrethroid resistant mosquito vectors

Online psychotherapy: trailblazing digital healthcare

Advances in digital technology have a profound impact on conventional healthcare systems. We examine the trailblazing use of online interventions to enable autonomous psychological care which can greatly enhance individual- and population-level access to services. There is strong evidence supporting online cognitive–behavioural therapy and more engaging programmes are now appearing so as to reduce user ‘attrition’. The next generation of autonomous psychotherapy programmes will implement adaptive and personalised responses, moving beyond impersonalised advice on cognitive and behavioural techniques. This will be a more authentic form of psychotherapy that integrates therapy with the actual relationship experiences of the individual user

Connecting brain and body: transdiagnostic relevance of connective tissue variants to neuropsychiatric symptom expression

The mind is embodied; thoughts and feelings interact with states of physiological arousal and physical integrity of the body. In this context, there is mounting evidence for an association between psychiatric presentations and the expression variant connective tissue, commonly recognised as joint hypermobility. Joint hypermobility is common, frequently under-recognised, significantly impacts quality of life, and can exist in isolation or as the hallmark of hypermobility spectrum disorders (encompassing joint hypermobility syndrome and hypermobile Ehlers-Danlos syndrome). In this narrative review, we appraise the current evidence linking psychiatric disorders across the lifespan, beginning with the relatively well-established connection with anxiety, to hypermobility. We next consider emerging associations with affective illnesses, eating disorders, alongside less well researched links with personality disorders, substance misuse and psychosis. We then review related findings relevant to neurodevelopmental disorders and stress-sensitive medical conditions. With growing understanding of mind-body interactions, we discuss potential aetiopathogenetic contributions of dysautonomia, aberrant interoceptive processing, immune dysregulation and proprioceptive impairments in the context of psychosocial stressors and genetic predisposition. We examine clinical implications of these evolving findings, calling for increased awareness amongst healthcare professionals of the transdiagnostic nature of hypermobility and related disorders. A role for early screening and detection of hypermobility in those presenting with mental health and somatic symptoms is further highlighted, with a view to facilitate preventative approaches alongside longer-term holistic management strategies. Finally, suggestions are offered for directions of future scientific exploration which may be key to further delineating fundamental mind-body-brain interactions

Neurovisceral phenotypes in the expression of psychiatric symptoms

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brainbody mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in 'emotional' brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognised factors causing vasodilatation (as noted post prandially, post exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety

Hypermobility in patients with functional seizures: toward a pathobiological understanding of complex conditions

Background: Functional seizures (FS), otherwise known as psychogenic nonepileptic seizures (PNES), are a common symptom presenting to neurology and epilepsy clinics. There is a pressing need for further research to understand the neurobiology of FS to develop mechanistically targeted treatments. Joint hypermobility is an expression of variation in connective tissue structure along a spectrum, and it has received increasing attention in functional neurological disorders, but there is lack of evidence of its relevance in FS. Methods: In the present study, forty-two patients with FS and a non-clinical comparison group of 34 age/sex-matched controls were recruited. Joint hypermobility of all participants was quantified using the Beighton scale. Results: In our sample, 24 (57%) patients with FS, and 7 (21%) of the comparison group met criteria for joint hypermobility (p = 0.002). Our statistical model revealed that patients with FS showed a significant degree of hypermobility compared to the comparison group (odds ratio = 11.1; Confidence interval: 2.1–78.0, p = 0.008), even after controlling age, sex, anxiety, and depression. Conclusion: We found a significant association between FS and joint hypermobility, which was independent of anxiety and depression

Subjective embodiment during the rubber hand illusion predicts severity of premonitory sensations and tics in Tourette Syndrome

In Tourette Syndrome, the expression of tics and commonly preceding premonitory sensations is associated with perturbed subjective feelings of self-control and agency. We compared responses to the Rubber Hand Illusion in 23 adults with TS and 22 controls. Both TS and control participants reported equivalent subjective embodiment of the artificial hand: feelings of ownership, location, and agency were greater during synchronous visuo-tactile stimulation, compared to asynchronous. However, individuals with TS did not manifest greater proprioceptive drift, an objective marker of embodiment observed in controls. An 'embodiment prediction error' index of the difference between subjective embodiment and objective proprioceptive drift correlated with severity of premonitory sensations. Feelings of ownership also correlated with premonitory sensation severity, and feelings of agency with tic severity. These findings suggest that subjective bodily ownership, as measured by the rubber hand illusion, contributes to susceptibility to the premonitory sensations that may be a precipitating factor in tics

Variant connective tissue (joint hypermobility) and its relevance to depression and anxiety in adolescents: a cohort-based case-control study

Objective: To test whether variant connective tissue structure, as indicated by the presence of joint hypermobility, poses a developmental risk for mood disorders in adolescence. Design: Cohort-based case-control study. Setting: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were interrogated. Participants: 6105 children of the ALSPAC cohort at age 14 years old, of whom 3803 also were assessed when aged 18 years. Main outcome measures: In a risk analysis, we examined the relationship between generalised joint hypermobility (GJH) at age 14 years with psychiatric symptoms at age 18 years. In an association analysis, we examined the relationship between presence of symptomatic joint hypermobility syndrome (JHS) and International Classification of Diseases (ICD-10) indication of depression and anxiety (Clinical Interview Schedule Revised [CIS-R], Anxiety Sensitivity Index [ASI]) at age 18 years. Results: GJH was more common in females (n=856, 28%) compared to males (n=319, 11%; OR 3.20 (95% CI 2.78 to 3.68); P<0.001). In males only, GJH at age 14 years was associated with depression at 18 years (OR 2.10 (95%CI 1.17 to 3.76); P=0.013). An index of basal physiological arousal, elevated resting heart rate, mediated this effect. Across genders, the diagnosis of JHS at age 18 years was associated with the presence of depressive disorder (adjusted OR 3.53 (95%CI 1.67 to 7.40); P=0.001), anxiety disorder (adjusted OR 3.14 (95% CI 1.52 to 6.46); P=0.002), level of anxiety (B=8.08, t(3278)=3.95; P<0.001), and degree of psychiatric symptomatology (B=5.89, t(3441)=0.093; p<0.001). Conclusions: Variant collagen, indexed by joint hypermobility, is linked to the emergence of depression and anxiety in adolescence, an effect mediated by autonomic factors in males. Recognition of this association may motivate further evaluation, screening, and interventions to mitigate development of psychiatric disorders and improve health outcomes

Variant connective tissue (joint hypermobility) and dysautonomia are associated with multimorbidity at the intersection between physical and psychological health

The symptoms of joint hypermobility extend beyond articular pain. Hypermobile people commonly experience autonomic symptoms (dysautonomia), and anxiety or related psychological issues. We tested whether dysautonomia might mediate the association between hypermobility and anxiety in adults diagnosed with mental health disorders and/or neurodevelopmental conditions (hereon referred to as patients), by quantifying joint hypermobility and symptoms of autonomic dysfunction. Prevalence of generalized joint laxity (hypermobility) in 377 individuals with diagnoses of mental health disorders and/or neurodevelopmental conditions was compared to prevalence recorded in the general population. Autonomic symptom burden was compared between hypermobile and non-hypermobile patients. Mediation analysis explored relationships between hypermobility, autonomic dysfunction, and anxiety. Patient participants had elevated prevalence of generalized joint laxity (38%) compared to the general population rate of 19% (odds ratio: 2.54 [95% confidence interval: 2.05, 3.16]). Hypermobile participants reported significantly more autonomic symptoms. Symptoms of orthostatic intolerance mediated the relationship between hypermobility and diagnosis of an anxiety disorder. Patients with mental health disorders and/or neurodevelopmental conditions have high rates of joint hypermobility. Accompanying autonomic dysfunction mediates the association between joint hypermobility and clinical anxiety status. Increased recognition of this association can enhance mechanistic understanding and improve the management of multimorbidity expressed in physical symptoms and mental health difficulties

Altering Dynamics of Autonomic Processing Therapy (ADAPT) trial: a novel, targeted treatment for reducing anxiety in joint hypermobility

Background Hypermobility is a poorly recognised and understood musculoskeletal disorder thought to affect around 20% of the population. Hypermobility is associated with reduced physiological and psychological functioning and quality of life and is a known risk factor for the development of an anxiety disorder. To date, no evidence-based, targeted treatment for anxiety in the context of hypermobility exists. The present intervention (ADAPT—Altering Dynamics of Autonomic Processing Therapy) is a novel therapy combining bio-behavioural training with cognitive approaches from clinical health psychology targeting the catastrophisation of internal sensations, with aim to improve autonomic trait prediction error. Method Eighty individuals with diagnosed hypermobility will be recruited and the efficacy of ADAPT to treat anxiety will be compared to an Emotion-Focused Supportive Therapy (EFST) comparator therapy in a randomised controlled trial. The primary treatment target will be post therapy score on the Beck Anxiety Inventory, and secondary outcomes will also be considered in relation to interoception, depression, alexithymia, social and work adjustment, panic symptoms and dissociation. Due to COVID restrictions, the intervention will be moved to online delivery and qualitative assessment of treatment tolerance to online therapy will also be assessed. Discussion Online delivery of an intervention targeting anxiety would improve the quality of life for those experiencing anxiety disorder and help to reduce the £11.7 billion that anxiety disorders cost the UK economy annually. Trial registration World Health Organization ISRCTN17018615. Registered on 20th February 2019; trial protocol version